Screening for Cognitive Impairment

Background

Screening for dementia and other cognitive impairments is increasingly important as our population ages. However, controversy exists as to who should be screened, when, where, by whom, and with what instruments. Considering the sensitivity, specificity, positive predictive value, and negative predictive value of available screening instruments, treatments available (or not) for the conditions for which patients are being screened, and risks of false positive or false negative results is important. ^{[1, 2, 3, 4]}

An image depicting temporospatial EEG characteristics can be seen below.

Cognitive decline is associated with alterations in the temporospatial EEG characteristics, specifically seen as a decline in resting alpha frequency. However, these findings are non-specific, and medication effects must be ruled out.

Indication

The American Academy of Neurology suggests cognitive screening when cognitive impairment is suspected. ^[5]  In 2020, the US Preventive Services Task Force (USPSTF) concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening for cognitive impairment in older adults. ^[6]

Contraindication

Certain cognitive screening tests cannot be used with patients who have various handicaps, for example, aphasia or physical limitations in their ability to write.

Preparation

Optimally, cognitive screening tests that are used have sufficiently high sensitivity, specificity, and positive predictive value. False positive results and the attendant emotional distress represent a potential complication. For this reason, young and healthy patients in whom no reason exists to suspect a cognitive disorder should not have a cognitive screen performed.

Approach

Several tools are available for cognitive screening in the physician’s office. These tests ideally would have the following characteristics: ^[1]

• Short administration time

• Appropriate sensitivity and specificity for different patient demographics (including sex, age, education level, race, and ethnicity)

• Appropriate sensitivity and specificity for different cognitive disorders

• Screening of various neuropsychological abilities

The Mini-Mental State Examination (MMSE) is the most commonly used cognitive screen and has reasonable sensitivity and specificity for dementia (77% and 90%, respectively, in high-prevalence specialist settings, and 81% and 87%, respectively, in low-prevalence settings). ^[7] One meta-analysis concluded that for screening, if the duration of test is not a major consideration, then the MMSE is the best choice for primary care clinicians who want both a rule-in and rule-out tool. ^[8] However, some primary care physicians find it impractical because of its length of administration. ^[9] Especially in settings in which a higher than community baseline prevalence of dementia exists, the 6 Item Screen and Mini-Cog are quicker and as accurate as the MMSE. ^[8]

Available screening tools that are commonly used and have reasonable sensitivity and specificity in primary care populations, along with the specific characteristics of each one, are described in the Table below. Characteristics of more brief screening tools for dementia are available in Mitchell and Malladi’s recent meta-analysis. ^[8]

Table. Screening Tools (Open Table in a new window)

Long-term monitoring

Once dementia or other cognitive impairment has been diagnosed, re-evaluation at intermittent times in the future may be helpful. This may include re-administration of brief cognitive screens or of more thorough neuropsychological tests. Quantification of the level of impairment may have treatment implications. For example, certain medications used for Alzheimer Disease are only approved for use in certain severities of illness. Moreover, follow-up testing may provide helpful information when results are equivocal, as further decline in between tests is suggestive of cognitive impairment. ^[18]

Patient education

Patients diagnosed with dementia and their family members should be educated about the disorder by clinicians involved in their care. Topics to be addressed include the following:

• The specific type of dementia diagnosed and risk factors for it

• Current symptoms attributable to the disorder

• Natural history and prognosis of the disorder

• Medication treatments

• Psychosocial treatments

• Safety and lifestyle issues, including driving, cooking, wandering, and falls

• Health care decision making

• The need for caregiver support

Useful websites to which to refer patients and families include:

• National Institute on Aging (The Alzheimer’s Disease Education and Referral Center)

• Medscape Alzheimer’s Disease Resource Center

• National Alliance for Caregiving

• U.S. National Institutes of Health National Institute on Aging

A helpful book for families with a loved one with dementia is The 36-Hour Day: A Family Guide to Caring for Persons with Alzheimer disease, Related Dementing Illnesses, and Memory Loss in Later Life (Nancy L. Mace and Peter V. Rabins).

Diagnostic testing summary

If clinical history and a cognitive screen suggest cognitive impairment, then further diagnostic assessment and testing is often performed. The following assessments help to rule out treatable causes of cognitive impairment and to delineate exact causes of dementia:

• Drug history, including substances of abuse as well as medications (especially analgesics, anticholinergics, and sedative-hypnotics). ^[19]

• A thorough physical examination, including a neurological examination.

• Laboratory testing. The American Academy of Neurology recommends screening for B12 deficiency and hypothyroidism in patients diagnosed with dementia. ^[20] Additionally, clinicians may order laboratory tests to assess complete blood count, electrolytes, glucose, renal and liver function tests, neurosyphilis status, folate, urinalysis, ESR, ANA, CRP, HIV, Lyme, copper, ceruloplasmin, and heavy metal screen. At this time, genetic testing of any sort is not recommended to screen for dementia or for specific causes of it.

• Other diagnostic tests may be ordered depending on clinical picture: brain MRI, PET, SPECT, lumbar puncture, EEG, and brain biopsy.

• Neuropsychological testing. A cognitive screen, designed to occur during brief appointments and often in the primary care setting, is not a substitute for a full neuropsychological assessment in uncertain cases. This more thorough evaluation can sometimes help to delineate subtypes of dementia and uses comprehensive screening instruments to examine attention/working memory, new verbal learning and recall, expressive language, visual construction, executive function, and abstract reasoning. ^[1]

• Screening for depression, which may masquerade as dementia

Medication summary

No medications are used in the process of screening for cognitive impairment. However, if dementia is diagnosed, medications may be used to treat the symptoms of the condition or to slow down progression of it. The following are among the most common medications that may be used: ^[21]

• Cholinesterase inhibitors (tacrine, donepezil, rivastigmine, and galantamine): These medications are approved for use in mild, moderate, or severe Alzheimer disease and are sometimes also used for other types of dementia (for example, vascular dementia or mixed dementias). These medications may produce small, temporary improvements in cognition or functioning or temporarily slow down cognitive decline.

• Memantine: This medication is an N-methyl-D-aspartate receptor antagonist. It is approved to treat moderate to severe Alzheimer disease. Additionally, memantine together with a cholinesterase inhibitor is a combination sometimes used in moderate to severe Alzheimer disease. The clinical effect of memantine is like that of the cholinesterase inhibitors in that it may result in temporary benefit but does not change the long-term course of the disorder.

• Other medications that may be used to manage the symptoms of dementia include antidepressants/anxiolytics (eg, fluoxetine, sertraline, paroxetine, citalopram), antipsychotics (eg, haloperidol, risperidone, quetiapine, olanzapine, ziprasidone), and anticonvulsants (eg, valproic acid, carbamazepine, gabapentin, lamotrigine). However, none of these are specifically FDA-approved for use in dementia. Furthermore, atypical antipsychotics have a black box warning stating that their use in elderly patients with dementia-related psychosis is associated with an increased risk of death compared to placebo. Most such deaths appear to be either cardiovascular (eg, heart failure, sudden cardiac death) or infectious (eg, pneumonia) in nature. The decision to use atypical antipsychotics in patients with dementia must involve a careful weighing of potential risks and benefits.

Nonmedication behavioral interventions

Emotional and psychological disturbances affect up to 90% of individuals with Alzheimer disease and cause significant distress both for them and their caregivers. Behavioral interventions to control these symptoms should always be tried before medications. Such interventions include redirecting the patient, distraction techniques, and soothing music. Novel environments can precipitate agitated behavior and should be avoided if reasonably possible. Additionally, some studies show that exercise not only slows cognitive decline and improves function in people with dementia, but also reduces episodes of agitated behavior and improves sleep. ^[22]

Future direction

Physicians currently do not have available rigorous treatment options that change the natural course of dementia. However, if and when interventions to prevent, delay, or cure dementia become available, then early identification will become more important. Cognitive screens of increased sensitivity, specificity, positive predictive value, and negative predictive value that can be easily and quickly administered in a variety of clinical settings will be paramount. From population health and economic perspectives, in order to do the most good for the greatest number of people, economically viable screening methods must be developed. These might include, for example, cognitive screening examinations rather than expensive neuroimaging or serum analysis. ^[23]