White-Matter Hyperintensities and Lacunar Infarcts Are Associated with an Increased Risk of Alzheimer's Disease in the Elderly in China

Background: Frailty, one of serious global health problems in the elderly, is a growing concern in patients with Alzheimer’s disease (AD) because of its high prevalence in AD and its impact on the prognosis. Objective: To investigate the quantitative association between white matter hyperintensities (WMH) and frailty in AD. Methods: A total of 144 outpatients were included. All subjects were evaluated by using Korean version of the CERAD assessment battery and diagnosed very mild to moderate AD. WMH volume was calculated using automated segmentation analysis from the 3D MRI image and further partitioned according to the distance from the ventricular surface. Using the Korean Frailty Index, prefrailty was defined by the scores of 3 and 4 and frailty by the score of 5 and higher. Results: In total, 23.6%were frailty, 32.6%were pre-frailty, and 43.8%were classified as a robust group. The frailty group had higher WMH volume compared to the robust group (p = 0.02), and these trends remained significant after linear regression analyses. According to the subclassification of WMH, using the robust group as a reference, total WMH (OR = 6.297, p = 0.013, 95%CI = 1.463–27.114), juxtaventricular WMH (OR = 12.955, p = 0.014, 95%CI = 1.687–99.509), and periventricular WMH (OR = 3.382, p = 0.025, 95%CI = 1.163–9.8531) volumes were associated with frailty, but deep WMH volume was not. Conclusions: A quarter of patients with very mild to moderate AD is suffering from frailty. Our study provides the evidence of a cross-sectional relationship between WMH volume and frailty, and there is a difference in the association between the subclassification of WMH volume and frailty.

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P3-130: Effects of white matter hyperintensities on the volumes of right and left hippocampus in patients with Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2012.05.1350 ◽

2012 ◽

Vol 8 (4S_Part_14) ◽

pp. P497-P498

Author(s):

Jae-Won Jang ◽

Young Chul Youn ◽

Ko-woon Kim

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

White Matter Hyperintensities ◽

Left Hippocampus

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Topographic patterns of white matter hyperintensities are associated with multimodal neuroimaging biomarkers of Alzheimer’s disease

Alzheimer s Research & Therapy ◽

10.1186/s13195-020-00759-3 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Malo Gaubert ◽

Catharina Lange ◽

Antoine Garnier-Crussard ◽

Theresa Köbe ◽

Salma Bougacha ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Glucose Metabolism ◽

Corpus Callosum ◽

Gray Matter ◽

Fdg Pet ◽

White Matter Hyperintensities ◽

Gray Matter Volume ◽

Matter Volume

Abstract Background White matter hyperintensities (WMH) are frequently found in Alzheimer’s disease (AD). Commonly considered as a marker of cerebrovascular disease, regional WMH may be related to pathological hallmarks of AD, including beta-amyloid (Aβ) plaques and neurodegeneration. The aim of this study was to examine the regional distribution of WMH associated with Aβ burden, glucose hypometabolism, and gray matter volume reduction. Methods In a total of 155 participants (IMAP+ cohort) across the cognitive continuum from normal cognition to AD dementia, FLAIR MRI, AV45-PET, FDG-PET, and T1 MRI were acquired. WMH were automatically segmented from FLAIR images. Mean levels of neocortical Aβ deposition (AV45-PET), temporo-parietal glucose metabolism (FDG-PET), and medial-temporal gray matter volume (GMV) were extracted from processed images using established AD meta-signature templates. Associations between AD brain biomarkers and WMH, as assessed in region-of-interest and voxel-wise, were examined, adjusting for age, sex, education, and systolic blood pressure. Results There were no significant associations between global Aβ burden and region-specific WMH. Voxel-wise WMH in the splenium of the corpus callosum correlated with greater Aβ deposition at a more liberal threshold. Region- and voxel-based WMH in the posterior corpus callosum, along with parietal, occipital, and frontal areas, were associated with lower temporo-parietal glucose metabolism. Similarly, lower medial-temporal GMV correlated with WMH in the posterior corpus callosum in addition to parietal, occipital, and fontal areas. Conclusions This study demonstrates that local white matter damage is correlated with multimodal brain biomarkers of AD. Our results highlight modality-specific topographic patterns of WMH, which converged in the posterior white matter. Overall, these cross-sectional findings corroborate associations of regional WMH with AD-typical Aß deposition and neurodegeneration.

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Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-β in Cognitively Normal Individuals

Journal of Alzheimer s Disease ◽

10.3233/jad-210333 ◽

2021 ◽

pp. 1-11

Author(s):

Fennie Choy Chin Wong ◽

Seyed Ehsan Saffari ◽

Chathuri Yatawara ◽

Kok Pin Ng ◽

Nagaendran Kandiah ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Executive Function ◽

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Amyloid Β ◽

Intracranial Volume ◽

Linear Regression Models ◽

Cognitively Normal

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated. Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined. Methods: This study included 72 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function. Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). Conclusion: BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer’s disease.

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Genetic Variability in Molecular Pathways Implicated in Alzheimer's Disease: A Comprehensive Review

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.646901 ◽

2021 ◽

Vol 13 ◽

Author(s):

David Vogrinc ◽

Katja Goričar ◽

Vita Dolžan

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Age Of Onset ◽

Association Studies ◽

The Elderly ◽

Gene Clustering ◽

Molecular Pathways ◽

Genome Wide Association Studies ◽

Cellular Processes ◽

Increased Risk

Alzheimer's disease (AD) is a complex neurodegenerative disease, affecting a significant part of the population. The majority of AD cases occur in the elderly with a typical age of onset of the disease above 65 years. AD presents a major burden for the healthcare system and since population is rapidly aging, the burden of the disease will increase in the future. However, no effective drug treatment for a full-blown disease has been developed to date. The genetic background of AD is extensively studied; numerous genome-wide association studies (GWAS) identified significant genes associated with increased risk of AD development. This review summarizes more than 100 risk loci. Many of them may serve as biomarkers of AD progression, even in the preclinical stage of the disease. Furthermore, we used GWAS data to identify key pathways of AD pathogenesis: cellular processes, metabolic processes, biological regulation, localization, transport, regulation of cellular processes, and neurological system processes. Gene clustering into molecular pathways can provide background for identification of novel molecular targets and may support the development of tailored and personalized treatment of AD.

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