Cognitive Decline Likely Precedes Alzheimer's Disease Diagnosis

Depressive symptoms may increase during the time before diagnosis, while neuropsychiatric symptoms remain stable.



BOSTON—Patients who are subsequently diagnosed with Alzheimer’s disease may be more likely to have worsening cognitive decline, functional impairment, and depression approximately one to three years before diagnosis than people who never receive a diagnosis of Alzheimer’s disease, researchers reported at the 2012 Annual Meeting of the American Neurological Association.

Depressive symptoms appear to increase among patients who subsequently receive this diagnosis, although other neuropsychiatric symptoms appear to remain stable. Depressive symptoms could result from an individual’s recognition of his or her memory loss and functional decline, said Joseph E. Gaugler, PhD, Associate Professor in the School of Nursing at the University of Minnesota in Minneapolis.

A National Database of Patients With Alzheimer’s Disease
Dr. Gaugler and his colleagues analyzed information from the National Alzheimer’s Coordinating Center’s Uniform Data Survey, which contains cognitive, behavioral, and functional data for each patient who has regularly visited any of the country’s Alzheimer’s Disease Centers from 2005 to the present. The investigators identified a sample of 2,478 participants, including 139 who eventually received a diagnosis of probable Alzheimer’s disease, 109 patients who eventually received a diagnosis of possible Alzheimer’s disease, and 2,230 patients with no diagnosis of Alzheimer’s disease.

Cognitive outcomes were measured by various tests, including the Clinical Dementia Rating and the Mini-Mental State Exam (MMSE). Neuropsychiatric outcomes were measured by the Neuropsychiatry Inventory Questionnaire and the Geriatric Depression Scale. Functional outcomes were evaluated with the Functional Assessment Questionnaire.

Dr. Gaugler’s team created a multilevel change model to estimate patients’ clinical trajectories and to test for differences in them. The researchers adjusted the models for baseline covariates such as age, gender, marital status, and living arrangement.

Cognition Deteriorates Before Alzheimer’s Disease Diagnosis
The results of the Clinical Dementia Rating, MMSE, Trail Making Test, and Digit Span Forward and Backward subscales changed significantly in the time before a diagnosis of Alzheimer’s disease. Controls did not have similar declines.

The researchers noted that diagnoses at Alzheimer’s Disease Centers may be more comprehensive than they are in routine practice, and this difference could limit the significance of the analysis. In addition, participants at the centers are not representative of the population of older adults with or without Alzheimer’s disease in the United States, according to the investigators.

“Our study appears to suggest that declines in function or depressive symptoms occur in tandem with cognitive declines before a formal Alzheimer’s disease diagnosis,” Dr. Gaugler told Neurology Reviews. “While these changes are statistically significant, it remains to be determined whether such changes are clinically significant and detectable to motivate an earlier diagnosis of Alzheimer’s disease or related dementia. The constellation of changes across multiple domains—including cognition, depressive symptoms, and function—taken together may suggest the need for more intensive clinical follow-up on the part of care providers to determine if early-stage dementia is apparent.”

—Erik Greb

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