Frequent amyloid deposition without significant cognitive impairment among the elderly

Abstract

Objective: To characterize the prevalence of amyloid deposition in a clinically unimpaired elderly population, as assessed by Pittsburgh Compound B (PiB) positron emission tomography (PET) imaging, and its relationship to cognitive function, measured with a battery of neuropsychological tests.

Design: Subjects underwent cognitive testing and PiB PET imaging (15 mCi for 90 minutes with an ECAT HR+ scanner). Logan graphical analysis was applied to estimate regional PiB retention distribution volume, normalized to a cerebellar reference region volume, to yield distribution volume ratios (DVRs).

Setting: University medical center.

Participants: From a community-based sample of volunteers, 43 participants aged 65 to 88 years who did not meet diagnostic criteria for Alzheimer disease or mild cognitive impairment were included.

Main outcome measures: Regional PiB retention and cognitive test performance.

Results: Of 43 clinically unimpaired elderly persons imaged, 9 (21%) showed evidence of early amyloid deposition in at least 1 brain area using an objectively determined DVR cutoff. Demographic characteristics did not differ significantly between amyloid-positive and amyloid-negative participants, and neurocognitive performance was not significantly worse among amyloid-positive compared with amyloid-negative participants.

Conclusions: Amyloid deposition can be identified among cognitively normal elderly persons during life, and the prevalence of asymptomatic amyloid deposition may be similar to that of symptomatic amyloid deposition. In this group of participants without clinically significant impairment, amyloid deposition was not associated with worse cognitive function, suggesting that an elderly person with a significant amyloid burden can remain cognitively normal. However, this finding is based on relatively small numbers and needs to be replicated in larger cohorts. Longitudinal follow-up of these subjects will be required to support the potential of PiB imaging to identify preclinical Alzheimer disease, or, alternatively, to show that amyloid deposition is not sufficient to cause Alzheimer disease within some specified period.

Figure 1

Pittsburgh Compound B (PiB) retention among clinically unimpaired controls (red circles) and patients with Alzheimer disease (blue squares). Filled circles indicate apolipoprotein E ε4 carriers in the control group. Red boxes indicate the range of PiB retention among controls aged 55 years and younger. The black and white horizontal bars indicate the amyloid-positive cutoff points in each brain area (see the “Methods” section for explanation). The width of the bar indicates the “intermediate” zone 2.5% above and below the cutoff value that was used to more conservatively categorize amyloid-positive and amyloid-negative participants. ACG indicates anterior cingulate gyrus; AVS, anterior ventral striatum; DVR, distribution volume ratio; FRC, frontal cortex; GBL6, mean of values for FRC, ACG, PRC, AVS, LTC, and PAR regions; LTC, lateral temporal cortex; MTC, mesial temporal cortex; OCC, occipital cortex (includes primary visual cortex); PAR, parietal cortex; PRC/PCG, precuneus cortex/posterior cingulate gyrus; SMC, sensorimotor cortex.

Figure 2

A, Mean distribution volume ratio (DVR) images for 29 amyloid-negative clinically unimpaired participants (left), 9 amyloid-positive clinically unimpaired participants (center), and 9 patients with Alzheimer disease (AD) (right). B, Images obtained by subtracting the amyloid-negative mean image from either the mean of amyloid-positive elderly participants (left) or the mean of patients with AD (right) or by subtracting the amyloid-positive mean image from the mean image of patients with AD (center). The gray background is not a magnetic resonance image but represents Pittsburgh Compound B (PiB) retention differences of less than 0.5 DVR units and is shown for orientation. C, Statistical parametric mapping (SPM) software image of t values was determined from the comparison of the amyloid-negative group with the amyloid-positive clinically unimpaired group (left) or the patients with AD (right).