Alzheimer's Disease Neurodegenerative Biomarkers Are Associated with Decreased Cognitive Function but Not beta-Amyloid in Cognitively Normal Older Individuals

作者：Wirth Miranka^*; Madison Cindee M; Rabinovici Gil D; Oh Hwamee; Landau Susan M; Jagust William J

来源：Journal of Neuroscience, 2013, 33(13): 5553-5563.

DOI：10.1523/JNEUROSCI.4409-12.2013

beta-Amyloid (A beta) plaque deposition and neurodegeneration within temporoparietal and hippocampal regions may indicate increased risk of Alzheimer's disease (AD). This study examined relationships between AD biomarkers of A beta and neurodegeneration as well as cognitive performance in cognitively normal older individuals. A beta burden was quantified in 72 normal older human subjects from the Berkeley Aging Cohort (BAC) using [C-11] Pittsburgh compound B (PIB) positron emission tomography. In the same individuals, we measured hippocampal volume, as well as glucose metabolism and cortical thickness, which were extracted from a template of cortical AD-affected regions. The three functional and structural biomarkers were merged into a highly AD-sensitive multimodality biomarker reflecting neural integrity. In the normal older individuals, there was no association between elevated PIB uptake and either the single-modality or the multimodality neurodegenerative biomarkers. Lower neural integrity within the AD-affected regions and a control area (the visual cortex) was related to lower scores on memory and executive function tests; the same association was not found with PIB retention. The relationship between cognition and the multimodality AD biomarker was stronger in individuals with the highest PIB uptake. The findings indicate that neurodegeneration occurs within AD regions regardless of A beta deposition and accounts for worse cognition in cognitively normal older people. The impact of neural integrity on cognitive functions is, however, enhanced in the presence of high A beta burden for brain regions that are most affected in AD.

• 出版日期2013-3-27