Neuropsychologic Approaches to Dementia

When the question of possible cognitive decline arises, international guidelines recommend a multifaceted approach to rule out potentially reversible conditions before diagnosing neurodegeneration.¹ Blood tests, neuroimaging, and analysis of cerebrospinal fluid biomarkers are common first steps. Importantly, although those tests assist with differential diagnosis, none characterize cognition. Cognitive screening measures (eg, Mini-Mental State Examination [MMSE])² provide a basic indication of impairment severity. Scores on those measures, however, do not distinguish among different dementia syndromes, can overpathologize those with limited education, and can be insensitive to change among adults with advanced education. A neuropsychologic evaluation objectively assesses cognitive abilities using valid, reliable, standardized measures. In essence, performance on those measures informs how the brain is actually functioning. That information can be used in combination with other test results to more thoroughly inform differential diagnoses among the many causes of dementia.³

Evidenced-Basis for Neuropsychologic Evaluation in Dementia

There is strong evidence for the incremental value of neuropsychologic test performance in predicting neurodegenerative disease outcomes beyond demographic, genetic, neuroimaging, and serum biomarkers.⁴ Performance on measures of delayed recall for paragraph-length information and word lists, together with neuroimaging data, significantly predicts progression from mild cognitive impairment (MCI) to dementia over a 2-year period, above and beyond various genetic and biologic markers.⁵ Although neurodiagnostic data (eg, fluorodeoxyglucose [FDG] positron emission tomography [PET]) is a strong independent predictor of progression from MCI to Alzheimer disease (AD), the best multivariate model includes both PET findings and performance on measures of delayed verbal memory.⁶ A composite measure of overall performance on verbal fluency, learning and memory, and executive functioning can be more sensitive to disease progression than hippocampal atrophy or cortical thickness measured with neuroimaging.⁷

Neuropsychologic evaluation can help identify early stages of dementia that may otherwise be missed (Case 1). Importantly, MCI diagnostic criteria based on comprehensive neuropsychologic variables significantly reduced the rate of false negative diagnostic errors compared with conventional dementia diagnostic criteria (eg, subjective memory complaints, clinical interviews, cognitive screening, and impairment on 1 objective memory measure).^8,9 Neuropsychologic evaluation can also help reduce the risk of false positive errors, in which cognitive complaints are inaccurately diagnosed as dementia when these may in fact be caused by something else (eg, clinically significant depression). This helps avoid iatrogenic harm to those who might make different life decisions if diagnosed with a treatable condition rather than a neurodegenerative disease.

Referral Process

Most neuropsychologists work within various departments of medical institutions (eg, psychiatry, neurology, or neurosurgery). Physical location can affect how readily neuropsychologists integrate with other services (eg, some memory clinics have neuropsychologists on site, whereas others refer out for those services). Referrals to neuropsychology occur for several reasons (Box),¹⁰ and can be especially useful in cases of suspected early-onset dementia, in which a person may be denied disability if objective evidence of impairment is not provided.

Similar to when referrals are made to neurology, it is helpful to write a specific referral question (eg, is a person’s cognitive concern a sequelae of a mood disorder vs a neurodegenerative process?) so the neuropsychologist can thoroughly capture particular areas of concern. If there is unclear benefit of neuropsychologic evaluation, providers are encouraged to reach out directly to a neuropsychologist to review the case.

Neuropsychologic Evaluation Procedures

Clinical neuropsychologic evaluations include an in-depth clinical interview with the patient and preferably also a family member, objective cognitive assessment, and feedback of test results and clinical impressions. The latter often occurs as a separate appointment. Appointment lengths vary depending on the referral question and can range from 2 to 8 hours.¹¹

Clinical Interview

The clinical interview serves to clarify the cognitive, physical, behavioral, and psychologic symptoms that a person has experienced. Temporal onset, course of symptoms, and impact on everyday functioning are assessed.¹² The interview also allows assessment of potentially reversible risk factors that may be contributing to an individual’s cognitive complaints, (eg, specific psychosocial stressors or chronic headaches). Collateral interviews with reliable informants may reveal information that is consistent or discrepant with patient report, which is particularly important in the assessment of dementia since anosognosia and difficulty with temporal organization may be part of the clinical presentation (Case 2).

Assessment

The Table presents common neuropsychologic tests by domain.¹³ Most neuropsychologists use a flexible evaluation approach with a fairly standard set of measures. Adjustments may be made based on referral question, impairment severity, and individual test performance.¹⁴ Assessed cognitive domains include attention and processing speed, language, visuospatial and constructional abilities, memory, and executive functioning. Fine motor abilities and other functions (eg, simultanagnosia) may be assessed. Typically, 2 tests are administered per domain to maximize reliability of findings; each test contains numerous items for that reason.¹³ The overall pattern of results is interpreted within the broader context of the individual’s clinical presentation. Mood is routinely assessed, at a minimum via clinical interview, but often via standardized questionnaires or even an in-depth personality measure, when appropriate. This is important because it helps to inform differential diagnosis and can also inform quality of life. Behavior rating inventories are commonly used, including family-report measures, which can be particularly helpful in conditions with primarily behavioral manifestations (eg, FTD-behavioral variant).

Interpretation

Each test is interpreted in the context of demographically corrected normative data from the test publisher or other researchers. Comparison to the individual’s estimated intellectual baseline is an important part of interpretation because individuals may fall anywhere on the normal distribution in terms of general cognitive ability, and change from baseline is how decline is determined. Baseline is estimated using educational attainment, employment history, and performance on measures less susceptible to cognitive decline (eg, word-reading test).¹⁴ Test-score validity is assessed with objective indicators embedded in individual tests or using stand-alone measures.¹⁴ The entire neuropsychologic profile is interpreted within a person’s broader presentation and clinical history. In summary, test scores alone are insufficient to determine if a cognitive disorder is present and must be used in tandem with other types of data to elucidate the underlying etiology.

Results and Recommendations

Neuropsychologists integrate information from the evaluation and medical record into a comprehensive report submitted to the referring provider. The report typically indicates whether psychometric criteria for a neurocognitive disorder (NCD) as specified in the Diagnostic and Statistical Manual of Mental Disorders (DSM5) are present.¹⁵ Mild NCD is similar to MCI because it requires evidence of measurable decline in 1 or more cognitive domains but preserved everyday functioning. Prognosis, however, depends on the underlying etiology (eg, a neurodegenerative process vs a traumatic brain injury). Major NCD (ie, dementia) requires significant decline in 1 or more cognitive domains that interfere with activities of daily living. Differential diagnoses are typically listed when known. Otherwise, risk factors may be listed instead.

Research has identified modifiable risk factors that can negatively affect cognition, including a sedentary lifestyle, emotional distress, poor sleep, medication side effects, substance use, or poor diet.^16,17 Having multiple risk factors is associated with greater likelihood of cognitive decline.¹⁷ Treatment recom-mendations addressing reversible risk factors may include referral for additional services, (eg, a formal driving evaluation by an occupational therapist or medication reconciliation secondary to high anticholinergic burden). The goal of the recommendations is to maximize function and outcomes. Psychoeducation for compensatory strategies is also common.¹⁸ These recommendations may include strategies like developing a routine around tasks and using external cues (eg, alarms, pillboxes, and calendars). Earlier in the dementia process, persons with dementia may be able to take preparatory steps to maximize function. Later in the disease progress, family members may be educated on strategies to help reduce confusion and frustration (eg, keeping a calendar in a highly visible place in the home like the phone and redirecting conversations). Family members can be encouraged to obtain durable power of attorney to better assist with medical and financial decision making.

Repeat Evaluation

Repeat neuropsychologic evaluations can be used to monitor course of disease progression and to update recommendations. Common methods to assess change include reliable change indices and standardized regression-based models.¹⁹ These methods statistically control for test-retest effects and measurement error, so one may infer whether factors like progression of illness or changes in modifiable factors are associated with improvement or deterioration of cognitive functioning.

Special Considerations & Potential Limitations

Cognitive assessments for individuals with sensory disabilities (eg, vision or hearing impairment) or physical limitations (eg, severe upper extremity tremor) can challenge standardized testing procedures.²⁰ Fortunately, comprehensive evaluations can be tailored to accommodate such individuals through test selection and sometimes even modifications. Neuropsychologists know their instruments exceptionally well and have a wide range of tests at their disposal; they can readily make inferences about which test results will provide the most accurate results given any limitations of an individual patient.

Another special consideration is assessment of persons from culturally diverse backgrounds. Language is a central component of a valid cognitive assessment and can influence the accuracy of results. Most cognitive tests are based on Western societies and may not reflect the values, knowledge, and experiences of culturally diverse people, making the tests subject to measurement bias that cannot be easily rectified through interpretation or translation.²¹ An informed neuropsychologist will make every effort to minimize cross-cultural barriers (eg, maximizing comfort of test environment and selecting tests with less measurement bias or that are appropriately translated and validated for use in non-English speaking populations).

Performance validity must be addressed for all cognitive assessments. Determining whether an individual exhibits credible performance must be objectively measured throughout the evaluation with embedded and stand-alone measures of performance validity. Failure of 2 or more performance validity indicators reliably discriminates between credible and noncredible cognitive profiles.²² Scores showing impairment on performance validity measures can occur for many reasons, including severe emotional distress or failure to grasp the purpose of the neuropsychologic evaluation; failure on these measures often does not necessarily imply intentional feigning or malingering.

Thinking Ahead

Medicine is increasingly shifting toward collaborative person-centered care. Numerous established guidelines now include neuropsychologists as key members of interdisciplinary teams considering their expertise in cognition and behavior. It is therefore unsurprising that almost half of neuropsychologists are members of more than 1 interdisciplinary team.²³ With more active communication and teamwork, neuropsychologists can better understand how to be most beneficial to the patient and team. Increased diagnostic precision and collaborative research are also more likely under these circumstances and can enhance academic missions and clinical services.