Association of gray matter atrophy with age, ß-amyloid, and cognition in aging.

Both cognitive aging and ß-amyloid (Aß) deposition, a pathological hallmark of Alzheimer's disease, are associated with structural and cognitive changes in cognitively normal older people. To examine independent effects of age and Aß deposition on cognition and brain structure in aging, 83 cognitively normal older adults underwent structural magnetic resonance imaging scans and neuropsychological tests and were classified as negative (PIB-) or positive (PIB+) for Aß deposition using the radiotracer Pittsburgh compound B (PIB). Weighted composite discriminant scores represented subjects' cognition. Older adults showed age-related gray matter (GM) atrophy across the whole brain regardless of Aß deposition. Amyloid burden within PIB+ subjects, however, was associated with GM atrophy in the frontal, parietal, and temporal cortices. Associations between cognition and volume in PIB- subjects were primarily seen throughout frontal regions and the striatum, while, in PIB+ subjects, these associations were seen in orbital-frontal and hippocampal regions. Furthermore, in PIB- subjects, cognition was related to putaminal volume, but not to hippocampus, while, in PIB+ subjects, cognition was related to hippocampal volume, but not to putamen. These findings highlight differential age and Aß effects on brain structure, indicating effects of age and Aß that operate somewhat independently to affect frontostriatal and medial temporal brain systems.

The effect of amyloid ß on cognitive decline is modulated by neural integrity in cognitively normal elderly.

OBJECTIVE: Alzheimer's disease (AD) pathology of amyloid ß (Aß) accumulation and neurodegeneration may be relevant to preclinical cognitive decline. The objective of this study was to relate AD-sensitive biomarkers of Aß and neurodegeneration and their interaction to longitudinal cognitive change in cognitively normal elderly. METHODS: Thirty-eight older people completed at least three consecutive neuropsychological examinations. Using positron emission tomography (PET), Aß plaque burden was measured with [(11)C]Pittsburgh compound B (PiB). PiB retention was dichotomized into a positive (n = 13) and negative (n = 25) PiB status. Neurodegenerative biomarkers were extracted within AD-vulnerable regions of interest (ROIs)-namely, the hippocampus and temporoparietal cortical areas. Within each ROI, metabolism was quantified with [(18)F] fluorodeoxyglucose (FDG) PET, and the gray matter structure was evaluated using volume (hippocampus) or thickness (cortical regions). ROI-specific functional and structural biomarkers were combined further into cross-modality neurodegenerative composite measures. Using hierarchical regression models, PiB and the neurodegenerative biomarkers were related to cognitive trajectories. RESULTS: PiB positivity was associated with memory and nonmemory worsening. The neurodegenerative biomarkers modified these relationships. Longitudinal cognitive decline was accelerated in those individuals who exhibited both PiB positivity and lower neurodegenerative biomarker scores, although the two measures appeared to be independent. PiB retention interacted predominantly with the cortical neurodegenerative composite for nonmemory change. Memory decline was best explained by the interaction between PiB and the hippocampal neurodegenerative composite, suggesting regional specificity of the neurodegenerative modulations. CONCLUSIONS: Our findings indicate that cognitive trajectories deteriorate at a faster rate in cognitively normal individuals expressing Aß burden and neurodegeneration within specific AD-sensitive regions.

Effects of age and ß-amyloid on cognitive changes in normal elderly people.

Age-related decline is common in multiple cognitive domains. ß-amyloid (Aß) deposition, a pathological hallmark of Alzheimer's disease, is also associated with cognitive changes in many older people. In this study, we examined a wide range of cognitive function in order to differentiate the effect of age and Aß on cognition during aging. Using positron emission tomography (PET) imaging with the radiotracer Pittsburgh Compound B (PIB), we classified normal older subjects as High PIB-Old and Low PIB-Old and applied sequential multivariate analyses (i.e., principal components analysis [PCA] and discriminant analysis) to obtain summary measures of cognitive tests encompassing multiple cognitive domains. Among 5 cognitive components, a significant age effect was observed in component scores of visual memory and executive functions, regardless of the level of Aß. Discriminant scores (weighted scores of the 5 cognitive components) revealed a significant effect of both age and Aß and were further associated with quantitative PIB counts. The results of the current study highlight both effects of age and Aß on cognitive changes in normal elderly.