The actual diagnostic workup involves several steps — an initial evaluation including a medical history, a mental status evaluation, a clinical examination and laboratory tests — as outlined in the Differential Diagnosis of AD Algorithm appearing below. There is more information on each step below the diagram.
Differential Diagnosis in AD Algorithm*
Multiple cognitive deficits, which include memory impairment and at least one of the following: aphasia, apraxia, agnosia or disturbance in executive functioning. Social or occupational function is also impaired. A diagnosis of dementia should not be made during the course of a delirium. (A dementia and a delirium may both be diagnosed if the dementia is present at times when the delirium is not present.)
Alzheimer’s disease is the most common cause of dementia, accounting for between 50 and 60 percent of all cases, but there are many disorders that can cause or simulate dementia. Many of these are the result of degenerative diseases whose progression, at least at the present time, cannot be arrested. However, several causes of dementia are either potentially reversible or stoppable and may be responsive — either totally or in part — to treatment.
Medication-induced dementia is the most frequent cause of “reversible” dementia. The incidence of adverse drug reactions increases with age. Alterations in pharmacokinetics and pharmacodynamics, together with the presence of concomitant illnesses (especially renal, hepatic and cardiac) and the number of prescribed and over-the-counter medications taken, render older people more vulnerable to adverse events. To rule out a medication-induced dementia, a thorough drug history and a review of all current medication (both prescription and over-the-counter) should be undertaken. The “brown bag” test, wherein patients bring all their medication to the physician for inspection, is essential.
Metabolic / endocrine / nutritional / systemic disorders
Metabolic/endocrine/nutritional/systemic disorders (e.g., hypothyroidism, B12 deficiency and systemic infections) are additional causes of “reversible” dementias and can be diagnosed with routine laboratory tests. Tests recommended include blood count, sedimentation rate (if indicated), electrolytes (including calcium), liver and renal function tests, urinalysis, syphilis serology, B12 levels, thyroid function tests and a toxicity screen (if medical history and the physical exam so indicate). Most of these conditions respond favorably to treatment.
Vascular dementia / hydrocephalus / tumors / hematoma
Vascular dementia (VaD) may arise as a sequel to any form of cerebrovascular disease. VaD is responsible for approximately 20 percent of dementia cases. As a comorbid condition, VaD may worsen the dementia of Alzheimer’s disease. A diagnosis of probable vascular dementia is adapted from the following National Institute of Neurological Disorders and Stroke (NINDS) criteria:
Cerebrovascular disease (CVD) is defined by the presence of focal signs on neurologic examination such as: hemiparesis, facial weakness, Babinski sign, sensory deficit, hemianopia, dysarthria consistent with stroke (with or without history of stroke) and evidence of relevant CVD by brain imaging, including multiple large-vessel infarcts or a single strategically placed infarct (angular gyrus, thalamus, basal forebrain), as well as multiple basal ganglia and white matter lacunas or extensive periventricular white matter lesions, or combinations thereof.
Other criteria include any combination of onset of dementia within three months following a recognized stroke; abrupt deterioration in cognitive functions; or fluctuating, stepwise progression of cognitive deficits.
Normal pressure hydrocephalus, brain tumors and subdural hematoma, the most common of the structural brain lesions, can also present with dementia. Confirmation or exclusion of their presence usually requires a CT or MRI scan.
Depression is another common cause of “reversible” dementia in the geriatric population. Unlike younger individuals, elderly depressed patients may present with cognitive impairment, i.e., confusion, memory disturbance, attention deficits, all of which can be mistaken for dementia. Depression may also coexist with dementia and exacerbate the problem, causing; “excess disability.” A good history and thorough mental-status examination should form the basis for a treatment plan to alleviate primary or secondary impairment from depressive symptoms.
DSM-IV criteria for a diagnosis of depression require that a patient experiences five (or more) of the following symptoms during the same two-week period (every day for most of the day, or nearly every day). At least one of the symptoms is either depressed mood or loss of interest or pleasure.
Depressed mood most of the time, as indicated by either subjective report (e.g., feels sad) or observation by others (e.g., appears tearful).
Diminished interest or pleasure in nearly all activities.
Significant weight loss or weight gain (e.g., more than five percent of body weight in a month) or decrease or increase in appetite.
Insomnia or hypersomnia.
Psychomotor agitation or retardation.
Fatigue or loss of energy.
Feelings of worthlessness or guilt.
Diminished ability to think or concentrate, or indecisiveness.
Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.
must cause clinically significant distress or impairment in social and occupational functioning;
are not due to the direct physiological effects of a substance or a general medical condition;
are not better accounted for by bereavement;
persist for longer than two months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms or psychomotor retardation.
Alzheimer’s disease is progressive, resulting in impairment in cognitive function. The clinical symptoms associated with this disease include memory loss, language disorders, visuospatial impairment and behavioral disturbances. Alzheimer's may present with a variety of symptoms, but difficulties with memory are common to all.
For a diagnosis of probable Alzheimer's, the criteria adapted from the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) include:
Dementia established by examination and objective testing
Deficits in two or more cognitive areas
Progressive worsening of memory and other cognitive functions
No disturbance in consciousness
Onset between ages 40 and 90
Absence of systemic disorders or other brain diseases, which could account for the deficits in memory and cognition, should also be established. Atypical cases of dementia should be referred to specialists for assessment.
This list below identifies sources for the Differential Diagnosis of Alzheimer’s Disease Algorithm diagnostic toolbox. Most of these resources can be found by calling your local library, contacting the publisher or calling the Alzheimer’s Association’s Green-Field Library at 312.335.9602.
Mini-Mental Status Examination
Folstein, M.F., Folstein, S.E., and McHugh P.R. “Mini-Mental State”: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research (November 1975), vol. 12 (3): 189-98.
Cockrell, J. R. and M.F. Folstein. Mini-Mental State Examination (MMSE). Psychopharmacology Bulletin (1988), vol. 24 (4): 689-92. Physical Self-Maintenance Scale
Lawton, M., Brody, E. “Assessment of Older People: Self-Maintaining and Instrumental Activities of Daily Living.” The Gerontologist. 1969, 9:179-86.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Washington, D.C.: American Psychiatric Press, 1994.
For more information call American Psychiatric Press at 1.800.368.5777.
AHRQ Guidelines (Agency for Healthcare Research and Quality)
Costa, P. T. Jr., et al. Early identification of Alzheimer’s disease and related dementias. Clinical practice guidelines, quick reference guide for clinicians, no. 19. Rockville, Md.: U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1996.
American Academy of Neurology (AAN) Guidelines
American Academy of Neurology. Practice parameters for detection, diagnosis, and management of dementia (summary statements). Neurology (May 8, 2001), vol. 56: 1133-1142, 1143-1153, 1154-1166
National Institute of Neurological Disorders and Stroke (NINDS) Criteria
Roman, G. C., et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN international workshop. Neurology (February 1993), vol. 43 (2): 250-60.
National Institute of Neurological Communicative Disorders and Stroke (NINCDS) and the Alzheimer Disease and Related Disorders Association Criteria
McKhann, G., et al. Mental and clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology (July 1984), vol. 34 (7): 939-44.