Key Points

  1. The goal of the diagnostic evaluation for cognitive impairment is to determine both the severity of impairment and the probable cause or causes. 
  2. A knowledgeable informant is crucial for a reliable evaluation and, depending on the cause, patient care. 
  3. The mental status examination should incorporate one or more validated instruments to assess cognition. 
  4. An assessment of functional status informs both the diagnostic work-up and patient care. 
  5. Environmental, psychological, and behavioral interventions are first-line for neuropsychiatric symptoms and can be beneficial for cognition and function in cognitively impaired patients.

Introduction to Cognitive Evaluation

Purpose | Approach

INTRODUCTION TO COGNITIVE ASSESSMENT

Cognitive impairment is highly prevalent in the elderly and increases with advancing age. Worldwide, studies estimate dementia to affect 1.8% of people in their 60s, 5.1% of people in their 70s, 15.1% of people in their eighties, and 35.7% of people in their nineties. A study from the Centers for Disease Control and Prevention using the 2011 Behavioral Risk Factor Surveillance Survey found that 12.7% of respondents aged 60 years and older self-reported memory loss and confusion that had worsened in the preceding year. Clinicians providing primary care to the elderly are often tasked with evaluating and managing cognitive concerns in their patient population.

APPROACH TO COGNITIVE ASSESSMENT

To diagnose and treat a patient presenting with a cognitive complaint, the clinician uses a systematic approach that identifies the presence and severity of the impairment, the cognitive domains involved, the underlying causes, and the most appropriate interventions. Although some aspects of the work-up are completed for all patients (for example, selected laboratory tests and imaging), the decision to pursue a more detailed workup is influenced by the goals of the evaluation. A brief discussion with the patient and family about the goal of the visit provides the information to customize the approach.

The decision to refer a patient to a specialist can be considered at the close of the initial assessment. Cases of early-onset, rapidly progressive, or otherwise atypical cognitive impairment (for example, prominent language or social-behavioral symptoms with little or no memory loss) should be referred to a specialist. Other factors that might influence a decision to refer include provider experience, clinic resources, patient preference, and availability of specialty centers. One particularly interesting reason to refer to an academic center is interest in participating in clinical research.

History Taking

Recognition | Signs | Symptoms | Family

History of Present Illness

A concern for cognitive change (commonly called a chief complaint of memory loss) triggers a work-up for cognitive impairment. The patient or a knowledgeable informant can voice this concern. A knowledgeable informant provides the most helpful historical information. The interview with the informant is best done privately, although this is not always practical. Privacy allows the informant to feel comfortable describing the full extent of the problem. However, there is no need to hide this conversation from the patient. In our experience, patients are agreeable to allowing the informant to speak privately with the clinician if they are told that this is a routine part of the cognitive evaluation and they will have private time as well with the clinician.

The informant interview should begin with an assessment of how long the informant has known the patient and how frequently does an interaction with the patient occurs. An open-ended question about the reason for concern often provides a great deal of information. Next, it is helpful to take a step back and learn about the patient’s cognitive achievements and background, including education, occupation, and living situation. The history covers all cognitive domains, including memory, attention, language, visuospatial processing, executive function, and social comportment, and addresses aspects of timing and tempo. Domains that are not covered when the informant answers an open-ended question can be addressed with a few "key and targeted" questions.

It is helpful to ask for examples that illustrate the patient’s symptoms. These contextual details aid the physician in assessing the severity of the problem.

After establishing the pattern of cognitive impairment, the clinician should assess the functional impact of the symptoms. The activities of daily living are the instrumental activities of daily living (IADL), such as handling finances, cooking, managing medications, and using transportation, and the basic activities of daily living (BADL), which include bathing, dressing, grooming, feeding, and toileting. An ecologically valid and holistic way to assess function is to begin by asking what a typical day is like or what the patient does to stay busy. The clinician should then ask questions to determine whether the patient’s day-to-day activities represent a change from the baseline and if so, result from cognitive problems. Questions should probe whether the patient is less efficient at performing tasks (ie, takes them longer) or makes errors and needs help.

We should discuss neuropsychiatric symptoms, both because mood disorders, especially depression, can be a primary (and treatable) cause of cognitive change and because neurodegenerative diseases can cause various neuropsychiatric symptoms. For example, dementia with Lewy bodies (DLB) often results in anxiety, systematized delusions, and formed visual hallucinations.

We should discuss sleep, both because untreated sleep disorders (for example, obstructive sleep apnea [OSA]) may affect cognitive function in some older adults and because neurodegenerative conditions are associated with sleep disturbance.   The possibility of rapid eye movement sleep behavior disorder (RBD), which is commonly seen in DLB, can be assessed by asking whether the patient’s arms and legs move during sleep as if acting out dreams.

A focused review of systems should inquire about gait dysfunction, falls, tremor, incontinence, and dysphagia. The past medical history should explain vascular risk factors and general medical, psychiatric, or neurologic diseases that could affect cognition. The social history assesses for illicit drug use, problematic alcohol use, and social stressors. Family history identifies genetic risk factors. In addition, medication reconciliation should flag drugs that contribute to cognitive decline, particularly anticholinergic drugs.

The interview with the patient should include questions about cognitive symptoms and a typical day. This history from the patient is a part of the cognitive examination because it provides information about the patient’s insight. Patients should be asked directly about their mood and hallucinations because informants do not always know this very subjective information. Validated instruments for assessment of cognitive symptoms, functional decline, and neuropsychiatric features can augment the history of present illness and provide quantitative values that are helpful for both baseline and longitudinal assessments (Table 1).

Box 1

Targeted questions to address cognitive domains. Note: these questions refer to “the patient,” but a more personal term, such as “your wife” or “your father,” is used in practice.

  • Memory

    Does the patient forget appointments or have difficulty keeping track of the day or time? Does the patient repeat questions or comments? Does the patient forget recent events or conversations?

  • Attention

    Does the patient have periods of decreased alertness? Is the patient easily distracted?

  • Language

    Does the patient have word-finding difficulties, or struggles to find familiar words? Does the patient have trouble communicating thoughts or understanding what is being said to them?

  • Visuospatial processing

    Does the patient get lost or turned around? Does the patient ever do not see something that is right in front of them?

  • Executive function

    Can the patient successfully complete tasks that require multiple steps; for example, planning a trip or throwing a dinner party? Can the patient use appliances and devices and they have used to?

  • Social comportments

    Does the patient behave appropriately in social situations? Has the patient become impulsive, careless, or unguarded?

Cognitive Examination

Clinical and neuropsychological

Examination

The mental status examination should include both a “bedside” examination and the use of one or more validated instruments to assess cognition and, if applicable, mood (Table 1). There are some scenarios in which we must interpret the results of formal cognitive tests with caution. For example, the psychometric test performance of persons with limited education, particularly less than high school, and for whom English is a second language, may underestimate their cognitive abilities. In addition, certain cognitive deficits, such as marked impairments in language or attention, can cause performance on tests that are markedly poorer than expected.

The bedside mental status examination touches on the various cognitive domains. From the start of the encounter with the patient, the clinician makes observations regarding the patient’s cognition and behavior. While taking the history, the clinician is also noting the patient’s affect, social comportment, speech, facial expressions, and insight. The versions of the bedside mental status examination are limitless, and clinicians often tailor the examination based on preference, patient factors, and the developing differential diagnosis. The various bedside tests available are best organized according to the cognitive domains they test (Box 2).

Cognitive Testing

Memory | Attention | Language | Processing


Neurological Examination

Nerves | Tone |Coordination |Gait |Sensory

Next, the clinician should perform a focused neurologic examination designed to detect findings that the chief complaint and history suggest might be present (Box 3).

Box 3: Focused neurologic examination for a patient with a cognitive complaint
Cranial nerves Assess for masked facies or reduced eye blink rate, listen for dysarthria, look for facial asymmetry, including flattening of the nasolabial fold, determine whether eye movements and visual fields are full
Motor, sensory, and reflex examination Test briefly, assessing for focal weakness, fasciculations, or hyperreflexia concerning amyotrophic lateral sclerosis, which is sometimes comorbid with frontotemporal dementia, or another asymmetry suggestive of a focal lesion (for example, stroke, tumor)
Tone Assess for cogwheel rigidity at the elbows, wrists, and neck by asking the patients to relax and allow you to move their bodies for them
Coordination and extrapyramidal function Test rapid alternating movements (for example, by having the patients alternate striking their thighs with a fist and open palm). Test for the emergence of a rest tremor by having the patients rest their hands in their laps and count backward from twenty to zero with eyes closed.
Gait and postural stability

Have patients stand without the use of their hands, observe gait (noting arm swing, posture, stride length, and turn), Assess tandem gait, use a pull test to assess for postural instability

A brief general medical examination with attention to the cardiac and pulmonary systems assesses for signs of non-neurologic problems that could affect cognition.

Referral for a formal neuropsychological evaluation should be considered when there is significant psychiatric comorbidity or when there is a mismatch between the history and the cognitive test results—for example, a patient whose cognitive test performance is normal but in whom a decline from baseline is still suspected. More in-depth testing may reveal deficits too subtle to show up on simpler office-based tests. Neuropsychologists can also help refine the differential diagnosis by identifying patterns of cognitive dysfunction.


Determining the level of impairement

The history and examination provide clinicians with the data needed to characterize the level of impairment:

  • Subjective cognitive decline

    Subjective cognitive decline (SCD) describes patients who have expressed concern for cognitive change but perform normally on cognitive testing.

  • Dementia

    Dementia describes a patient with concern for cognitive decline, objective cognitive impairment, and disability. We distinguish dementia from MCI in that the cognitive symptoms of dementia are severe enough to interfere with performing day-to-day activities.

  • Mild cognitive impairment

    Describes patients with concern for cognitive change, voiced by the patient or the informant; objective evidence of impaired cognition in one or more cognitive domains; and relative preservation of independent function, such that the patient does not meet criteria for dementia.

Investigations

Labs | Imaging

Working-up a patient with cognitive impairment

Laboratory Investigations

Clinicians should screen patients with cognitive impairment for hypothyroidism and vitamin B12 deficiency because these entities can cause cognitive decline that may improve with treatment. It is reasonable to get a complete blood count with differential and comprehensive metabolic panel to screen for other general medical problems (for example, anemia, kidney or liver failure, electrolyte derangements) that could affect cognition.   Depending on the clinical context, clinicians may consider ordering other laboratory tests, such as folate, vitamin D, heavy metal screen, erythrocyte sedimentation rate, C-reactive protein, antinuclear antibodies, Lyme serologies, human immunodeficiency virus-1/2 immunoassay, and rapid plasma-reagin. Patients in whom clinicians suspect obstructive sleep apnea should undergo a sleep-study or they should refer him to a sleep specialist.



Brain imaging 

All patients with cognitive impairment should undergo structural brain imaging. Brain imaging is not indicated in patients with subjective cognitive decline because normal age-related changes can overlap with the early atrophic changes seen in neurodegenerative disease. Thus, structural brain imaging, in the absence of objective cognitive impairment, is often clinically uninterpretable, because mild atrophy could be age-related, and a normal result does not rule out the small possibility of occult disorder.

Although both computed tomography (CT) or magnetic resonance imaging is acceptable, the preferred brain imaging modality for cognitive impairment is MRI without contrast, which has a greater diagnostic yield and avoids ionizing radiation. Computed tomography without contrast, which is less costly, is a suitable alternative when magnetic resonance imaging is contraindicated or otherwise unable to be obtained. Imaging enables the clinician both to assess for unexpected structural findings that could affect cognition (for example, a tumor, silent stroke, or subdural hematoma) and to identify features suggestive of specific underlying neurologic diagnoses. Several of the diseases that cause dementia have characteristic imaging findings (for example, hippocampal and posterior parietal atrophy in Alzheimer's disease (Table 2). However, these findings can be subtle, and the relationship between imaging findings and underlying disorder is best thought of as probabilistic, with the most compelling cases being those in which the clinical symptoms and the imaging findings align.

Neurologic Disease

Common MRI Findings

AD

Atrophy affecting the hippocampi, MTLs, and posterior parietal lobes a

DLB

Normal MRI or mild, nonspecific atrophy with relative sparing of MTLs b

Frontotemporal dementia

Atrophy of frontal and temporal lobes c

Vascular cognitive impairment

Multiple bilateral chronic lacunar strokes; white matter hyperintensities c

Normal-pressure hydrocephalus

Ventriculomegaly; disproportionately enlarged subarachnoid spaced

Abbreviation: MTLs, medial temporal lobes.

a Data from Whitwell, J. L. Progression of atrophy in Alzheimer disease and related disorders. Neurotox Res. 2010 18(3-4): 339-346.
b Data from Yousaf, T., et al. Neuroimaging in Lewy body dementia. J Neurol. 2019 266(1): 1-26.
c Data from Masdeu, J. C. Neuroimaging of Diseases Causing Dementia. Neurol Clin. 2020 38(1): 65-94.
d Data from Graff-Radford, N. R. and D. T. Jones. Normal Pressure Hydrocephalus. Continuum (Minneap Minn). 2019 25(1): 165-186.

MRI is also helpful for identifying cerebrovascular disease because many types of vascular brain injuries have identifiable imaging correlates. White matter hyperintensities, which are suggestive of chronic small vessel ischemic disease, are commonly related to typical cardiovascular risk factors (for example, hypertension, smoking), but are also commonly seen in AD.   Similarly, cerebral microbleeds (CMBs) are commonly seen in both vascular cognitive impairment and AD. Deep subcortical CMBs are usually hypertensive in origin, whereas lobar CMBs are more often associated with cerebral amyloid, and thus are suggestive of AD.

Normal-pressure hydrocephalus (NPH) can be suggested, but not definitively diagnosed, by characteristic imaging findings, including ventriculomegaly and disproportionately enlarged subarachnoid space. There has been growing recognition that mixed dementia (i.e., multiple disorders together causing the impairment) is common, particularly in the elderly.  

If the diagnosis is still unclear, additional studies or a referral to a cognitive specialist may be needed. A fluorodeoxyglucose-PET scan of the brain can distinguish between frontotemporal dementia (FTD) and AD. Amyloid PET scans are approved for the detection of amyloid by the Food and Drug Administration (FDA) in the United States, but, as of this writing, are not covered by any insurance plans. Cerebral spinal fluid from a lumbar puncture (LP) can be tested for biomarkers of specific diseases, including AD (with amyloid-beta-42 and phosphorylated tau), sporadic Creutzfeldt-Jakob disease (with real-time quaking-induced conversion), autoimmune and paraneoplastic encephalitis (with respective panels), and other inflammatory entities (with protein and white blood cell counts). A high-volume LP preceded and followed by cognitive and timed walking tests, can evaluate for NPH, in the clinical triad (gait disturbance, urinary incontinence, and dementia) and suggestive neuroimaging.

Patient Education

Diagnosis | Concerns

Providing a Diagnosis

Discussions about the diagnosis should include information about the level of impairment (MCI or dementia) and the causes. If the patient has SCD, the clinician should explain that cognitive testing was normal and provide prognostic information. Individuals with SCD are at a modestly increased risk of progression to MCI and dementia over subsequent years, compared with the general population. It is reasonable to follow the patient over time with repeated cognitive assessments to assess for the onset of objective cognitive decline. Education about cognitive aging is warranted as well.

Clinicians giving a diagnosis of MCI discuss with patients and their families the meaning of the diagnosis and its prognosis. People with MCI can progress to dementia, remain in an MCI state, or revert to normal cognition, and studies have shown that all 3 outcomes are common. Each year, 5% to 20% of patients with MCI progress to dementia.

A diagnosis of dementia merits disclosure of the disease that is causing it, or, if that cause is uncertain, an offer for a referral to a specialist. Table 3 lists abbreviated diagnostic criteria of selected commonly diagnosed neurodegenerative diseases that cause dementia. Some common dementia syndromes, such as NPH and vascular dementia, do not have a single set of widely agreed-on diagnostic criteria.


Table 3: Abbreviated diagnostic criteria for commonly diagnosed neurodegenerative dementias

Diagnosis

Abbreviated Diagnostic Criteria

AD dementia

Progressive, insidious decline with dementia-level impairment

Amnestic or non-amnestic presentation

 Amnestic (most common): impairment in learning and episodic memory

 Nonamnestic: language (particularly word finding), visuospatial, or executive function

Not better explained by another entity

• Can increase certainty with imaging or CSF biomarkers

Behavioral variant frontotemporal dementia

Progressive cognitive and/or behavioral decline

Need 3 of the following:

  • Behavioral disinhibition
  • Apathy or inertia
  • Compulsive, ritualistic, or perseverative behavior
  • Hyperorality
  • Dysexecutive presentation with relative sparing of memory and visuospatial function

• Can increase certainty with imaging biomarkers

DLBc

Progressive cognitive decline with dementia-level impairment

Core clinical features:

  • Fluctuating cognition
  • Well-formed visual hallucinations
  • RBD
  • Parkinsonism

Supportive features: sensitivity to antipsychotics, postural instability, falls, dysautonomia, delusions, anxiety, apathy, depression

Probable DLB: 2 core features or 1 core feature plus 1 indicative biomarker

• Possible DLB: 1 core feature or 1 indicative biomarker

Abbreviation: CSF, cerebrospinal fluid.

  • aData from McKhann, G. M., Knopman D.S., Chertkow H., et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 7(3): 263-269.
  • bData from Rascovsky K., Hodges J.R., Knopman D., et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011 134(Pt 9): 2456-2477.
  • cData from McKeith I. G., Boeve B.F., Dickson D.W., et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology. 2017 89(1): 88-100.


If the patient has a neurodegenerative disease, it is important to stage the disease. Diagnostic disclosure should explain that these conditions are gradually progressive, and the goal of any intervention is to slow down or stabilize the functional decline and other symptoms. Family members in particular need to understand this so they can help the patient live well with the disease and prepare for the future. Each cause of dementia has its own prognosis, but clinicians should emphasize that there is variability in rates of progression.

Cognitve Assessment Tools

Functional Activities Questionnaire

Informant questionnaire about patient’s performance of day-to-day tasks

  • Examiner administers to the informant
  • Score range: 0–30; lower scores c/w less impairment; ≥9, impaired function, and possible cognitive impairment
  • Takes 5 minutes
  • The patient must have a reliable informant
  • May help identify safety concerns and areas of need


General Practitioner Assessment of Cognition

Psychometric test of memory, language, executive function, and structured informant interview

  • Examiner administers a psychometric test to patient and interviews informant
  • Patient examination (out of 9): 0–4, cognitive impairment; 5–8, need more information (interview informant); 9, normal. Informant interview (out of 6): 0–3, cognitive impairment.
  • Takes 4–5 min
  • Eighty percent sensitivity and specificity

Geriatric Depression Scale

Thirty yes/no questions about depressive symptoms; 15-item version also available (GDS-15)

  • Examiner administers to the patient or patient self-administers
  • Score range (full version): 0–30; ≥14, increased depressive symptoms; 11–13, borderline
  • It may be less reliable for more impaired patients

Informant Questionnaire on Cognitive Decline in the Elderly 

A 26-item informant questionnaire with 5-point Likert scale; shorter 16-item version (Short IQCODE) also available

  • Informant self-administers
  • Score range 1–5 (mean Likert score); higher scores c/w more impairment
  • Seventy-five percent–87% sensitive and 65%–91% specific for dementia
  • Seventy percent–80% sensitive and 69.0%–83.0% specific for MCI
  • Unknown optimal cut points

Memory Impairment Screen

Brief psychometric delayed and cued recall test

  • Examiner administers to patient
  • Score range: 0–8; ≤4, possible cognitive impairment
  • Takes 4 min
  • Forty-three percent–86% sensitive and 93%–97% specific for dementia
  • Works for visually impaired (no writing or drawing component)

Mini-Cog

Psychometric test of memory, executive function, language, and praxis using clock draw and 3-word recall test

  • Examiner administers to patient
  • Score range 0–5; higher score c/w less cognitive impairment
  • Takes 3–4 min
  • Seventy-six percent–one hundred percent sensitive and 54%–85% specific for dementia
  • Low sensitivity for MCI
  • May perform better in low-education populations

Mental State Examination

Psychometric test of memory, attention, orientation, language, and praxis

  • Examiner administers to patient
  • Score range: 0–30; 21–24, mild dementia; 13–20, moderate dementia; 3-point change considered clinically significant
  • Takes 7–10 min
  • 88.3% sensitive and 86.2% specific for dementia with a cut point of 23/24 or 24/25
  • Limited sensitivity and specificity for MCI
  • Has copyright restrictions

Montreal Cognitive Assessment

Psychometric test of memory, executive function, language, and praxis; designed to detect mild cognitive impairment

  • Examiner administers to patient
  • Score range 0–30; higher score c/w less cognitive impairment
  • Takes 10 min
  • Eighty percent to one hundred% sensitive and 50%–76% specific for mild cognitive impairment using a cut point of 25/26

Neuropsychiatric Inventory Questionnaire

Informant questionnaire on twelve behavioral symptoms (items are yes/no; yes, answers get 1–3 severity rating) and caregiver distress (1–5)

  • Informant self-administers
  • NPI-Q severity score range: 0–36. NPI-Q distress score: 0–60; higher scores c/w more severe behavioral symptoms and caregiver distress
  • It takes 5 minutes to administer
  • Must have a reliable informant
  • Assesses for behavioral symptoms associated with multiple dementia syndromes

Data from Lin, J. S., et al. Screening for cognitive impairment in older adults: A systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013 159(9): 601-612.

Author: Lauren McCollum, MD

Penn Memory Center, University of Pennsylvania, Philadelphia, PA, USA

McCollum L, Karlawish J. Cognitive Impairment Evaluation and Management. Med Clin North Am. 2020;104(5):807-825. doi:10.1016/j.mcna.2020.06.007
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