General Principles

The neurocognitive history begins from the moment the patient is referred. The information provided in a referral may include the following:

Mode of referral: urgency, triggers for referral

Presenting symptoms

Longitudinal course: acute, subacute, gradual, fluctuating, progressive

Medical or psychiatric history

Investigations with positive or negative findings

The referral question

The neurocognitive history begins with the events precipitating the referral or assessment, particularly the first symptom of change, an understanding of gross functional capacity, and a sense of the longitudinal course of symptoms. From this basic “sketch” of an individual’s function, more specific questions can be directed toward specific cognitive domains; the presence or absence of neurobehavioral symptoms or signs; an individual’s capacity to function in social, occupational, and interpersonal roles; and relevant previous and related history.

Informant History

Although the key informant is usually a relative or caretaker, the clinician should seek information from as wide a range of sources as possible. Key informants may include a nursing home worker, neighbor, friend, or primary care physician. Such information may be crucial if the validity of the patient’s history is limited by impairments in insight regarding the nature of their deficits.

The patient and the informant should be interviewed separately, if possible. Informants are most likely to provide a full and frank history when interviewed alone. Caretakers may not wish to disclose the extent of their concerns with the patient present, for fear of distressing him or her. This is especially relevant if caretakers have not discussed their concerns with the patient or if the content of their concerns is experienced as a betrayal of trust, which in extreme circumstances may put the caretaker at risk.

Patient History

The content of the history provided by the patient is meaningful, because many patients are aware of their difficulties to a degree and may proffer a straightforward problem list. Equally revealing is the patient who is seemingly unaware of any difficulties and denies problems as a result of cognitive impairments or psychiatric disturbance. Most patients respond well to an open-ended question about their presentation, such as “What is your understanding of why you are seeing me today?” In some circumstances, it is also appropriate to reveal the concerns of others: for example, “I understand that you have been having difficulties with your memory recently.”

The process of the provision of historical information may be equally revealing. Patients may betray language difficulties through word-finding problems, psychosis through thought disorder, depressed mood through a lengthy latency in response time, or executive impairment through an empty or concrete account of events.

Integration of Neurobehavioral and Neurocognitive History

Neurobehavioral disturbances such as depression or psychosis are often the initial presenting feature in patients with neurocognitive impairment. Conversely, patients who initially present with the neurocognitive features of dementia may later exhibit psychotic symptoms; disinhibited, stereotypical, or inappropriate behavior; or mood and anxiety disturbance.¹⁰ Psychiatric disorders with associated behavioral disturbance may themselves manifest with neurocognitive impairments, such as the difficulties with sustained attention, memory, and processing speed seen in major depression¹¹ or the working memory impairments seen in schizophrenia.¹² Neurobehavioral impairment may herald future neurocognitive impairment, and vice versa. For example, frontotemporal dementias commonly manifest with neurobehavioral disturbance,¹³ and late-life depression may herald Alzheimer’s disease.¹⁴

Assessment Trigger

Assessment may be triggered by a critical event such as a patient’s putting himself or herself at risk or endangering others or such as significant interpersonal conflict. The nature of such a critical event may provide useful information about the type of disturbance and its onset but, perhaps more important, the nature guides future management through emphasis of issues such as safety, competence, and suitability of placement. A similar situation can occur when a patient’s environment is radically changed, such as a residential shift from a highly structured environment to a less structured one, or the loss of a crucial source of support, such as with the illness or death of a spouse. A gradually developing impairment may, however, manifest abruptly when it reaches a critical threshold for caretakers or relatives whose capacity to accommodate the deficits of the patient has been exhausted.

Evolution of Symptoms

The longitudinal course of illness is most commonly established through informants, and a complete history may need to be obtained from a number of sources. The nature of the onset of symptoms and the context in which they occur may be diagnostically discriminatory. For example, delirium usually manifests rapidly over a couple of days in the context of significant medical insult, whereas neurocognitive impairment associated with a central nervous system (CNS) neoplasm usually manifests over a few months, frequently in concert with other neurological symptoms. Many caretakers of patients with a dementing illness report subtle and insidious changes occurring for a year or more before assessment. Exceptions to this may occur, such as a subacute delirium or a rapidly progressive dementia. The longitudinal course may allow diagnostic differentiation particularly within the dementias. Alzheimer’s disease and frontotemporal dementias usually show gradual progression, whereas the time course of vascular dementia is often, but not always, stepwise. Rapid cognitive decline is suggestive of a prion dementia or a potentially reversible cause such as vasculitis or neoplasia.

The sequence of symptoms can be similarly informative. Depressed mood and neurovegetative disturbance for 3 months before the onset of memory problems are likely to indicate a depressive “pseudodementia.” An initial presentation of apathy, disinhibition, or stereotypical behaviors before memory or language impairment are suggestive of a frontotemporal dementia, whereas impaired new learning as the first symptom would be more suggestive of an Alzheimer’s-type dementia.

The age at symptom onset may narrow the list of differential diagnoses. Cognitive impairment in early adult life may be associated with adult-onset forms of inherited metabolic disorders, such as leukodystrophies, but are more frequently associated with potentially reversible causes of impairment, such as CNS infections, inflammatory disorders, or neoplasia. When impairment manifests in the fourth through sixth decades, earlyonset dementias, such as frontotemporal dementia or familial Alzheimer’s disease, or the early manifestation of undiagnosed vascular disease should be considered. In later decades, most such illnesses are vascular or degenerative.

Finally, the presence of fluctuations in the mental state and functioning may provide clues to etiology. Fluctuations in the level of arousal and orientation over days are seen in delirium. Late afternoon and early evening deteriorations may reflect the “sundowning” seen in dementias, whereas episodes of undiagnosed confusion occurring over a number of months may point to a diagnosis of Lewy body dementia.

Gross Functional Capacity

Patients and caretakers do not always have a specific complaint of “cognitive impairment.” Functional impairment as noticed by caretakers, relatives, or colleagues is commonly a precipitant for assessment. A thorough history of the pattern and nature of functional impairment provides valuable diagnostic information and may help treatment planning (Table 1-1).

TABLE 1-1 Evaluation of Functional Impairment

Neurocognitive Baseline

An understanding of an individual’s premorbid neurocognitive function allows an estimate of the degree and rate of decline. In impaired individuals with superior premorbid intellect, cross-sectional assessment may be within accepted norms for age. Commonly used screening instruments such as the Mini-Mental State Examination (MMSE) have a significant ceiling effect (see Chapter 2 on neuropsychological assessment) and are likely to be insensitive to this decline.¹⁵ Conversely, individuals with long-standing premorbid intellectual impairment may be incorrectly classified as suffering a degenerative process such as dementia, when in fact their neurocognitive function is stable.

Baseline function can be estimated grossly from the patient’s maximal educational and occupational attainment and from mental state features such as vocabulary and capacity for abstract thinking. A number of assessment tools for estimating premorbid intellectual function have been devised and rely on the stability of semantic language functions independent of disease or age. The most well-known and widely used is the National Adult Reading Test.¹⁶ This probes reading ability for irregular words, which has been shown to be relatively preserved in many disorders.¹⁷ Other similar tools include the Wechsler Test of Adult Reading¹⁸ and the Cambridge Contextual Reading Test.¹⁹ This issue is also addressed in Chapter 2 on neuropsychological assessment.

Attention and Orientation

Attention is not a unitary construct. Sustained, directed attention is the ability to attend to a specific stimulus without being distracted by extraneous internal or environmental stimuli. Other aspects of attention include the ability to share attention between simultaneous tasks (divided attention), the ability to switch attention between tasks, and the ability to attend to stimuli at different spatial locations. Disturbance of sustained, directed attention is most commonly reported in delirium (see Chapter 11) but may also be present with anxiety or mood disturbance, executive dysfunction (see Chapter 7), or dementias. Orientation is a more complex function involving the capacity to attend to stimuli and to process and retain information regarding locale and point in time.

The following questions are useful guides to areas for evaluation:

Can the patient attend to, and persevere with, most tasks, or does the patient demonstrate difficulties completing a task or take much longer than would be expected (a measure of sustained, directed attention)?

Can the patient attend to the television or to reading of a newspaper article, a magazine, or a book (sustained, directed attention)?

Can the patient ignore distractions?

Can the patient converse while doing something else (a measure of divided attention)?

Is the patient aware of the time of day or day of the week, and does he or she act accordingly with regard to mealtimes or daily tasks?

Language

Language is the basic tool of human communication and a basic component of many cognitive abilities. Language functions are commonly ascribed to the dominant hemisphere, and because cerebral dominance for language is closely allied to handedness, it is useful to be aware of the patient’s handedness before language function is assessed. Most of the conditions that produce disorders of language affect the left hemisphere and are commonly of vascular, traumatic, neoplastic, or degenerative origin.

Disorders of language are separated into aphasia (partial or total inability to articulate ideas or comprehend spoken or written language), alexia (inability to read), and agraphia (inability to write). An understanding of the large group of aphasias has been complicated by various nomenclatures, although the most recognized is that originally proposed by Benson and Geschwind,²⁰ which divides the group into Broca’s, Wernicke’s, global, conduction, anomic, and transcortical aphasias. This is discussed in more detail in Chapter 3.

The following questions are useful guides to areas for evaluation:

Has the patient had any difficulties with speech, such as in finding the right word or using the wrong word?

Can the patient pronounce words correctly, or does he or she make errors in pronunciation? Are these errors consistent?

Has there been a change in the patient’s grammar or sentence construction?

Has there been any reduction in the patient’s quantity or fluency of speech or in how much detail he or she provides in relating events?

Has the patient had difficulties in understanding or following conversation?

Does the patient miss the “gist” of the conversation? Does he or she misunderstand jokes or puns?

Does the patient’s speech jump about from idea to idea or drift off the topic?

Has there been a change in the amount, legibility, quality, sophistication, or size of the patient’s handwriting?

Visuospatial Functions

Visuospatial functions allow persons to orient themselves in space, enable safe locomotion, facilitate interaction with other individuals and objects, and allow for the expression and understanding of visual symbols of communication. Such functions are often related to pathology affecting the parietal cortex, which also contains contralateral motor and sensory representations of the body soma. Many disorders or diseases that disturb visuospatial functions are associated with significant motor or sensory impairment.

Visuospatial disturbance is common in dementias of all types, but it is most commonly seen with Alzheimer’s-type dementia. It is the presenting and dominant feature in the posterior variant, posterior cortical atrophy. Vascular or other acquired focal lesions of the parietal regions may also manifest with visuospatial difficulties. Aspects of visuoperceptual disturbance are discussed further in Chapter 5.

The following questions are useful guides to areas for evaluation:

Is the patient able to dress himself or herself appropriately? Does he or she wear items of clothing the wrong way around, inside out, or fitted incorrectly? Of importance, however, is that often a dressing apraxia may result from visuoperceptual disturbances or spatial inattention.

Can the patient find his or her way around the house, to the shops, and in unfamiliar environments when directions are provided?

Can the patient still use everyday objects—eating utensils, grooming items (toothbrush, comb), or tools of his or her trade—appropriately?

Can the patient tell the time from an analog clock or watch?

Can the patient use more complicated household items, such as an oven, washing machine, television, video recorder, or compact disc player? Disturbances of these functions may also arise from various forms of apraxia.

Does the patient ever get left and right mixed up?

Does the patient seem to ignore one side of his or her body when bathing, shaving, or dressing or one side of his or her environment when eating, walking/driving, or interacting socially?

Memory

Anterograde episodic memory is a general term for the registration, acquisition, storage, and subsequent retrieval of new information. Anterograde episodic memory impairment is perhaps the most common manifestation of neurocognitive disturbance. Anterograde episodic memory consists of several stages, beginning with the reception and registration of the information by a sensory modality, followed by the holding of the information temporarily in working memory (defined as the current content of consciousness); then storage in a more permanent form, which is enhanced by association with other already stored information and augmented by practice or rehearsal; and, finally, the process of retrieval. Each of these steps requires the integrity of the preceding steps, and any interruption in this hierarchy may disrupt anterograde episodic memory function. A detailed discussion of the various memory systems and their disorders is presented in Chapter 4.

Patients with dementia, particularly Alzheimer’s disease and vascular dementias, usually present to clinicians with memory disturbance before the onset of other neurocognitive or neurobehavioral disturbances. Memory impairment occurs commonly in brain disorders acquired from such causes as traumatic injury, postinfection states, and chronic exposure to CNS toxins such as alcohol.

The following questions are useful guides to areas for evaluation:

Can the patient recall recent conversations and accurately relate recent family news?

Is the patient able to describe or relate recent world or local events that may have been heard on the radio, seen on television, or read in the newspaper?

Has the patient missed birthdays, anniversaries, or other special events?

Does the patient tend to relate events or occasions from the more distant past when questioned about, or discussing in conversation, more recent events?

Has the patient had difficulties recalling the names of people, places, or things?

Executive Function

Executive functions are a group of complex functions that are based on the interaction with and executive control of basic processes such as attention, memory, and language. The prefrontal lobes and connected subcortical structures are crucial to the integrity of executive function, personality, and behavior. Cognitive functions that have been attributed to these networks include adaptive behavior, abstract conceptual ability, set-shifting/mental flexibility, problem-solving, planning, initiation, sequencing of behavior, and personality factors such as drive, motivation, and inhibition. Patients with the dysexecutive syndrome fail to anticipate changes, show poor planning ability, and do not learn from their errors. They are poor at self-guided learning and goal-setting, in that they perform normally on externally driven tasks but are poor at self-motivated tasks. Such patients are sensitive to interference from irrelevant stimuli, and may display both motor and cognitive perseveration. A more detailed overview of executive function and dysfunction can be found in Chapter 7.

Disorders that commonly manifest with executive dysfunction include frontotemporal dementias, traumatic brain injury, chronic alcohol abuse, and focal disease caused by vascular lesions or neoplasms. Of importance, but not as well recognized, is that patients with schizophrenia may exhibit subtle but often disabling disturbances of executive dysfunction.

The following questions are useful guides to areas for evaluation:

Has the patient shown a “personality change”?

Has there been any decline in appropriate social judgment, such as inappropriate familiarity with strangers or disinhibited sexual or aggressive behavior? Of note is that not all patients with executive dysfunction display these features.

Has there been any change in the patient’s degree of motivation or drive?

Has the patient developed a set of purposeless repetitive behaviors?

Can the patient plan and organize daily activities appropriately, or has he or she begun to struggle to keep work, home, or social life running smoothly?

Is the patient making sound judgments, or have there been “out of character” decisions recently?

Appearance and Behavior

There is much to be gained by careful observation of the patient’s appearance, especially if the interviewer has obtained a good sense of the patient’s premorbid state. The patient’s personal grooming, dress, and general state of health provide important information about functional abilities. Even the state of the patient’s hands may reveal important information. The dry, chaffed hands of a repetitive washer, the nicotine-stained fingers of a patient with schizophrenia, and the tremor of a patient with alcohol dependence are some examples. Patients with chronic schizophrenia may be disheveled and dress unusually, with many layers of clothes or with seemingly little regard for their appearance. They may look around the room in a suspicious manner and on occasion may look for monitoring devices. Depressed patients may sit stooped, with slowing of their movements, or may be restless and agitated, rubbing and wringing their hands. Patients with a pseudodementia may find the interview too difficult and resort to frequent “I don’t know” answers. Anxious patients are visibly anxious, sweaty, and restless. Patients with a dysexecutive syndrome may make inappropriate sexual suggestions or be impulsive. The presence of abnormal movements or postures during the interview may be more informative than when the patient is being examined formally. The patient’s interactions with the examiner, administrative staff, or nursing staff may provide invaluable information.

Speech

In addition to the language disturbances just described, the examiner should note the rate and quantity of speech. Often the reaction of the examiner to the patient’s speech provides diagnostic clues. The slowed, labored speech of the patient with depression may make the interview long and tedious, whereas the rapid, pressured speech of the manic patient may leave the examiner feeling frustrated and exhausted. The disordered speech of the patient with schizophrenia leaves an interviewer perplexed.

Mood

Mood is the sustained level of emotional tone, whereas affect refers to the patient’s emotional behavior. The emotional response of the examiner to the patient provides a further indicator of the patient’s emotional state. Patients with disorders of mood such as major depressive disorder often show impairments in attention and psychomotor speed.^21,22 Bipolar disorder is associated with impairments in attention, verbal memory, and executive function. High rates of comorbid mood disturbance are associated with Parkinson’s disease,²³ Huntington’s disease,²⁴ and multiple sclerosis.²⁵ Late-onset depression is being increasingly seen as a prodrome to the dementias.¹⁴

Inquiries about a patient’s mood state may include the following:

“How have you been feeling recently?”

“Do you have periods of time when you are always down?”

In patients with speech disorders, responding to such questioning may not be possible, and close informants can be asked directly, “Does he/she seem unhappier to you than usual?” Informants are able to comment on the reactivity of mood, inasmuch as depressed patients are often unable to “brighten up.” Patients who are depressed may describe themselves as feeling sad, unhappy, hopeless, useless, blue, or “flat.” This mood state is often accompanied by disturbances in sleep, appetite, concentration, and motivation. The depressed patient conveys sadness and misery or presents as anxious and irritable. Commonly used tools for rating the severity of depressive symptoms include the patient-rated Beck Depression Inventory²⁶ and the clinician-rated Hamilton Depression Rating Scale.²⁷ Patients with elevated mood states display euphoria, elation, and irritability in association with overactivity, accelerated thoughts, disinhibited behavior, reduced sleep, and grandiose ideas. Examiners who find themselves regularly suppressing a smile or giggle in interviews with patients should always ask themselves whether the patient’s mood is elevated. Reduced intensity and narrowing of affective responses is termed blunting of affect and is a key feature of schizophrenia.

Anxiety

Anxiety, a normal and adaptive component of human psychological function that allows for the identification of danger or threat, may become inappropriate and/or excessive. Anxiety disorders include panic disorder, characterized by panic attacks (discrete, relatively brief periods of intense anxiety accompanied by somatic symptoms of sympathetic drive), agoraphobia (recurrent fear of inability to escape from situations such as being in a crowd or an enclosed area), social anxiety (fear of social situations), specific phobia (of a discrete object, such as heights or water), and generalized anxiety, which leads to diffuse anxiety on most days.²⁸ Pathological anxiety states have been associated with stroke,²⁹ Huntington’s³⁰ and Parkinson’s diseases,³¹ temporal lobe epilepsy,³² and thyrotoxicosis.³³ A history of anxiety can be sought through inquiries about increasing or frequent worrying, its source, and the presence of concomitant physiological signs such as sweating, tachycardia, shortness of breath, and tremor and whether the degree of worry seems excessive to the patient or caretaker.

An anxiety disorder with a strong relationship to neurological disorders is obsessive-compulsive disorder, which is associated with intrusive recurrent thoughts (obsessions) and repetitive behaviors or mental acts (compulsions such as counting, checking, or cleaning). Obsessive-compulsive disorder has been strongly associated with Gilles de la Tourette syndrome³⁴ and with the pediatric neuropsychiatric disorder pediatric autoimmune neuropsychiatric disorder associated with group A streptococci (PANDAS).³⁵ Symptoms of obsessive-compulsive disorder can be ascertained by questions about compulsive behaviors, such as “Do you find yourself checking/cleaning things more than once or more often than you need to?”, and obsessions, such as “Do you have recurrent, intrusive thoughts/ideas/images/impulses?”

Severe anxiety states can lead to depersonalization and derealization. These conditions can be difficult for patients to describe, but descriptions can be elicited by asking the following questions:

“Have you ever had the sense that the world around you is different or changed?” (derealization)

“Have you ever felt detached from the world around you or as if you are an observer of yourself?” (depersonalization)

Both these states may be described by patients in the prodrome of complex partial seizures, although are most commonly seen in patients with anxiety or panic disorders. Patients with panic disorder describe symptoms lasting many minutes with a buildup of anxiety symptoms such as a sense of fear, palpitations, hyperventilation, and perioral numbness. The symptoms associated with complex partial seizures are usually stereotyped and much briefer than those seen in panic disorder.

Thought Content and Form

In a number of neurological disorders, patients may develop abnormalities in their beliefs about themselves or the environment around them. Thought content can be seen as a spectrum from normal, reality-based thinking to delusions, which are fixed false ideas out of keeping with the patient’s cultural background or education.²⁸ Delusions are categorized by the nature of their content, such as persecutory, grandiose, somatic, and erotomanic delusions or delusions of jealousy or reference. Delusions are classically associated with schizophrenia but are seen in patients with Huntington’s disease, temporal lobe epilepsy, leukodystrophies, systemic lupus erythematosus, and most forms of dementia.³⁶ Persecutory delusions are commonly seen in delirium and substance intoxication. Organic delusions are particularly associated with diseases affecting the limbic system.³⁷ In schizophrenia, delusions tend to be very well systematized (generally static and supported by an extensive belief system) and often have a bizarre nature, whereas in neurological disorders they are often poorly systematized and are predominantly persecutory.³⁸

Informants may provide the most valid and reliable history about delusional ideas, although they may be unaware of them if the patient has not voiced his or her beliefs. It is useful to directly but gently inquire about delusional ideas, using questions such as “Sometimes people feel that they are being watched, that others are planning to hurt them, or that they have special abilities that other people don’t. Have you ever felt like that?”

Mood or anxiety disorders are associated with altered thought content. Depression is associated with thoughts such as “Everything seems black,” “I will not get better,” or “Life is not worth living” or with suicidal ideas. Mania is associated with thoughts such as “I am immortal,” whereas anxious patients may express thoughts such as “Something terrible is going to happen.” Suicidal ideation or other thoughts involving harm should always be carefully asked about and documented, including ideas, plans, and intent. When patients clearly express all three, the patient can be seen to be at grave risk of acting on these ideas and usually requires hospitalization.

Thought form refers to the structure of thought and is necessarily conveyed through speech. The form of thought may be fragmented and interspersed with pauses in the delirious patient. Thoughts that progressively veer away from the question (tangentiality) or that do not follow logically from each other (loosening of associations) are almost pathognomonic of schizophrenia. The manic patient with flight of ideas displays a flow of thought that is rapid and determined by factors other than the logical flow of ideas, such as the sounds of words (clanging).

Perception

Perceptual experience occurs on a continuum, with “true” perception of stimuli at one end and frank hallucinations at the other.³⁹ Hallucinations are defined as percept-like experiences in the absence of an external stimulus that are spontaneous and unwilled and cannot be readily controlled.⁴⁰ Illusions, which are distortions or elaborations of a normal stimulus, also belong to this continuum. Hallucinations can be well formed and complex or poorly formed and simple,⁴¹ and they are categorized according to sensory modality. Complex and elaborate auditory hallucinations are the hallmark of schizophrenia but can occur in severe affective psychotic states. Poorly formed, fragmented auditory hallucinations may be present in organic states such as delirium. Special note should be made of complex visual hallucinations, which are often a feature of organic states. Examples include the Charles Bonnet syndrome and peduncular hallucinosis, where lesions to the visual pathways and to their terminations or ascending inhibitory afferent pathways, respectively, can result in strikingly vivid formed scenes, complex patterns, or groups of miniature figures or animals.⁴² Olfactory, gustatory, and tactile hallucinations are not commonly experienced in psychiatric illness and should alert the clinician to the possibility of neurological conditions such as complex partial seizures or neoplasia. For patients who are reluctant or unable to discuss their experiences, questioning caretakers about behavior that might represent a reaction to perceptual disturbance, such as responding to voices or gaze movements in response to visual phenomena, may prove useful.

Vegetative Function

Vegetative functions such as sleep, appetite, and sexual drive are often disturbed in patients with neurobehavioral disturbances, particularly disturbances of mood.⁴³ Patients may complain of appetite disturbance with weight loss or gain; sleep disturbance with insomnia in initial, middle, or terminal sleep phases (the last known as early morning wakening, a characteristic of severe depression); altered libido; disturbances in energy and motivation; and impaired capacity to enjoy usual pursuits.

Insight and Judgment

A patient’s lack of insight into illness may reduce the validity of a history, such as the patient’s self-report of memory complaints⁴⁴ or of adherence to prescribed treatments.⁴⁵ Insight has been traditionally viewed in both psychological and cognitive frames. In the psychological frame, insight relates to acceptance of illness and the need for its treatment. Insight is impeded by denial of illness, which occurs to varying degrees and reflects psychological coping mechanisms that allow the patient to deal with the fear, hopelessness, or shame associated with sickness and its treatment.⁴⁶ Cognitive models focus on the neurocognitive capacity of an individual to internalize, retain, and cognitively process the awareness of symptoms, attribute these to an illness, and appreciate the likely effects of accepting or refusing treatment.⁴⁷ Cognitive models of insight were devised from the strong association of disorders in which disrupted frontal-executive function is the cognitive hallmark, such as frontotemporal dementia and schizophrenia, with poor insight.^45,48 An apparent change in insight is likely to reflect an organic process, inasmuch as the psychological mechanisms that relate to insight tend to be personality based and thus relatively stable.⁴⁹

The concept of insight overlaps with the neurological symptom of anosognosia, a lack of awareness of neurological deficit, first described by Babinski⁵⁰ and most commonly seen in right hemisphere stroke. Although it most commonly characterizes a lack of awareness of hemiparesis, anosognosia can also occur for amnesia, apraxia, aphasia, cortical blindness, and prosopagnosia.⁵¹ The observation that most lesions associated with anosognosia involve the parietal lobes or related connections reinforces the role of the parietal lobe in awareness of illness and, in particular, the role of the right inferior parietal cortex in attention.⁵²

A patient’s insight can be inquired about with open-ended questions such as “Why do you think you have come to see me today?” and “In what way does this problem affect you?”

More direct, closed-ended questioning such as “What would happen if you stopped your tablets?” is appropriate afterward.

Apathy

Apathy is best defined as a state of reduced or absent motivation.⁵⁴ In practice, apathy manifests as a reduction in the initiation of goal-directed behavior. Apathy is most common in disorders that disrupt the frontal-subcortical circuit, considered to be the substrate for motivated behavior. This circuit includes the anterior cingulate cortex, nucleus accumbens, globus pallidus, and thalamus.⁵⁵ Disruption to these circuits with consequent apathy is seen in frontal-subcortical dementias such as Parkinson’s disease, Huntington’s disease,^56,57 and frontotemporal dementia; traumatic brain injury⁵⁸; schizophrenia⁵⁹; and vascular insult.⁶⁰ Apathy in many of these syndromes may respond to stimulant medication,⁶¹ and in schizophrenia, atypical antipsychotic agents may reduce apathy through increased dopamine release in the frontal cortex.⁶²

On history, the differentiation of apathy from depression can be difficult, although patients with pure apathy often blandly deny feeling depressed and do not transmit a depressed affect. The other cardinal features of depression, such as neurovegetative disturbance, are often absent. Family and caretakers may become angry or resentful at a patient whose worsening apathy is perceived as a voluntary withdrawal. The distinction between apathy and depression is important, so that an apathetic patient with frontotemporal dementia does not receive an incorrect diagnosis of depression, which leads to delays in appropriate management, or, conversely, so that patient with a reversible clinical depression does not remain untreated.⁶³

Disinhibition

Inhibition is the capacity to cognitively “cancel” a thought, response, or activity that is considered unintended, unwanted, or inappropriate. Social disinhibition is associated with insults to the nondominant inferior frontal cortex⁶⁴ and linked subcortical structures. Lesions to these regions result in release of motor, affective, instinctive, or cognitive behaviors such as hyperactivity, elevated mood, hyperorality and hypersexuality, and accelerated or grandiose thinking.⁶⁵ Disorders that produce disinhibition include focal vascular, neoplastic or traumatic lesions,⁶⁶ and frontotemporal dementia.⁶⁷ Cognitive disinhibition of automatic responses to stimuli is associated with lesions of the anterior cingulate cortex and impaired performance on tasks such as the Stroop test. (See also Chapter 7.)

Many patients may not be able to relate disinhibited behavior but can be questioned about behaviors that they “wouldn’t usually do,” such as excessive spending, substance use, social or sexual inappropriateness, or risk-taking behavior. Understandably, caretakers are usually able to relate a history of such behaviors, particularly if it represents a change from previous behavior.

Stereotypies

Stereotypies are repetitive, rhythmical, and invariant motor behaviors, without an apparent purpose or function, that can vary from simple motor behaviors such as rocking or hand waving to extraordinarily complex acts and rituals.⁶⁸ They are one of the defining features of autism and are common in patients with mental retardation.⁶⁹ Stereotypies are seen in adults with lesions or disorders affecting the frontostriatal circuit running between the dorsolateral frontal cortex and the head of the caudate nucleus.⁷⁰ Frontotemporal dementias commonly manifest with stereotypic behaviors resulting from degeneration of the dorsolateral prefrontal cortex.⁷¹ Stimulant medications can produce complex stereotypies through a dopaminergic effect on the basal ganglia.⁷² Other repetitive motor behaviors such as compulsive behaviors and tics are seen in patients with Gilles de la Tourette syndrome and obsessive-compulsive disorder, both of which are considered to be associated with basal ganglia pathology.^72,73 Of importance is that stereotypies, compulsions, complex tics, mannerisms (unusual or pathological styles of performing goal-directed activities, such as a bizarre gait and unusual ways of greeting people), and habits can often be difficult to distinguish purely on the basis of subjective observation. The context and history of the motor phenomena provide important diagnostic information.

Utilization Behavior

Utilization behavior refers to the phenomenon in which patients grasp and purposively use objects within their reach, even though this action may be inappropriate or out of context.^74,75 It reflects an inability to inhibit an automatic action cued by an environmental stimulus. It has been described in patients with lesions affecting the prefrontal/subcortical circuits.^75,76 Examples given by Lhermitte⁷⁵ included “pouring” from an empty jug into a glass, using a knife and fork on a plate without food, and lighting multiple cigarettes for the examine while the first remains unsmoked. An awareness of utilization behavior is important because it may be misinterpreted as odd, eccentric, or even antisocial behavior by the inexperienced examiner.

Echolalia and Echopraxia

Echo phenomena are the unsolicited and stereotyped repetition of another person’s speech (echolalia) or actions (echopraxia). These phenomena are commonly observed in patients with schizophrenia, especially during acute illness or in catatonic states. They have been well described in patients with neurodevelopmental disorders, including Gilles de la Tourette syndrome and autism,^77,78 and with various complex startle syndromes such as latah.⁷⁹ Echolalia has been described in patients with dysphasia and left hemispheric lesions.⁸⁰

Catatonia

Catatonia is a disorder associated with a number of behavioral, motor, and cognitive phenomena. Catatonic patients may be mute or akinetic; exhibit stereotypic and manneristic movements; adopt unusual postures; or exhibit negativism, waxy flexibility, mitmachen (automatic motion obedience), and gegenhalten (an increase in muscle tone in response to passive movement). Echopraxia, echolalia, and palilalia (perseverative repetition of a syllable or word) may also be present. Catatonia may be associated with psychotic illnesses such as schizophrenia or bipolar disorder, or it may be secondary to metabolic encephalopathies or primary neurological conditions, including post-encephalitic states, brain tumors, and seizure disorders. The distinction between primary psychiatric and secondary catatonias is one extreme example of the need to make a diagnosis regarding the cause of the patient’s mental state on the basis of the informant history, background history, and the physical examination alone.

Medical History

A history of traumatic brain injury, epilepsy, stroke, meningitis, encephalitis, or cerebral hemorrhage points toward the likelihood of neurocognitive or neurobehavioral disturbance. Systemic diseases with CNS involvement, such as autoimmune disorders, syphilis, and malignancy, may be revealed through the medical history. A history of infection with or risk factors for human immunodeficiency virus (HIV) should always be inquired about because of the wide-ranging effects of HIV-related illness on cognition, mood, and behavior. Smoking, diabetes, hypertension, and hypercholesterolemia increase the risk of strokes and may provide clues to the presence of vascular CNS disease.

The effects of therapeutic drugs on the CNS must always be considered. Dopaminergic agents used in the treatment of Parkinson’s disease may cause psychosis,⁸¹ and anticholinergic agents impair cognition.⁸² Treatments used for systemic disorders may produce neurobehavioral states, as is seen in the depression associated with β-interferon used for viral hepatitis⁸³ and the mania secondary to corticosteroid use for autoimmune disorders.⁸⁴ Polypharmacy, particularly in the elderly, increases the likelihood of medication neurotoxicity.⁸⁵ The possibility of drug withdrawal states warrants specific inquiry about the use of benzodiazepines, sedatives, hypnotics, and alcohol.

Psychiatric History

A psychiatric history allows the clinician to differentiate between a relapse of an established disorder and new-onset disease. The neurocognitive deficits of chronic schizophrenia may manifest as a dementing illness⁸⁶; “hypofrontal” disinhibition and poor judgment may be the presenting symptoms of mania⁸⁷; and patients with depression may present with a “pseudodementia.”⁸⁸

Family History

Because of the strong genetic basis for many neurobehavioral and neurocognitive disorders, a detailed family history is essential. This should include age; cause of death; history of neurological, neurobehavioral, or systemic disease; and a history of consanguinity. In some jurisdictions, cases of disorders such as Creutzfeldt-Jakob disease must be reported to the appropriate authority, such as the Centers for Disease Control and Prevention, and it may be possible to consult disease registers to confirm a family history, inasmuch as about 10% of cases of Creutzfeldt-Jakob disease are dominantly inherited.

Substance Use History

A thorough longitudinal alcohol history is essential for the verification of Korsakoff’s amnesia, alcoholic dementia, delirium tremens, and alcoholic hallucinosis, A smoking history should be obtained, including total exposure and past or current related illnesses. Stimulants such as amphetamines may produce neurobehavioral symptoms such as delusions and hallucinations,⁸⁹ chronic marijuana usage may lead to psychosis and cognitive impairment,⁹⁰ and inhalant solvent abuse has been associated with acute and chronic cognitive impairment, depression, and psychosis.⁹¹

Neuropsychiatric Inventory

The NPI⁹² is a semistructured clinician interview of caretakers in which the severity and frequency of disturbance in 12 symptom domains is rated (Table 1-2). The NPI shows good interrater and test-retest reliability.⁹² It has been modified and validated for use in nursing homes (NPI-NH)⁹³ and in various non-English versions.^94–97 Scoring in subscales of the NPI has been shown to correlate strongly with those in other well-validated symptomatic scales, such as the Behavioral Pathologic Rating Scale for Alzheimer’s Disease (BEHAVE-AD) and Hamilton Rating Scale for Depression.⁹⁸

TABLE 1-2 Symptom Domains Rated by the Neuropsychiatric Inventory

* Additional domains in the Neuropsychiatric Inventory for nursing homes.

The performance characteristics of the NPI have been established in a range of neurological conditions, including Alzheimer’s disease,⁹⁹ Parkinson’s disease,¹⁰⁰ frontotemporal dementia,¹⁰¹ progressive supranuclear palsy,¹⁰² corticobasal degeneration,¹⁰³ mild cognitive impairment,¹⁰⁴ Tourette disorder,¹⁰⁵ subcortical vascular ischemia,¹⁰⁶ multiple sclerosis,¹⁰⁷ and Huntington’s disease.³⁰ The NPI has a key role alongside cognitive scales in monitoring the noncognitive improvements with cholinesterase inhibitor treatment of various dementias, and it has been shown to reliably detect improvement in individuals treated with donepezil,¹⁰⁸ galantamine,¹⁰⁹ and rivastigmine.¹¹⁰

Neurobehavioral Rating Scale

The NRS is a 27-item, multidimensional instrument designed to measure neurobehavioral disturbance after traumatic brain injury.¹¹¹ Based on the Brief Psychiatric Rating Scale,¹¹² the NRS is a brief structured patient interview that takes 15 to 20 minutes to complete. It includes ratings of neurobehavioral symptoms, basic tests of cognition, and questions about the patient’s current level of function. The NRS has demonstrable utility in assessing a number of different organic neurobehavioral states, including traumatic brain injury,^113–116 dementia,^117,118 Parkinson’s disease,¹¹⁹ HIV-related dementia,¹²⁰ and the post-endarterectomy state.¹²¹ As with the NPI, translations of the NRS into other languages have been made and are of proven validity.¹²¹

Principles of Cognitive Assessment

When to undertake neurocognitive examination

A neurocognitive examination should be undertaken whenever the reported complaint is a cognitive one, in clinical circumstances in which cognitive impairment occurs frequently (postsurgically, in cerebrovascular disease, in neoplasia, or in trauma), or when there is an unexplained history of personality, functional, or behavioral change. In many countries, standardized cognitive assessment is mandatory before the prescription of cholinesterase inhibitors for dementia.

General observation

Much can be gained from general observation of both patient and informant and from the physical examination. A patient’s grooming and state of hygiene can be indicators of impoverished motivation and drive or of hemineglect. Alterations in gross motor activity, such as agitation or retardation, and the presence focal movements such as tremor, tics, or choreiform movements should be noted. The state of a patient’s sensorium can be ascertained by his or her capacity to sustain attention during the interview process and his or her capacity to filter out extraneous stimuli. Memory impairments may become obvious during clinical interview if a patient is unable to provide a history of recent events or the illness, as may a history that is poorly elaborated or impoverished. Impairments in insight into illness may be apparent at the outset if a patient denies any abnormality, if the history is discrepant with that obtained from an informant, or if a patient is unable to make the link between subjective complaints (such as impaired memory) and functional decline (such as driving difficulties or home safety concerns).

Setting

The examiner should ensure that enough time is allowed for the examination; that the environment is quiet, well-lit, and nondistracting; and that the patient’s usual sensory aids such as glasses or hearing aids are available. At the outset of examination, the role of the caregiver in this aspect of the assessment should be clearly defined. Many patients manage cognitive difficulties through reference to or reliance on a spouse or caretaker. It is important that this is not replicated in the assessment situation, in which a caretaker might subtly assist the patient during neurocognitive testing. When necessary, the participation of appropriately trained interpreters, who do not “help” the patient and who are skilled in the translation of linguistically difficult or culturally specific items, is invaluable. Finally, due consideration should be given to the patient’s level of fatigue and cooperation. Patients who have completed a long clinical history and physical examination may not be able to perform optimally during neurocognitive assessment, and it may be necessary to schedule a second session at which the assessment can be completed.

Quantitative versus qualitative data

When quantitative screening or assessment instruments are used to gauge cognition in patients, it is important for the clinician to look beyond the quantitative result in making a diagnosis. For example, a score of 22 of 30 on the MMSE is below most accepted cutoffs for dementia, but it may not point definitively to organic cognitive impairment. Such a score may be seen, for example, in individuals of limited education, in patients sedated by medication, or in patients with psychiatric illness such as major depression or schizophrenia. The quality of a patient’s performance is as important as the numeric measure in many or most quantitative tests; examples include perseveration displayed on a serial subtraction task or in a copying or clock-drawing task (Fig. 1-1). Further details of the quantitative aspects of neuropsychological testing may be found in Chapter 2

Figure 1-1 Perseveration in a copying task and in a clock-drawing task.

Examination of Attention and Orientation

Testing of orientation to time is more sensitive to cerebral dysfunction than testing of orientation to place, and impaired orientation to person should raise the possibility of a psychogenic fugue state. Successful completion of tests of orientation requires intact memory and expressive language; that is, these are not “pure” tests of attention. When time orientation is tested, orientation to the approximate time of day (within 1 hour), should be assessed as well as that to the day of the week, month, and year, and is perhaps the most reliable and sensitive. Disorientation as to the exact date has a very high base rate in the normal population and is rarely clinically useful. Marked disorientation to time is most common in patients with delirium or Korsakoff’s amnesia. Orientation is often preserved in early dementia.

Attention has traditionally been tested by serial subtraction tasks and reverse spelling of words, such the serial sevens and “WORLD” backwards tasks in the MMSE. Such tasks are dependent on working memory, as well as on calculation and spelling, respectively, both of which are strongly related to educational background and both of which may be disrupted by focal lesions that do not otherwise impair attention.¹²³ Reciting an overlearned sequence such as days of the week or months of the year in reverse order requires sustained attention and intact working memory; this test is very sensitive to disturbance of attentional processes and is generally understood across cultures and languages. Repeating a spoken sequence of digits, starting with two digits and increasing the length of the sequence with each correct attempt, is also a sensitive marker of attention, particularly when the patient needs to repeat the sequence in reverse, which is more difficult and places a greater load on working memory. Most subjects correctly complete 7 ± 2 digits forward and 5 ± 1 in reverse. Digit span testing depends on intact working memory, the frontal lobe–mediated brief store of visual or auditory information in current consciousness (e.g., remembering a telephone number before writing it down). Continuous performance tasks, which require the patient to respond when a particular stimulus is presented (e.g., the letter “A” in a list of random letters read by the examiner⁹) are minimally dependent on working memory but are good measures of sustained, directed attention. Finally, it is important for the clinician to be aware that attentional impairment may impair performance in other parts of the cognitive examination. If attention is markedly impaired, poor results on testing in other domains may not necessarily indicate that function in those domains is also impaired (Table 1-3).

TABLE 1-3 Tests of Attentional Function

Examination of Language

As with attentional disturbance, impaired language can affect many other aspects of the neurocognitive examination and hence should be tested early. A significant subjective understanding of the patient’s capacity for language can be gained during the clinical interview with regard to the degree of spontaneous speech, articulation, capacity for word-finding, and comprehension (Table 1-4).

TABLE 1-4 Tests of Language Function

Comprehension of language is often aided by nonverbal communication, and patients with language disturbance may be able to respond appropriately to verbal communication by relying on nonverbal cues. Comprehension should be tested in a variety of tasks of different degrees of difficulty to detect subtle impairment and, ideally, should be tested in both written and verbal form. Where expressive speech is not possible, motor rather than verbal responses indicating comprehension should be sought. At its most simple, it can be tested by yes/no responses to simple/rhetorical questions (“Is today Friday?”) and also to more difficult ones (e.g., “If the lion and the tiger have a fight, and the lion is eaten by the tiger, is the tiger still alive?”) Comprehension is also frequently tested with multistage commands, such as the paper-folding item in the MMSE, but these too are dependent on working memory. Reading comprehension can be tested by asking the patient to read through a short paragraph from a newspaper or magazine article. Repetition should similarly be tested with a graded series of tasks of increasing linguistic complexity and may be impaired in isolation in the presence of intact comprehension or expression. Initially starting with monosyllabic or oligosyllabic words, the examiner should progress to simple phrases and to more complex sentences, such as the commonly used “No ifs, ands, or buts” phrase and more difficult-to-articulate phrases, such as “The orchestra played, and the audience applauded.”

Naming to confrontation is commonly impaired in aphasias, and such impairment is commonly associated with word-finding difficulties in spontaneous speech. Anomia, the inability to name objects, can be objectively tested with a confrontation naming task. When this test is conducted at the bedside, objects from various categories should be used (colors, body parts, room objects, parts of objects), and it is important to use uncommon items (“knuckle” on the hand, “winder” of a watch), as well as common items such as pens, shoes, and watches, because many aphasic patients reveal their anomia only when confronted with uncommon items. As with poor performances in other domains, naming difficulties may also arise from other causes, such as visual agnosia.

Reading is the language task in which performance is most determined by educational status, and poor literacy is not uncommon in many patient populations. The capacities to read aloud and to understand written language are potentially dissociable and should be tested separately. Patients should be asked to read simple and then complex words, particularly comparing the pronunciation of orthographically regular (sounded as spelled) words such as “shed” to irregular words such as “rough,” as well as phrases such as “Close your eyes.” Writing should be tested to detect agraphia, which frequently accompanies aphasia. Agraphia is diagnosed when basic language errors, gross spelling errors, or paragraphias (word or syllable substitutions) are present. The patient should be asked to write sentences both spontaneously and in response to dictation, with the latter ideally containing a number of orthographically irregular words and/or homonyms (“The boy’s aunt made a large pie out of steak and dough”). Further details of language assessment can be found in Chapter 3.

Examination of Visuoperceptual/Visuoconstructional Function and Calculation

Visual and constructional impairments are often present with parieto-occipital lesions, particularly of the nondominant hemisphere, which, in combination with lesions of prefrontal regions, is important for spatially directed attention.¹²⁴ When ventral occipitotemporal regions are affected, visual recognition is impaired, particularly for objects, written words (pure alexia), colors, or faces (prosopagnosia). Dorsal lesions result in impairment of visuospatial organization. A detailed exposition of disorders of visual perception may be found in Chapter 5. When a patient is unable to maintain attention to one side of his or her spatial field or body soma, visual and somatosensory neglect, respectively, are said to occur and are typically seen with nondominant parietal lesions. Lesions in the dominant parietal region may result in Gerstmann’s syndrome, which, in addition to agraphia, manifests with calculation dysfunction (acalculia), right/left disorientation, and naming inability for fingers (finger agnosia). A disorder of skilled movement, apraxia, occurs when lesions in a network that includes the inferior dominant parietal region result in the loss of the ability to perform the “formulas for movement” stored in this region of the brain (ideomotor apraxia) or the capacity to perform a series of actions such as putting a letter in an envelope, sealing it, and stamping it in the correct sequence (ideational apraxia).

Visuospatial organization is commonly tested by tasks of figure drawing or copying, such as figure copying or clock drawing, although the latter taps into many cognitive functions and can be considered as a cognitive screening test in its own right.¹²⁵ A gradient from simple to complex figures should be used, and patients can also be asked to spontaneously draw figures such as a house or a tree. Many different ways to conduct and score clock drawing tasks have been published, although most require subjects to correctly place all numbers on the clock and appropriately place hands demonstrating a time in response to command. Most constructional tests are sensitive for visual neglect, which can also be tested by line bisection tasks. Orobuccal and limb praxis should be tested separately because they are controlled by different neural pathways. Dominant and nondominant sides should be tested separately. Patients should be asked to demonstrate a movement such as using a comb and to imitate the examiner’s movements. The latter can be done in a systematized manner by using the interlocking finger test.¹²⁶

Calculation should be specifically tested by means of simple arithmetic in addition to functional real-life examples but is often tapped by the serial sevens test (Table 1-5).¹²³

TABLE 1-5 Tests of Visuoconstructional Function, Prascis, and Calculation

Examination of Memory

“Memory disturbance” is most commonly used to refer to a disorder of episodic, declarative memory (memory for things that can be stated). This manifests as difficulty in recalling personally experienced material from the past and/or learning new information, and it is often found in dementing disorders such as Alzheimer’s disease and in amnestic disorders such as Korsakoff’s syndrome. Declarative memory has traditionally been divided into immediate, recent, and remote memory. Immediate memory is now more commonly described as working memory and refers to the very brief storage of the auditory and visual contents of current consciousness in the dominant perisylvian language areas of the cortex and the nondominant parietal cortex, respectively, and under frontal executive control. Recent memory is the term traditionally used by physicians to describe the capacity for new learning of verbal and visual material. The consolidation of recent memories is a function of the hippocampus, related structures in the medial temporal zones, and hippocampal outflow through the fornices to the mammillary bodies and thalamus. Remote memory is a time-based distinction, but the term may be used to imply that the relevant memories are consolidated and no longer hippocampally dependent. Remote memory is made up of autobiographical, episodic memory (memory for events) and semantic memory (memory for knowledge and words, dependent on anterior temporal neocortex). The nosology of the various memory systems and their disorders is covered in detail in Chapter 4.

Working memory is usually tested by items such as digit span or by the immediate recall of a word list. Recent memory is generally tested with delayed recall of a word list, name and address, or a short story. Patients with a primary deficit in registration or encoding of memory (e.g., as in Alzheimer’s disease) demonstrate rapid forgetting and limited spontaneous recall and do not benefit from the provision of clues. Patients with lesions affecting dorsal prefrontal circuits have poor or inefficient retrieval of normally registered memory and show limited spontaneous recall but may benefit from cueing.¹²⁷ Nonverbal memory should be tested through the reproduction of a visual figure after a delay. Ideally, these figures are constructions that do not lend themselves to a verbal description, as then patients can use intact verbal memory as a “workaround.” Testing for nonverbal recall is not included in the MMSE, but it is featured in other brief tools such as the Neuropsychiatry Unit Cognitive Screening Instrument (NUCOG)¹²⁸ and is illustrated in Figure 1-2.

Figure 1-2 Testing for nonverbal recall.

Remote memory is tested by the patient’s recall of personal history and his or her general fund of knowledge. The latter may be difficult to test in a standardized manner, inasmuch as commonly used questions about political leaders or historical events are strongly education- and culture-dependent (Table 1-6).

TABLE 1-6 Tests of Memory Function

Examination of Executive Function

Control of executive functions is commonly ascribed to the prefrontal lobes and related subcortical structures, although this involves a deliberate simplification. Executive dysfunction may be seen in focal prefrontal lesions, frontotemporal dementias, or neurobehavioral syndromes such as schizophrenia and major depression, among other disorders. The basal ganglia and thalamus are connected to the frontal lobes through defined circuits, and lesions of these structures or circuits can manifest with executive impairment.¹²⁹ A fuller account of executive functioning and the various features of the dysexecutive syndrome can be found in Chapter 7.

Set-shifting/sequencing is the ability of the patient to shift efficiently from one cognitive set to another and to inhibit no longer appropriate responses, and its impairment manifests as perseveration.^130,131 The neural substrate for set-shifting involves the dorsolateral prefrontal cortex and its connections to basal ganglia and thalamus.¹³² The initiation of cognitive strategies is an integral but often overlooked element of the cognitive examination and is often the core deficit underlying apathy syndromes, particularly after occurrence of medial frontal lesions that affect the anterior cingulate region.⁶⁵ Abstract thinking appears to be a function of the lateral frontal zones, and impairment of abstract thinking manifests as concreteness of thinking. The orbitomedial frontal zones are involved in the processing of emotion and in judgment and planning; lesions to this region, particularly on the nondominant side, manifest as disinhibition and poor judgment.⁶⁵ The capacity to integrate abstractive and emotional functions, perhaps best illustrated in the appreciation of humor, relates to right frontal regions.¹³³

Although impairments in set shifting can be observed behaviorally, they can be directly tested with tasks of motor or written sequencing. Motor sequencing is tested with the fist-edge-palm task, which is particularly impaired in patients with dominant frontal lesions but also at the extremes of age.¹³⁴ Written sequences of alternating letters or shapes can also be used.¹³⁵ Initiation can be assessed with tests of verbal fluency by initial letter (words beginning with a particular letter) in a limited time span. Most adults score 16 to 18 ± 4 words in 1 minute. Although abstract thinking is commonly tested with proverbs, these are notoriously culturally, educationally, and age sensitive and are best replaced by questions regarding similarities (e.g., “What is the similarity between a desk and a chair?” or “What is the difference between a painting and poetry?”). Capacity to inhibit, as well as manage, interference can be tested with a “go–no-go” task where the patient is asked to provide a response to one particular examiner’s instruction, while not responding to a second, but related, instruction, such as “Tap on the table when I tap it once, but don’t tap the table when I tap it twice” (Table 1-7).

TABLE 1-7 Tests of Executive Function

Mini-Mental State Examination and the Modified Mini-Mental State Examination

The MMSE is the most widely used of a substantial number of available screening tests¹²² and is a popular clinical measure that has validated versions available in many languages. The MMSE consists of a variety of tasks, yields a summed score with a maximum of 30 points, and can generally be administered in less than 10 minutes. The tasks have been grouped into seven categories, each rationally representing a different function: orientation to time, orientation to place, registration, attention and calculation, spontaneous recall, language (naming, repetition, reading, and spontaneous writing), and visual construction. The traditional cutoff score for dementia in mixed samples is less than 24, but this requires adjustment depending on the desired sensitivity versus specificity (see Chapter 2).

The MMSE has significant content limitations. There is substantial variability in the recall of three words in healthy elderly patients, with low to moderate correlations between scores on this task and those on standard neuropsychological tests of memory.¹⁴⁸ The MMSE does not assess long-delay recall, which can result in false-negative findings in the evaluation of relatively mild memory disorder and may fail to reveal amnesia.¹⁴⁹ The “WORLD backwards” and serial sevens forms are not equivalent, and it has been recommended that they be replaced by the “months backwards” task.¹⁵⁰ A significant concern with the structure of the MMSE is the lack of specific items that test executive function and spatial recall, and the American Neuropsychiatric Association has recommended that clinicians “supplement it with specific measures of spatial functions, delayed memory, and executive abilities.”¹⁵¹ Finally, a patient’s age and level of education significantly affect MMSE scores, and this needs to be taken into account when scores are interpreted.^152,153 In response to these limitations, the more comprehensive Modified Mini-Mental State Examination has been developed and is being increasingly used in epidemiological and community-based surveys.¹⁵⁴

Neurobehavioral Cognitive Status Examination

The Neurobehavioral Cognitive Status Examination (NCSE), now known as the Cognistat, was developed for use in neurosurgical patients and involves the “screen and metric” approach in 11 cognitive domains¹⁵⁵: level of consciousness, orientation, attention, comprehension, repetition, naming, construction, memory, calculation, similarities, and judgment. The resultant profile provides a “pattern” of distribution of cognitive dysfunction across the relevant domains. The Cognistat has shown utility in a number of neurocognitive conditions, particularly dementias, but has proved less useful in populations with neurobehavioral or neuropsychiatric disorders. The Cognistat assesses some aspects of executive function but does not test sequencing, inhibition, or verbal fluency. It appears to be a reasonably sensitive tool for the detection of dementia, but at a significant cost to its specificity,¹⁵⁶ and is subject to the same effects of age and education as is the MMSE.¹⁵⁷ The screen and metric approach has been criticized for sacrificing sensitivity for expediency, resulting in false-negative results in some populations.¹⁵⁸ The Cognistat takes significantly longer to complete than the MMSE.

Addenbrooke’s Cognitive Examination

Addenbrooke’s Cognitive Examination (ACE) was developed by Mathuranath and coworkers in Cambridge¹⁵⁹ and was reported to be able to reliably differentiate frontotemporal from Alzheimer’s dementia, although this property has been questioned.¹⁶⁰ It has shown utility in parkinsonian syndromes¹⁶¹ and in differentiating early dementia from affective disorders.¹⁶² Addenbrooke’s Cognitive Examination provides a total score out of 100 and includes all items from the MMSE, which allows the clinician to generate both scores. It provides unequal scores on scales of orientation, attention/concentration, verbal fluency, language, and visuospatial function. Calculating a ratio of scores in these areas may aid in the differentiation of dementia subtypes. A revised version of Addenbrooke’s Cognitive Examination is currently being developed by the Cambridge group.

Frontal Assessment Battery

In view of the generally low inclusion rates of executive function testing in most screening tools, a further option is to use a dedicated executive battery such as the Frontal Assessment Battery, which has shown good correlation with neuropsychological measures of cognitive function and discriminant validity for patients with frontal lobe disorders.¹⁶³ The Frontal Assessment Battery may for be used to supplement the MMSE, because of its lack of executive function testing.

Case Example

Mr. Jones, a 50-year-old executive with two teenaged children, presented for neurological assessment after a recent minor head injury in a car accident, on a background of 18 months of personality and functional change. Mr. Jones’ major complaint was of feeling rundown and lethargic, which had led his local doctor to prescribe antidepressants. His wife had noted that, for the last 18 months, he had been lacking motivation, had been forgetful, and had been allocated work duties well below his level of seniority. The family history revealed that Mr. Jones’ father had recently received a diagnosis of Parkinson’s disease after a 10-year history of gradual cognitive decline. Mr. Jones had been educated to tertiary level. There was no medical, psychiatric, or substance use history. On mental state examination, he manifested psychomotor retardation with poor grooming and a relative lack of concern regarding the recent events in his life. He did not describe depressed mood or communicate a depressed affect. He was oriented and performed well on attentional and memory testing. There were no abnormalities of visuoconstruction, praxis, left/right orientation, or calculation. He performed normally on language tasks. He had difficulty with a three-step motor sequencing task, could name only five animals in 1 minute (Fig. 1-3) and gave concrete responses on a task of similarities. He scored 29 out of 30 on the MMSE. Neurological examination findings were normal except for bilateral grasp reflexes.

Figure 1-3 Verbal fluency by semantic category (animals) in 15-second epochs: impaired in a case of frontotemporal dementia.

The neurocognitive history revealed personality and functional change, decreased motivation, slowing, and blandness of affect in a man with a family history of a dementia. Bedside cognitive testing yielded a normal MMSE score, but he performed poorly on tasks of executive function. The neurological finding of bilateral grasp reflexes was considered abnormal. A provisional diagnosis of a frontotemporal dementia was made, and investigations were ordered. Magnetic resonance imaging showed bilateral frontal atrophy out of keeping with his age, together with mild enlargement of the frontal horns of the ventricles; cerebral single photon emission computed tomography revealed bilateral frontal hypoperfusion. Neuropsychological testing confirmed the executive deficits and provided a baseline of cognitive performance for future reference. Several significant issues needed to be addressed in the ensuing months, including the possibility of a genetic condition and its implications for his young family, his ability to work and drive, and the effect of an early dementia on his family.