Cross-sectional and longitudinal analysis of the relationship between aβ deposition, cortical thickness, and memory in cognitively unimpaired individuals and in alzheimer disease

Vincent Doré*, Victor L. Villemagne, Pierrick Bourgeat, Jurgen Fripp, Oscar Acosta, Gael Chetélat, Luping Zhou, Ralph Martins, Kathryn A. Ellis, Colin L. Masters, David Ames, Oliver Salvado, Christopher C. Rowe

*Corresponding author for this work

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Importance β-amyloid (Aβ) deposition is one of the hallmarks of Alzheimer disease. Aβ deposition accelerates gray matter atrophy at early stages of the disease even before objective cognitive impairment is manifested. Identification of at-risk individuals at the presymptomatic stage has become a major research interest because it will allow early therapeutic interventions before irreversible synaptic and neuronal loss occur.We aimed to further characterize the cross-sectional and longitudinal relationship between Aβ deposition, gray matter atrophy, and cognitive impairment. OBJECTIVE To investigate the topographical relationship of Aβ deposition, gray matter atrophy, and memory impairment in asymptomatic individuals with Alzheimer disease pathology as assessed by Pittsburgh compound B positron emission tomography (PiB-PET). DESIGN Regional analysis was performed on the cortical surface to relate cortical thickness to PiB retention and episodic memory. SETTING The Australian Imaging, Biomarkers, and Lifestyle Study of Aging, Austin Hospital, Melbourne, Australia. PARTICIPANTS Ninety-three healthy elderly control subjects (NCs) and 40 patients with Alzheimer disease from the Australian Imaging, Biomarkers, and Lifestyle Study of Aging cohort. INTERVENTION Participants underwent neuropsychological evaluation as well as magnetic resonance imaging and PiB-PET scans. Fifty-four NCs underwent repeated scans and neuropsychological evaluation 18 and 36 months later. MAIN OUTCOMES AND MEASURES Correlations between cortical thickness, PiB retention, and episodic memory. RESULTS There was a significant reduction in cortical thickness in the precuneus and hippocampus associated with episodic memory impairment in the NC PiB-positive (NC+) group when compared with the NC- group. Cortical thickness was also correlated negatively with neocortical PiB in the NC+ group. Longitudinal analysis showed a faster rate of gray matter (GM) atrophy in the temporal lobe and the hippocampi of the NC+ group. Over time, GM atrophy became more extensive in the NC+ group, especially in the temporal lobe. CONCLUSIONS AND RELEVANCE In asymptomatic individuals, Aβ deposition is associated with GM atrophy and memory impairment. The earliest signs of GM atrophy were detected in the hippocampus and the posterior cingulate and precuneus regions, and with disease progression, atrophy became more extensive in the temporal lobes. These findings support the notion that Aβ deposition is not a benign process and that interventions with anti-Aβ therapy at these early stages have a higher chance to be effective.

Original languageEnglish
Pages (from-to)903-911
Number of pages9
JournalJAMA Neurology
Volume70
Issue number7
DOIs
Publication statusPublished - 2013
Externally publishedYes

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