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Frequent Amyloid Deposition Without Significant Cognitive Impairment Among the Elderly
Howard Jay Aizenstein, MD, PhD;
Robert D. Nebes, PhD;
Judith A. Saxton, PhD;
Julie C. Price, PhD;
Chester A. Mathis, PhD;
Nicholas D. Tsopelas, MD;
Scott K. Ziolko, MS;
Jeffrey A. James, BS;
Beth E. Snitz, PhD;
Patricia R. Houck, MS;
Wenzhu Bi, MS;
Ann D. Cohen, PhD;
Brian J. Lopresti, BS;
Steven T. DeKosky, MD;
Edythe M. Halligan, MA;
William E. Klunk, MD, PhD
Arch Neurol. 2008;65(11):1509-1517.
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.
Author Affiliations: Departments of Psychiatry (Drs Aizenstein, Nebes, Tsopelas, Cohen, and Klunk and Mss Houck and Halligan), Neurology (Drs Saxton, Snitz, DeKosky, and Klunk), and Radiology (Drs Price and Mathis and Messrs Ziolko, James, Bi, and Lopresti), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
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