Symptoms and signs of the common causes of dementia are detailed in Table 24–6. Clinicians should be aware that a patient’s insight into a cognitive change may be vague or absent, and collateral history is essential to a proper evaluation. As patients age, primary care clinicians should inquire periodically about the presence of any cognitive symptoms.
Symptoms depend on the area of the brain affected. Short-term memory loss, involving the repeating of questions or stories and a diminished ability to recall the details of recent conversations or events, frequently results from pathologic changes in the hippocampus. Word-finding difficulty often involves difficulty recalling the names of people, places, or objects, with low-frequency words affected first, eventually resulting in speech laden with pronouns and circumlocutions. This problem is thought to arise from pathology at the temporoparietal junction of the left hemisphere. Problems with articulation, fluency, comprehension, or word meaning are anatomically distinct and less common. Visuospatial dysfunction may result in poor navigation and getting lost in familiar places, impaired recognition of previously familiar faces and buildings, or trouble discerning an object against a background. The right parietal lobe is one of the brain areas implicated in such symptoms. Executive dysfunction may manifest by easy distractibility, impulsivity, mental inflexibility, concrete thought, slowed processing speed, poor planning and organization, or impaired judgment. Localization may vary and could include the frontal lobes or subcortical areas like the basal ganglia or cerebral white matter. Apathy or indifference, separate from depression, is common and may have a similar anatomy as executive dysfunction. Apraxia, or the loss of learned motor behaviors, may result from dysfunction of the frontal or parietal lobes, especially the left parietal lobe.
The time of symptom onset must be established, but subtle, early symptoms are often apparent only in retrospect. Another event, such as an illness or hospitalization, may lead to new recognition of existing symptoms. Symptoms often accumulate over time, and the nature of the earliest symptom is most helpful in forming the differential diagnosis. The history should establish risk factors for dementia, including family history, other chronic illnesses, and vascular disease risk factors. Finally, it is important to document the patient’s current capacity to perform basic and instrumental activities of daily living (see Chapter 4) and to note the extent of decline from the premorbid level of function. Indeed, it is this functional assessment that defines the presence and severity of dementia.
The physical examination is important to identify any occult medical illness. In addition, eye movement abnormalities, parkinsonism, or other motor abnormalities may help identify an underlying neurologic condition. The workup should prioritize the exclusion of conditions that are reversible or require separate therapy. Screening for depression is necessary, along with imaging and laboratory workup, as indicated below.
B. Neuropsychological Assessment
Brief quantification of cognitive impairment is indicated in a patient complaining of cognitive symptoms or if caregivers raise similar concerns. The Folstein Mini Mental State Exam (MMSE), Montreal Cognitive Assessment (MoCA), Mini-Cog, and other similar tests are brief, objective, and widely used but have important limitations: they are insensitive to mild cognitive impairment, they may be biased negatively by the presence of language or attention problems, and they do not correlate with functional capacity.
A neuropsychiatric evaluation by a trained neuropsychologist or psychometrician may be appropriate. The goal of such testing is to enhance localization by defining the cognitive domains that are impaired as well as to quantify the degree of impairment. There is no standard battery of tests, but a variety of metrics is commonly used to assess the symptom types highlighted above. Assessments are most accurate when a patient is well rested, comfortable, and otherwise medically stable.
In an asymptomatic patient, there is no screening guideline. Because occult cognitive impairment can lead to morbidity through isolation and poor attentiveness to basic needs (for instance, in an elderly individual living alone), periodic screening is prudent for patients in their 70s and older, for instance with the Mini-Cog: Ask the patient to repeat three simple nouns (not referring to objects in the room), then to draw a clock face with numbers in the correct place and the hands indicating a time of “ten past eleven,” and finally to recall the three nouns; recall of fewer than three words or any abnormality in the clock drawing may signify a need for more in-depth screening (MMSE or MoCA) and further workup (ie, laboratory testing and imaging).
Brain imaging with MRI or CT without contrast is indicated in any patient with a new, progressive cognitive complaint. The goal is to exclude occult cerebrovascular disease, tumor, or other identifiable structural abnormality, rather than to provide positive evidence of a neurodegenerative disease. Global or focal brain atrophy may be worse than expected for age and could suggest a particular neurodegenerative process, but such findings are rarely specific.
PET with fluorodeoxyglucose (FDG) does not confirm or exclude any specific cause of dementia but may be useful as an element of the workup in specific clinical circumstances, such as discriminating between Alzheimer disease and frontotemporal dementia in a patient with some symptoms of each. PET imaging with a radiolabeled ligand for beta-amyloid, one of the pathologic proteins in Alzheimer disease, is highly sensitive to amyloid pathology and may provide positive evidence for Alzheimer disease in a patient with cognitive decline. However, after age 60 or 70, amyloid plaques can accumulate in the absence of cognitive impairment; thus, the specificity of a positive amyloid scan diminishes with age. Single-photon emission computed tomography offers similar information as FDG-PET but is less sensitive. PET imaging with radiolabeled ligands for tau, a pathogenic protein in Alzheimer disease, progressive supranuclear palsy, and some forms of frontotemporal dementia, also may help refine premortem diagnostic accuracy.
Serum levels of vitamin B12, free T4, and thyroid-stimulating hormone should be measured for any patient with cognitive symptoms. A serum rapid plasma reagin (RPR) and testing for HIV should be considered. Other testing should be driven by clinical suspicion, and often includes a complete blood count, serum electrolytes, glucose, and lipid profile.
Although the presence of one or two ApoE epsilon-4 alleles indicates an increased risk of Alzheimer disease and ApoE genotyping is clinically available, it is of limited clinical utility. Finding an ApoE epsilon-4 allele in a young patient with dementia might raise the index of suspicion for Alzheimer disease, but obtaining a genotype in an elderly patient is unlikely to be helpful, and doing so in an asymptomatic patient as a marker of risk for Alzheimer disease is inappropriate until a preventive therapy becomes available. Spinal fluid protein measurements are also available; levels of beta-amyloid decrease and tau protein increase in Alzheimer disease, but this testing shares some of the same concerns as amyloid PET imaging.