Dataset Information

Prefrontal Lobe Brain Reserve Capacity with Resistance to Higher Global Amyloid Load and White Matter Hyperintensity Burden in Mild Stage Alzheimer's Disease.

ABSTRACT:

Background

Amyloid deposition and white matter lesions (WMLs) in Alzheimer's disease (AD) are both considered clinically significant while a larger brain volume is thought to provide greater brain reserve (BR) against these pathological effects. This study identified the topography showing BR in patients with mild AD and explored the clinical balances among BR, amyloid, and WMLs burden.

Methods

Thirty patients with AD were enrolled, and AV-45 positron emission tomography was conducted to measure the regional standardized uptake value ratio (SUVr) in 8 cortical volumes-of- interests (VOIs). The quantitative WMLs burden was measured from magnetic resonance imaging while the normalized VOIs volumes represented BR in this study. The cognitive test represented major clinical correlates.

Results

Significant correlations between the prefrontal volume and global (r = 0.470, p = 0.024), but not regional (r = 0.264, p = 0.223) AV-45 SUVr were found. AD patients having larger regional volume in the superior- (r = 0.572, p = 0.004), superior medial- (r = 0.443, p = 0.034), and middle-prefrontal (r = 0.448, p = 0.032) regions had higher global AV-45 SUVr. For global WML loads, the prefrontal (r = -0.458, p = 0.019) and hippocampal volume (r = -0.469, p = 0.016) showed significant correlations while the prefrontal (r = -0.417, p = 0.043) or hippocampal volume (r = -0.422, p = 0.04) also predicted better composite memory scores. There were no interactions between amyloid SUVr and WML loads on the prefrontal volume.

Conclusions

BR of the prefrontal region might modulate the adverse global pathological burden caused by amyloid deposition. While prefrontal volume positively associated with hippocampal volume, WMLs had an adverse impact on the hippocampal volume that predicts memory performance in mild stage AD.

SUBMITTER: Chang YT

PROVIDER: S-EPMC4752238 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Prefrontal Lobe Brain Reserve Capacity with Resistance to Higher Global Amyloid Load and White Matter Hyperintensity Burden in Mild Stage Alzheimer's Disease.

Chang Ya-Ting YT Huang Chi-Wei CW Chen Nai-Ching NC Lin Kun-Ju KJ Huang Shu-Hua SH Chang Yen-Hsiang YH Hsu Shih-Wei SW Chang Wen-Neng WN Lui Chun-Chung CC Hsu Che-Wei CW Chang Chiung-Chih CC

PloS one 20160212 2

<h4>Background</h4>Amyloid deposition and white matter lesions (WMLs) in Alzheimer's disease (AD) are both considered clinically significant while a larger brain volume is thought to provide greater brain reserve (BR) against these pathological effects. This study identified the topography showing BR in patients with mild AD and explored the clinical balances among BR, amyloid, and WMLs burden.<h4>Methods</h4>Thirty patients with AD were enrolled, and AV-45 positron emission tomography was condu ...[more]

PMID: 26872386

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Project description:BackgroundWhite matter hyperintensities (WMHs) are often measured globally, but spatial patterns of WMHs could underlie different risk factors and neuropathological and clinical correlates. We investigated the spatial heterogeneity of WMHs and their association with comorbidities, Alzheimer's disease (AD) risk factors, and cognition.MethodsIn this cross-sectional study, we studied 171 cognitively unimpaired (CU; median age: 65 years, range: 50 to 89) and 51 mildly cognitively impaired (MCI; median age: 72, range: 53 to 89) individuals with available amyloid (18F-flutementamol) PET and FLAIR-weighted images. Comorbidities were assessed using the Cumulative Illness Rating Scale (CIRS). Each participant's white matter was segmented into 38 parcels, and WMH volume was calculated in each parcel. Correlated principal component analysis was applied to the parceled WMH data to determine patterns of WMH covariation. Adjusted and unadjusted linear regression models were used to investigate associations of component scores with comorbidities and AD-related factors. Using multiple linear regression, we tested whether WMH component scores predicted cognitive performance.ResultsPrincipal component analysis identified four WMH components that broadly describe FLAIR signal hyperintensities in posterior, periventricular, and deep white matter regions, as well as basal ganglia and thalamic structures. In CU individuals, hypertension was associated with all patterns except the periventricular component. MCI individuals showed more diverse associations. The posterior and deep components were associated with renal disorders, the periventricular component was associated with increased amyloid, and the subcortical gray matter structures was associated with sleep disorders, endocrine/metabolic disorders, and increased amyloid. In the combined sample (CU + MCI), the main effects of WMH components were not associated with cognition but predicted poorer episodic memory performance in the presence of increased amyloid. No interaction between hypertension and the number of comorbidities on component scores was observed.ConclusionOur study underscores the significance of understanding the regional distribution patterns of WMHs and the valuable insights that risk factors can offer regarding their underlying causes. Moreover, patterns of hyperintensities in periventricular regions and deep gray matter structures may have more pronounced cognitive implications, especially when amyloid pathology is also present.

Project description:Abstract White matter hyperintensities are areas of hyperintense signal on MRI that typically represent cerebrovascular pathology. While focal white matter hyperintensities are common among older individuals, extensive white matter hyperintensities have been found to accelerate the progression of dementia. However, little is currently known about how various socioeconomic, health, lifestyle and environmental factors affect the severity of these lesions, particularly in low- and middle-income countries such as India. We investigated this question using cross-sectional MRI data (n = 126) from a pilot neuroimaging sub-study of an ongoing, nationally representative epidemiological study of late-life cognition in India. As a screening step, we estimated white matter hyperintensity load from fluid-attenuated inversion recovery MRI using a fully automated technique and tested for associations with each factor separately, controlling for age, sex and estimated total intracranial volume in each case. A combined model of white matter hyperintensity load included five factors which were significant after multiple comparisons correction: systolic blood pressure, body mass index, urbanicity status (urban versus rural living), daily chore hours and the frequency of store trips. This model explained an additional 27% of the variance in white matter hyperintensity load (54 versus 27% for the baseline model with only age, sex and estimated total intracranial volume). We accounted for the possibility of reverse causality by additionally controlling for concurrent markers of neurodegeneration and cognitive impairment, with no substantial change in our findings. Overall, our findings suggest that controlling high blood pressure and maintaining both a healthy body mass index and high levels of physical activity may reduce white matter hyperintensity load in older Indian adults, helping to prevent or delay dementia. Aksman et al. investigated which socioeconomic, health and lifestyle factors affect the white matter hyperintensity (WMH) load in older Indians, finding that high blood pressure, high body mass index and low levels of physical activity contribute to WMH load in this population. Graphical Abstract Graphical abstract

Dataset Information

Prefrontal Lobe Brain Reserve Capacity with Resistance to Higher Global Amyloid Load and White Matter Hyperintensity Burden in Mild Stage Alzheimer's Disease.

Background

Methods

Results

Conclusions

Publications

Prefrontal Lobe Brain Reserve Capacity with Resistance to Higher Global Amyloid Load and White Matter Hyperintensity Burden in Mild Stage Alzheimer's Disease.

Similar Datasets

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