Cognitive decline and brain volume loss as signatures of cerebral amyloid-beta peptide deposition identified with Pittsburgh compound B: cognitive decline associated with Abeta deposition

Abstract

Objective: To examine the relation of amyloid-beta peptide (Abeta) levels in the cerebral cortex with structural brain integrity and cognitive performance in cognitively healthy older people.

Design: Longitudinal study from May 22, 1985, through October 15, 2008.

Setting: Washington University Alzheimer Disease Research Center.

Participants: A total of 135 individuals aged 65 to 88 years with a Clinical Dementia Rating of 0.

Main outcome measures: The relations between mean cortical carbon 11 ((11)C)-labeled Pittsburgh compound B (PiB) binding potential values, proportional to the density of fibrillar Abeta binding sites in the brain, concurrent regional brain volumes as assessed by magnetic resonance imaging, and both concurrent and longitudinal cognitive performance in multiple domains.

Results: Elevated cerebral Abeta levels, in some cases comparable to those seen in individuals with Alzheimer disease, were observed in 29 participants, who also had smaller regional volumes in the hippocampus, temporal neocortex, anterior cingulate, and posterior cingulate. Concurrent cognitive performance was unrelated to Abeta levels but was related to regional brain volumes with the exception of the caudate. Longitudinal cognitive decline in episodic and working memory and visuospatial ability was associated with elevated Abeta levels and decreased hippocampal volume.

Conclusion: The in vivo measure of cerebral amyloidosis known as [(11)C]PiB is associated with cross-sectional regionally specific brain atrophy and longitudinal cognitive decline in multiple cognitive domains that occur before the clinical diagnosis of Alzheimer disease. These findings contribute to the understanding of the cognitive and structural consequences of Abeta levels in cognitively healthy older adults.

Figure 1

Bar graphs depicting mean regional volumes in the amyloid positive and negative groups. Error bars are SEM.

Figure 2

Longitudinal course of participants with high amyloid values (MCBP ≥ .20) and at least four cognitive assessments. Zero on the time axis is time of imaging.