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

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.

Fig. 1

Spaghetti plot for the sum of free recall as a function of time before diagnosis for the 92 incident Alzheimer’s disease cases.

Fig. 2

Profile likelihood values for the first change point in free recall. The maximum value of the graph occurs at 7.1 years before diagnosis and is the value for the first change point best supported by the data.

Fig. 3

Spaghetti plot for category fluency (sum of the number of fruits, animals, and vegetables named in 60 s for each of the three categories) as a function of time before diagnosis.

Fig. 4

Spaghetti plot for letter fluency (sum of the number of words beginning with “f,” “a,” and “s” named in 60 s for each of the three categories) as a function of time before diagnosis.

Fig. 5

Spaghetti plot for Trailmaking B speed, the reciprocal of elapsed time, as a function of time before diagnosis.

Fig. 6

Spaghetti plot of estimated verbal IQ as a function of time before diagnosis.