Cognitive assessment in Behavioral Neurology

Amir Babak Ghaemmaghami, MD 
Neurologist
One of the challenges facing behaviorally orientedneurologists is that many patients' symptoms fallbeyond the scope of a physical neurological evaluation.Frequently, patients with neurodegenerative disease,particularly in the early stages, present with intactcranial nerves, reflexes, eye movements, and sensory-motor function. Accordingly, clinicians need tools to formally assess the cognitive, psychiatric and behavioral abnormalities that define many dementing disorders.
 
The mental status examination is the part of the neurological examination that assesses current mental capacity through evaluation of appearance, mood, perceptions (e.g. delusions, hallucinations) and all aspects of cognition (e.g. attention, orientation, memory). A comprehensive mental status examination evaluates 10 areas of functioning: (1) overall appearance, (2) movement and behavior (gait, coordination, eye contact and facial expressions), (3) mood (underlying emotional tone of person's answers), (4) affect (outwardly observable emotional reactions), (5) speech (volume, rate, tone, appropriateness and clarity), (6) thought content (hallucinations, delusions, obsessions, dissociative symptoms and thoughts of suicide), (7) thought process (repeated words or phrases, thought blocking, illogical connections), (8) cognition, (9) judgement (what to do about a common sense problem) and (10) insight (ability to recognize a problem and understand its nature and severity). This manuscript will describe some widely used approaches for assessing mental status, with a particular emphasis on the cognitive changes typically seen in neurodegenerative disease.
 
Several standardized mental status examinations exist that enable quantification of cognitive impairment, typically yielding a single composite score that reflects disease severity. Some examples include the Mini-Mental State Examination (MMSE), Modified Mini-Mental State Examination, Short Portable Mental Status Questionnaire, Cognitive Abilities Screening Test, Cognistat (or Neurobehavioral Cognitive Status Examination, 7 Minute Screen, and Geriatric Mental State Schedule. Perhaps the most widely used measure in behavioral neurology and dementia is the MMSE. Typically taking about 10 minutes, the MMSE evaluates orientation to time and place, registration, attention, working memory, recall, language and visuoconstruction. This 30-point scale was originally designed to facilitate differential diagnosis of hospitalized psychiatric patients, but it is now routinely used to assess cognitive abilities in a broad range of diagnoses. There was high test–retest reliability in the original standardization sample of 22 non-demented psychiatric inpatients over a 24-hour period, whether the examiner was the same both times (r¼0.89) or different (r¼0.83). Test–retest reliability over a 4-week period was nearly perfect for 23 patients with dementia (r¼0.99). Studies have demonstrated considerable incremental validity of the MMSE in comparison with routine clinical evaluation.
Additionally, significant correlations have been found with many neuropsychological measures, suggesting high convergent validity examined the distribution of MMSE scores in 18 056 adult participants. They found that cognitive performance as measured by the MMSE scores varied by both age and education level. There was an inverse relationship between age and MMSE scores and a positive relationship between years of education and MMSE scores. For example, the median MMSE score of those aged 18 to 24 was 29, while the median score for individuals 80 years old and above was 25. Furthermore, the median MMSE score for participants with at least 9 years of formal education was 29, while the median score for those with 0–4 years ofeducation was 22. These data highlight the need to consider age and education when interpreting MMSE scores. The strength of tests like the MMSE is that they provide composite scores that can be used as markers of disease severity over time.
The MMSE performance of healthy older adults is reasonably stable over time, while MMSE scores of patients with Alzheimer's disease (AD) decreases over time at an average rate of around 3 points per year. In addition, patterns of performance on individual items on the MMSE may help to distinguish patients with different dementia etiologies. For example, patients with dementia with Lewy bodies (DLB) performed worse than patients with AD on attention and construction items, whereas patients with AD performed worse on the MMSE memory items. Patients with AD tend to perform poorly on temporal orientation items and delayed recall.  
However, tests like the MMSE are not particularly sensitive indicators of early disease manifestations. Also, it is important to remember that the MMSE was designed primarily for quantifying dementia severity and not for differential diagnosis.
Therefore, in some instances, the behavioral neurologist will need to assess skills such as episodic memory, working memory, executive functions, language and visuospatial abilities in greater detail.  Then, it will provide typical neuropsychological profiles of various dementia types (AD, frontotemporal dementia [FTD], semantic dementia [SD], DLB and progressive supranuclear palsy [PSP]) in order to aid in differential diagnosis.
 
Cognitive mental status examination Memory
 
Most patients with dementia show memory problems early in the course of their disease. Memory is a general term for a mental process that allows the individual to store information for later recall. Importantly, memory is not a unitary construct, but rather an alliance of inter-related subsystems. Episodic memory refers to the system involved in remembering particular experiences or episodes, such as what you had for breakfast or where you went on vacation last summer. These memories are context dependent and are associated with a particular time, place and feelings. Episodic memory depends on a neural network that includes the temporal lobes, hippocampus and frontal lobes. The hippocampus is a structure within the temporal lobes that is crucial for consolidating information into long-term storage. Focal hippocampal injury produces impaired new learning in the context of intact immediate and remote memory. When assessing episodic memory in the clinic, examiners should use enough information to exceed immediate memory span, and to consider separately initial learning versus retention, and recall versus recognition. Some examined the utility of using three-word recall tasks (such as the task in the MMSE) for assessing recall performance. They found substantial variability within their subjects, and a significant proportion of normal subjects recalled zero or one word. They noted that caution must be used when interpreting simple recall performance as an index of memory. Supraspan list-learning tasks with delayed recall and recognition conditions (e.g. California Verbal Learning Test-II; CVLT-II] and Rey Auditory Verbal Learning Test are better suited for bedside evaluation of memory. Different neurodegenerative conditions can affect memory functioning in different ways. Patients with fronto-subcortical atrophy have problems with encoding and initial learning, but relatively intact retention. In addition, recognition memory is often within normal limits. In contrast, patients with AD may show normal immediate recall but have difficulty retaining information over delays as brief as a few minutes and tend to have poor recognition. They demonstrated the importance of examining delayed episodic memory and not just immediate memory when conducting a dementia evaluation. They found that delayed recall was best predicted by hippocampal volume, even after controlling for levels of initial acquisition.
These results suggest that impaired delayed recall may be used as an indicator of hippocampal dysfunction, while difficulty with immediate recall may reflect problems in other brain regions involved in attention and organization.
 
Executive functions
 
Executive functioning has been called the subtlest and central realm of human activity. It is particularly important to assess because it is affected in most types of dementia. Executive function is the process of bringing together and coordinating information for a purpose, such as decision making, and it includes skills such as mental flexibility and response inhibition. Lesion studies and structural and functional neuroimaging studies have implicated the prefrontal cortex as critical for performing executive function tasks. However, poor performance on executive function tasks should not always be construed as evidence for frontal pathology because many such tasks are cognitively complex, and other brain regions, including subcortical structures, play an important role in task completion. Several clinical tasks have been developed to assess different aspects of executive function, including novel verbal and non-verbal problem-solving tasks, maze tracing, tower tests, card or object sorting, and set-shifting. Common areas assessed under the rubric of executive function include working memory, mental flexibility, inhibition, fluency and abstract reasoning.
 
Working memory is a functional system that works to register, recall and mentally manipulate information within short-term memory; it is a common substrate to patients' difficulty with multitasking. Digit span tests are widely used, with the forward digit span component used to assess immediate auditory memory, and the backward span component evaluating working memory (i.e. the capacity to juggle information mentally). Research has shown that, on average, people can keep 7_2 items in their short-term memory (which is why the US Federal Government made phone numbers seven digits long). Working memory is also assessed on the MMSE when the patient carries out serial 7's or spells “WORLD” backward. Other bedside techniques include reciting the months of the year in reverse order.
 
Mental flexibility
 
The Trail Making Test is a widely administered test of attention and cognitive flexibility. In Part A of the Trails, patients connect a series of numbered circles distributed arbitrarily on a page. In Part B, the subject is asked to alternate serially between connecting numbers and letters. The scores are the time taken to complete each part. This test is particularly sensitive to the progressive cognitive decline in dementia. Elderly persons who perform poorly on Part B are likely to have problems with complex activities of daily living.
 
Inhibition
 
Response inhibition requires the patient to suppress an overlearned response or a salient environmental stimulus. Stroop interference tests are widely used to assess inhibition. In this paradigm, patients are shown a series of color names printed in different color ink (e.g. the word “RED” printed in blue ink). The patient has to inhibit the overlearned tendency to read the words and instead name the color of the ink in which the words are printed. Other tasks, such as opposite responding, require the patient to inhibit their response to a salient stimulus while providing a competing response. For example, the evaluator tells the patient, “When I tap once, you tap twice, but when I tap twice, you tap once.” Similarly, the evaluator may ask the patient to point to his/her chin while the evaluator points to his/her nose.
 
Fluency is another aspect of executive function because it requires organized search and retrieval strategies. Fluency can be assessed by having the patient generate words beginning with specified letters or belonging to semantic categories. Relative difficulty with semantic categories often suggests AD or SD, whereas relative difficulty with letter prompts (phonemic cueing) suggests frontal and/or subcortical deficits. The Controlled Oral Word Association consists of three word-naming trials using the letters F-A-S. Semantic fluency is often evaluated using the category of animals. Non-verbal fluency tasks (e.g. Design Fluency) typically present patients with boxes containing dots and asks them to generate as many novel designs as possible.
 
Abstract reasoning can be evaluated by asking patients to describe conceptual similarities or differences between word pairs (e.g. “dog–lion”), give opposites (e.g. “healthy–sick”), find analogies (e.g. “table is to leg as bicycle is to?”) or interpret proverbs (e.g. “An old ox plows a straight row”).
 
Language
 
Several aspects of language should be screened during mental status testing, including articulatory agility, repetition of high- and low-frequency word combinations (e.g. “No ifs, ands or buts”, “Methodist Episcopal”), comprehension of single words (give the subject simple commands, such as “Show me your chin,” or have the patient say the word that a picture is illustrating), comprehension of complex syntax (e.g. “Put your left hand on your right ear”), reading of regular and irregular words, and naming (point to objects in the room; name colors, letters, numbers and actions; the Boston Naming Test). Examiners should also pay close attention to several features of the patient's spontaneous and conversational speech, including intonation, prosody, typical phrase length, the presence of grammatical terms, the presence and type of paraphasia, word-finding ability and how well the patient seems to understand what is being said. Reading and writing should also be assessed. Investigators have explained some typical terminology used to describe language impairments. Agraphia is an acquired disturbance in writing. Alexia is the term used to describe a loss of reading ability in a previously literate person. Aphasia is a true language disturbance in which the patient demonstrates an impaired production and/or comprehension of spoken language. Dysprosody is an interruption of speech melody, inflection and rhythm.
 
 
 
Visuospatial abilities
 
Constructional tasks are extremely useful in detecting organic brain disease and should be included in every mental status examination. Constructional abilities require complex non-verbal cognitive functions and involve the integration of occipital, parietal and frontal lobe functions. Nevertheless, the parietal lobes are the principal cortical areas involved in visual-motor integration. Design copying (e.g. interlocking pentagons or hexagons, cube, clock, Rey–Osterrieth Complex Figure) is commonly used to examine visuoconstructional abilities at the bedside. Noticing how the patient approaches his/her copy can be an extremely useful part of the evaluation. For example, working from right to left, omitting parts of the left side, missing the overall configuration and directional confusion all raise the possibility of right-hemisphere injury, regardless of how good the final copy is. Basic perceptual skills should also be assessed in patients who fail constructional tasks. Widely used bedside measures include line bisection tasks, matching faces or designs, or even having patients describe complex pictures (assuming intact language).
 
Psychiatric symptoms
 
Personality or emotional changes are often present in patients with dementia. These changes may be a direct product of the illness itself or the patient's reaction to their experiences of loss, frustration and changes in lifestyle. It is important to distinguish personality changes that are a result of the disease from comorbid psychiatric symptoms. Common personality changes and behavioral problems include irritability, low frustration tolerance, apathy, disinhibition, emotional dulling and hoarding. Depression is likely the most common comorbid psychiatric symptom that follows a diagnosis of dementia, with pervasive anxiety following closely. It is important to assess for psychiatric disorders, such as depression, bipolar disorder, generalized anxiety disorder, anxiety disorder caused by a general medical condition, somatization disorder, conversion disorder and obsessive–compulsive disorder. Therefore, it is important to ask about domains related to a patient's emotional status, including mood, appetite, sleep, pleasurable activities they partake in, anxiety, energy level and obsessions. The Geriatric Depression Scale is useful in assessing for depression in elderly patients, and the Neuropsychiatric Inventory allows informants to rate the patient's behaviors and psychiatric symptoms.
 
Functional status
 
A diagnosis of dementia requires impairment both in cognition and in everyday functioning. Functional status refers to the capacity to carry out instrumental activities of daily living, such as food preparation, medication management, driving, housekeeping, financial management and shopping. It can be informally assessed by asking the patient if they are having difficulty carrying out these daily activities. Functional abilities can also be assessed by having caregivers’ complete questionnaires, such as the Functional Activities Questionnaire and the Clinical Dementia Rating Scale. Evaluating functional status is crucial in the diagnosis of dementia, and also in determining the practical effects of dementia on patients and their families. Components of the mental status examination that bear the strongest relationship to functional abilities are memory and executive functioning. Executive dysfunction often results in impairments in planning, organization and insight, all of which are likely to affect the ability to care for one's self. Jefferson and colleagues (2006) determined that out of the elements of executive functioning (e.g. working memory, generation, inhibition, planning and sequencing), inhibition was most strongly related to impairments in instrumental activities of daily living in patients at risk for future cognitive and functional decline. In addition to executive dysfunction, apathy (a frontally mediated behavior) was also found to be associated with impairment in instrumental activities of daily living. Sunderland and colleagues (1986) demonstrated that a story-recall test reported everyday memory problems. Wilson and colleagues (1989) found that the River-Mead Behavioral Memory Test (RBMT) was sensitive and correlated highly with lapses in everyday memory. A follow-up study by Wilson (1991) determined that the RBMT predicted whether or not a patient would be capable of living independently.
 
 
 
Suggested mental status examination
 

  1. An example of a comprehensive bedside mental status examination includes the following: MMSE, a Supraspan memory test with delayed recall and recognition (e.g. CVLT-II short form), design copy and recall, high- and low-frequency object naming (e.g. jacket, lapel, sleeve and cuff; shoe, sole, heel and tongue), naming to descriptions (e.g. “What is the name of a small lizard noted for its ability to change color”), comprehension of single words and syntax (e.g. “A lion and tiger were fighting. If the lion was killed by the tiger, which animal is dead?”), forward and backward digit span, verbal fluency (words beginning with the letter D, animals), opposite responding, similarities and proverbs, and the Geriatric Depression Scale. It is recommended that clinicians develop items they use in a standardized way. 
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