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Preclinical Alzheimer disease

Neuropsychological test performance 1.5 to 8 years prior to onset

From the University of Pittsburgh (Drs. Saxton, Lopez, Newman, and Kuller); HealthSouth Harmarville Rehabilitation Hospital (Dr. Ratcliff), Pittsburgh, PA; University of Washington (Dr. Dulberg), Seattle; and Johns Hopkins University (Drs. Fried and Carlson), Baltimore, MD.

Address correspondence and reprint requests to Dr. Judith Saxton, University of Pittsburgh, Oxford Building, Room 738, Pittsburgh, PA 15213; e-mail: saxtonja{at}msx.upmc.edu

Objective: To determine if individuals ultimately diagnosed with Alzheimer disease (AD) exhibited evidence of cognitive impairment on neuropsychological tests administered between 1.5 years and 8.1 years before dementia onset.

Methods: A total of 693 community-dwelling individuals, part of the Cardiovascular Health Study, completed a neuropsychological test battery in 1991/92. Subjects were followed annually over the next 8 years (median follow-up = 7.4 years). Seventy-two individuals were ultimately diagnosed with AD (median follow-up = 4.5 years): 24 with AD onset 1.5 to 3.4 years after baseline neuropsychological testing, 20 with AD onset 3.5 to 5.0 years after testing, and 28 with onset 5.1 to 8.1 years after testing. A total of 621 individuals remained nondemented throughout the 8 years of follow-up (median follow-up = 7.5 years).

Results: Subjects ultimately diagnosed with AD had poorer scores on baseline neuropsychological measures than subjects who remained nondemented. Although individuals closest to AD onset (i.e., 1.5 to 3.4 years) performed the most poorly, cognitive impairment was detected in individuals who did not develop AD until 5 to 8 years later.

Conclusions: Cognitive changes can be detected well before onset of Alzheimer disease.

Received February 21, 2003. Accepted in final form September 2, 2004.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the December 28 issue to find the title link for this article.

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