Memory impairment, executive dysfunction, and intellectual decline in preclinical Alzheimer's disease

TLDR

The study aimed to determine when cognitive decline begins in preclinical Alzheimer’s disease by aligning subjects at diagnosis and tracking performance over time. Using data from the Baltimore Longitudinal Study of Aging, the authors examined trajectories of episodic memory, executive function, and verbal intelligence in 92 incident AD cases over up to 15 years before diagnosis. They found episodic memory declined as early as seven years before diagnosis, executive function accelerated 2–3 years prior, while verbal intelligence remained stable until near diagnosis, consistent with earlier involvement of memory‑mediating structures. Supported by NIH grants AG017854, AG08325, AG03949, AG16573 and the National Institute on Aging Intramural Research Program; JINS 2008, 14, 266–278.

Abstract

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.)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.