Memory impairment, executive dysfunction, and intellectual decline in preclinical Alzheimer's disease
In the Baltimore Longitudinal Study of Aging (BLSA), we examined the temporal unfolding of declining performance on tests of episodic memory (Free Recall on the Free and Cued Selective Reminding Test), executive function (Category Fluency, Letter Fluency, and Trails), and Verbal Intelligence (Nelson, 1982; American Version of the Nelson Adult Reading Test [AMNART]) before the diagnosis of dementia in 92 subjects with incident Alzheimer's disease (AD) followed for up to 15 years before diagnosis. To examine the preclinical onset of cognitive decline, we aligned subjects at the time of initial AD diagnosis and examined the cognitive course preceding diagnosis. We found that declines in performance on tests of episodic memory accelerated 7 years before diagnosis. Declining performance on tests of executive function accelerated 2–3 years before diagnosis, and verbal intelligence declined in close proximity to diagnosis. This cognitive profile is compatible with pathologic data suggesting that structures which mediate memory are affected earlier than frontal structures during the preclinical onset of AD. It also supports the view that VIQ as estimated by the AMNART does not decline during the preclinical onset of AD. (JINS, 2008, 14, 266–278.) a(Received March 16 2007)
(Revised October 30 2007)
(Accepted October 31 2007)
Key Words: Alzheimer's disease; Prospective studies; Preclinical dementia; Cognition disorders; Memory disorders; Verbal learning.
c1 Correspondence and reprint requests to: Ellen Grober, Ph.D., Montefiore Medical Center, 111 East 210th Street, Bronx, New York 10467. E-mail: [email protected]
a Supported in part by grants AG017854, AG08325, AG03949, and AG16573 from the National Institutes of Health, and by the National Institute on Aging Intramural Research Program of the National Institutes of Health.