Neuropsychology in the Diagnosis and Treatment of Dementia

Introduction

The aging of the U.S. baby boomer population has given rise to a significant increase in the prevalence of Alzheimer disease, the most common form of dementia in adults older than 65 years. One in three Americans aged 85 and older has Alzheimer disease, and by 2050, up to 16 million are predicted to have Alzheimer disease. Dementia is defined as significant impairment in cog­nitive functioning (serious enough to interfere with daily life) that is not accounted for by other medical conditions. Mild cognitive impairment (MCI) is a condition of significant cognitive deterioration from a presumed higher level without functional impairment, which may be a prodromal stage of dementia. Neuropsychologists can assist in characterizing cognitive loss and providing diagnostic differentiation, thereby supporting early detection of cognitive change in individuals with dementia. Despite the fact that detection is possible even at early stages, nearly half of older primary care patients remain undiagnosed and untreated, partly because health care providers do not have time or access to assessment and may lack places to refer patients for needed support services. This chapter reviews indications for neuropsychological evaluation, discusses new diagnostic criteria and methods of assessment, and describes how test results can direct treatment planning.

Indications for Neuropsychological Assessment

A neuropsychological evaluation can be helpful in distinguishing pathologic cognitive performance from normal aging by examining patterns of performance across cognitive domains. Signature patterns of cognitive strengths and weaknesses, including assessed activities of daily living (ADLs), may support the diagnosis of specific types of dementia or MCI and may be useful in predicting the course or progression of cognitive disease to help determine whether a patient is safe to live alone or manage his or her finances. This is important because compared with normal controls, those with MCI and dementia have elevated mortality rates.

Changes in Diagnostic Criteria to Detect Milder Impairment

New diagnostic criteria for Alzheimer disease have been proposed, each specifying a slightly different role for neuropsy­chological testing ( Table 51-1 ). The revised diagnostic criteria reflect significant scientific advances in genetics and biomarkers for Alzheimer disease pathology. Evidence that neuropathology may precede symptoms, has led to criteria for presymptomatic stages. The National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria, used primarily to guide research, require the presence of gradual episodic memory impairment confirmed with neuropsychological testing, with supportive features, including the presence of at least one Alzheimer disease biomarker.

The National Institute on Aging–Alzheimer's Association (NIA-AA) provides criteria for Alzheimer disease, MCI, a clinical diagnosis for and a categorization of MCI due to Alzheimer disease used for research, and research guidelines for an asymptomatic, preclinical phase. The criteria for probable Alzheimer disease first require meeting criteria for a general dementia. These criteria require cognitive and behavioral symptoms that (1) interfere with functional abilities or usual activities, (2) represent a decline from previous function, and (3) are not explained by delirium or other psychiatric disorder. Evidence of cognitive impairment can be assessed through clinical examination or by neuropsychological testing and must include impairment in two or more cognitive domains. In the current criteria, attention is brought to a wide range of impairments, including language, visuospatial, and executive deficits, along with mood-related or behavioral symptoms. Special mention is given to language, because expressive aphasias often thought to be focal in nature can progress to be part of a general dementia syndrome. In addition, changes in behavior, personality, and comportment are now considered a “cognitive domain” and can include agitation, apathy, and social withdrawal. Although memory impairment may be the most common deficit, it is not required for the dementia diagnosis. The diagnosis of Alzheimer disease continues to use the distinction of probable and possible Alzheimer disease to rate the level of confidence based on clinical presentation. Probable Alzheimer disease has four criteria: three of inclusion (slow, insidious onset; evidence of worsening of cognition; and at least one amnestic or nonamnestic cognitive deficit) and one of exclusion (the presence of vascular disease or other dementia). NIA-AA recommends that comprehensive neuropsychological testing be used in complicated cases when a standard office exam and cognitive screen such as the Mini Mental State Examination (MMSE) are not sufficient to provide a clear diagnosis.

The NIA-AA defined core clinical criteria for a diagnosis of MCI described by Albert et al. These criteria include (1) cognitive complaint or cognitive problems suspected by family, friend, or care provider; (2) impairment in one or more cognitive domains; (3) relative independence in functional abilities; and (4) not demented. The diagnosis of MCI due to Alzheimer disease, often used in research, requires biomarker evidence of neurodegeneration, or amyloid or tau accumulation.

The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), provides definitions for major and mild neurocognitive disorders (NCDs). Diagnostic criteria require evidence of a cognitive decline (“significant” for major and “modest” for mild) from a previous level of functioning in one or more cognitive areas (e.g., memory, executive functioning) based on report by the patient or family and “preferably” documented by neuropsychological test performance. Functional decline is required for major NCD, defined as needing help with everyday activities such as bill paying or shopping. Functional decline is not required for minor NCD, although extra effort or time may be needed to complete daily activities. Mild NCD captures the diagnosis of MCI (which was previously coded as cognitive disorder not otherwise specified), and the criteria overlap with those for MCI due to Alzheimer disease as outlined in the NIA-AA diagnostic guidelines.

Once criteria for major or mild NCD are met, additional diagnostic criteria are provided to identify specific subtypes classified according to cause (e.g., Alzheimer disease, substance use, human immunodeficiency virus [HIV] infection).

Clinical Interviewing

A clinical interview lays the groundwork for both test selection and interpretation of the neuropsychological results. Informants, often caregivers or family members, are helpful as they can often provide critical information regarding the onset and course of symptoms. Reporting by a person with memory problems may not be accurate, and informant reports have been shown to relate to objective test deficits. Careful questioning can help diagnosticians identify features of specific types of dementia (insidious or precipitous course, falls, significant apathy, profound language decline, sudden behavioral changes ) and other medical conditions that cause cognitive impairment (e.g., sleep apnea, drug and alcohol abuse, depression, misuse of prescription medications).

Screening and Brief Cognitive Assessments in the Diagnosis of Dementia

In the primary care setting, brief screens can help physicians identify those at greatest risk for cognitive impairment (e.g., indicators include age, education, history of stroke, presence of diabetes, depression, and a need for help with finances). In their comprehensive review of brief screening instruments to identify cognitive impairment in older adults, Lin and colleagues identified the following instruments as reliable in the detection of dementia: the MMSE, Clock Drawing Test, Memory Impairment Screen, Abbreviated Mental Test, Short Portable Mental Status Questionnaire, Free and Cued Selective Reminding Test, 7-Minute Screen, Telephone Interview for Cognitive Status, and the Informant Questionnaire on Cognitive Decline in the Elderly.

As a group, these instruments have demonstrated reasonable ability to distinguish normal cognition from dementia, although their ability to distinguish milder states such as MCI from normal aging is inconsistent. However, one recent study found that the Montreal Cognitive Assessment was better at distinguishing normal cognition from MCI than the MMSE.

Patients with suspected dementia or MCI who pass the screen can be referred for full neuropsychological testing that can better capture the subtle effects of MCI.

The challenge is in persuading physicians in primary care, in the context of time constraints and reimbursement issues, of the value of using any of these instruments and of the value of early diagnosis, as it may be difficult to identify the care services of those with positive screens.

In summary, cognitive screening and brief cognitive assessments in the primary care setting can be useful for detecting frank dementia and may be administered by those with a minimal amount of training to identify those in need of further evaluation. In clinical practice, neuropsychological testing remains the most accurate method to identify and characterize very early symptoms and distinguish them from other types of cognitive impairment.