Dataset Information

Vascular risk and A? interact to reduce cortical thickness in AD vulnerable brain regions.

ABSTRACT:

Objective

The objective of this study was to define whether vascular risk factors interact with ?-amyloid (A?) in producing changes in brain structure that could underlie the increased risk of Alzheimer disease (AD).

Methods

Sixty-six cognitively normal and mildly impaired older individuals with a wide range of vascular risk factors were included in this study. The presence of A? was assessed using [(11)C]Pittsburgh compound B-PET imaging, and cortical thickness was measured using 3-tesla MRI. Vascular risk was measured with the Framingham Coronary Risk Profile Index.

Results

Individuals with high levels of vascular risk factors have thinner frontotemporal cortex independent of A?. These frontotemporal regions are also affected in individuals with A? deposition, but the latter show additional thinning in parietal cortices. A? and vascular risk were found to interact in posterior (especially in parietal) brain regions, where A? has its greatest effect. In this way, the negative effect of A? in posterior regions is increased by the presence of vascular risk.

Conclusion

A? and vascular risk interact to enhance cortical thinning in posterior brain regions that are particularly vulnerable to AD. These findings give insight concerning the mechanisms whereby vascular risk increases the likelihood of developing AD and supports the therapeutic intervention of controlling vascular risk for the prevention of AD.

SUBMITTER: Villeneuve S

PROVIDER: S-EPMC4114172 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Vascular risk and Aβ interact to reduce cortical thickness in AD vulnerable brain regions.

Villeneuve Sylvia S Reed Bruce R BR Madison Cindee M CM Wirth Miranka M Marchant Natalie L NL Kriger Stephen S Mack Wendy J WJ Sanossian Nerses N DeCarli Charles C Chui Helena C HC Weiner Michael W MW Jagust William J WJ

Neurology 20140606 1

<h4>Objective</h4>The objective of this study was to define whether vascular risk factors interact with β-amyloid (Aβ) in producing changes in brain structure that could underlie the increased risk of Alzheimer disease (AD).<h4>Methods</h4>Sixty-six cognitively normal and mildly impaired older individuals with a wide range of vascular risk factors were included in this study. The presence of Aβ was assessed using [(11)C]Pittsburgh compound B-PET imaging, and cortical thickness was measured using ...[more]

PMID: 24907234

Similar Datasets

Project description:ObjectiveTo examine the cross-sectional associations between regional tau, β-amyloid (Aβ), and cortical thickness and neuropsychological function across the preclinical and clinical spectrum of Alzheimer disease (AD).MethodsWe included 106 participants from the Swedish Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study, of whom 33 had preclinical AD (Aβ-positive cognitively normal individuals), 25 had prodromal AD (Aβ-positive mild cognitive impairment), and 48 had probable AD dementia. All underwent [18F]flortaucipir (tau) and structural MRI (cortical thickness), and 88 of 106 underwent [18F]flutemetamol (Aβ) PET. Linear regression models adjusted for age, sex, and education were performed to examine associations between 7 regions of interest and 7 neuropsychological tests for all 3 imaging modalities.ResultsIn preclinical AD, [18F]flortaucipir, but not [18F]flutemetamol or cortical thickness, was associated with decreased global cognition, memory, and processing speed (range standardized β = 0.35-0.52, p < 0.05 uncorrected for multiple comparisons). In the combined prodromal AD and AD dementia group, both increased [18F]flortaucipir uptake and reduced cortical thickness were associated with worse performance on a variety of neuropsychological tests (most regions of interest survived correction for multiple comparisons at p < 0.05), while increased [18F]flutemetamol uptake was specifically associated with lower scores on a delayed recall memory task (p < 0.05 uncorrected for multiple comparisons). The strongest effects for both [18F]flortaucipir and cortical thickness on cognition were found in the lateral and medial parietal cortex and lateral temporal cortex. The effect of [18F]flutemetamol on cognition was generally weaker and less region specific.ConclusionOur findings suggest that tau PET is more sensitive than Aβ PET and measures of cortical thickness for detecting early cognitive changes in preclinical AD. Furthermore, both [18F]flortaucipir PET and cortical thickness show strong cognitive correlates at the clinical stages of AD.

Project description:Introduction: Memory impairment is one of the most commonly reported effects of cannabis use, especially among those who initiate use earlier, perhaps due to the effects of delta-9- tetrahydrocannabinol on cannabinoid (CB1) receptors in the brain. Studies have increasingly investigated whether cannabis use is associated with impairments in verbal memory, and with alterations in brain structures underlying verbal memory. The uncinate fasciculus (UF), a long-range white matter tract, connects regions with densely localized CB1 receptors that are important in verbal memory. This study investigated the impact of cannabis use on UF structures and its association with memory performance in young adult cannabis users (CU) and non-using controls (CON). Materials and Methods: Nineteen CU and 22 CON completed a verbal memory task and a neuroimaging protocol, in which diffusion tensor imaging and structural scans were collected. We compared memory performance, diffusion and tractography measures of the UF, and cortical thickness of regions connected by the UF, between CU and CON. In regions showing a significant group effect, we also examined associations between verbal memory performance, cortical thickness, and age of onset of cannabis use. Results: Compared to non-users, CU had worse memory performance, decreased fiber bundle length in the UF, and decreased cortical thickness of brain regions along the UF such as the entorhinal cortex and fusiform gyrus. Verbal memory performance was significantly associated with age of onset of cannabis use, indicating that those who initiated cannabis use at an earlier age performed worse. Cortical thickness of the entorhinal cortex was significantly correlated with age of first use and memory performance. Conclusion: This study provides evidence that cannabis use, especially when initiated at a young age, may be associated with worse verbal memory and altered neural development along the UF. Reductions in cortical thickness in regions implicated in memory processes may underlie weaknesses in verbal memory performance.