Association of moderate alcohol intake with in vivo amyloid-beta deposition in human brain: A cross-sectional study.
Kim Jee Wook,Byun Min Soo,Yi Dahyun,Lee Jun Ho,Ko Kang,Jeon So Yeon,Sohn Bo Kyung,Lee Jun-Young,Kim Yu Kyeong,Shin Seong A,Sohn Chul-Ho,Lee Dong Young,
BACKGROUND:An emerging body of literature has indicated that moderate alcohol intake may be protective against Alzheimer disease (AD) dementia. However, little information is available regarding whether moderate alcohol intake is related to reductions in amyloid-beta (Aβ) deposition, or is protective via amyloid-independent mechanisms in the living human brain. Here we examined the associations of moderate alcohol intake with in vivo AD pathologies, including cerebral Aβ deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMHs) in the living human brain. METHODS AND FINDINGS:The present study was part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study that started in 2014. As of November 2016, 414 community-dwelling individuals with neither dementia nor alcohol-related disorders (280 cognitively normal [CN] individuals and 134 individuals with mild cognitive impairment [MCI]) between 56 and 90 years of age (mean age 70.9 years ± standard deviation 7.8; male, n [%] = 180 [43.5]) were recruited from 4 sites (i.e., 2 university hospitals and 2 public centers for dementia prevention and management) around Seoul, South Korea. All the participants underwent comprehensive clinical assessments comprising lifetime and current histories of alcohol intake and multimodal brain imaging, including [11C] Pittsburgh compound B positron emission tomography (PET), [18F] fluorodeoxyglucose (FDG) PET, and magnetic resonance imaging (MRI) scans. Lifetime and current alcohol intake were categorized as follows: no drinking, <1 standard drink (SD)/week, 1-13 SDs/week, and 14+ SDs/week. A moderate lifetime alcohol intake (1-13 SDs/week) was significantly associated with a lower Aβ positivity rate compared to the no drinking group, even after controlling for potential confounders (odds ratio 0.341, 95% confidence interval 0.163-0.714, p = 0.004). In contrast, current alcohol intake was not associated with amyloid deposition. Additionally, alcohol intake was not related to neurodegeneration of AD-signature regions or cerebral WMH volume. The present study had some limitations in that it had a cross-sectional design and depended on retrospective recall for alcohol drinking history. CONCLUSIONS:In this study, we observed in middle- and old-aged individuals with neither dementia nor alcohol-related disorders that moderate lifetime alcohol intake was associated with lower cerebral Aβ deposition compared to a lifetime history of not drinking. Moderate lifetime alcohol intake may have a beneficial influence on AD by reducing pathological amyloid deposition rather than amyloid-independent neurodegeneration or cerebrovascular injury.
Associations of equol-producing status with white matter lesion and amyloid-β deposition in cognitively normal elderly Japanese.
Sekikawa Akira,Higashiyama Aya,Lopresti Brian J,Ihara Masafumi,Aizenstein Howard,Watanabe Makoto,Chang Yuefang,Kakuta Chikage,Yu Zheming,Mathis Chester,Kokubo Yoshihioro,Klunk William,Lopez Oscar L,Kuller Lewis H,Miyamoto Yoshihiro,Cui Chendi
Alzheimer's & dementia (New York, N. Y.)
Introduction:Equol, a metabolite of a soy isoflavone transformed by the gut microbiome, is anti-oxidant and anti-amyloidogenic. We assessed the associations of equol with white matter lesion normalized to total brain volume (WML%) and amyloid beta (Aβ) deposition. Methods:From 2016 to 2018, 91 cognitively normal elderly Japanese aged 75 to 89 underwent brain magnetic resonance imaging and positron emission tomography using C-Pittsburgh compound-B. Serum equol was measured using stored samples from 2008 to 2012. Equol producers were defined as individuals with serum levels >0. Producers were further divided into high (> the median) and low (≤ the median) producers. Results:The median (interquartile range) WML% was 1.10 (0.59 to 1.61); 24.2% were Aβ positive, and 51% were equol producers. Equol-producing status (non-producers, low and high) was significantly inversely associated with WML%: 1.19, 0.89, and 0.58, respectively (trend < .01). Equol-producing status was not associated with Aβ status. Discussion:A randomized-controlled trial of equol targeting WML volume is warranted.
Amyloid β influences the relationship between cortical thickness and vascular load.
Parker Thomas D,Cash David M,Lane Christopher A,Lu Kirsty,Malone Ian B,Nicholas Jennifer M,James Sarah-Naomi,Keshavan Ashvini,Murray-Smith Heidi,Wong Andrew,Buchanan Sarah M,Keuss Sarah E,Sudre Carole H,Thomas David L,Crutch Sebastian J,Fox Nick C,Richards Marcus,Schott Jonathan M
Alzheimer's & dementia (Amsterdam, Netherlands)
Introduction:Cortical thickness has been proposed as a biomarker of Alzheimer's disease (AD)- related neurodegeneration, but the nature of its relationship with amyloid beta (Aβ) deposition and white matter hyperintensity volume (WMHV) in cognitively normal adults is unclear. Methods:We investigated the influences of Aβ status (negative/positive) and WMHV on cortical thickness in 408 cognitively normal adults aged 69.2 to 71.9 years who underwent F-Florbetapir positron emission tomography (PET) and structural magnetic resonance imaging (MRI). Two previously defined Alzheimer's disease (AD) cortical signature regions and the major cortical lobes were selected as regions of interest (ROIs) for cortical thickness. Results:Higher WMHV, but not Aβ status, predicted lower cortical thickness across all participants, in all ROIs. Conversely, when Aβ-positive participants were considered alone, higher WMHV predicted higher cortical thickness in a temporal AD-signature region. Discussion:WMHV may differentially influence cortical thickness depending on the presence or absence of Aβ, potentially reflecting different pathological mechanisms.
Age-dependent amyloid deposition is associated with white matter alterations in cognitively normal adults during the adult life span.
Caballero Miguel Á Araque,Song Zhuang,Rubinski Anna,Duering Marco,Dichgans Martin,Park Denise C,Ewers Michael
Alzheimer's & dementia : the journal of the Alzheimer's Association
INTRODUCTION:Both beta-amyloid (Ab) deposition and decline in white matter integrity, are brain alterations observed in Alzheimer's disease (AD) and start to occur by the fourth and fifth decades. However, the association between both brain alterations in asymptomatic subjects is unclear. METHODS:Amyloid positron emission tomography (PET) and diffusion tensor imaging (DTI) were obtained in 282 cognitively normal subjects (age 30-89 years). We assessed the interaction of age by abnormal amyloid PET status (Florbetapir F-18 PET >1.2 standard uptake value ratio [SUVR]) on regional mean diffusivity (MD) and global white matter hyperintensity (WMH) volume, controlled for sex, education, and hypertension. RESULTS:Subjects with abnormal amyloid PET (n = 87) showed stronger age-related increase in global WMH and regional MD, particularly within the posterior parietal regions of the white matter. DISCUSSION:Sporadic Aβ deposition is associated with white matter alterations in AD predilection areas in an age-dependent manner in cognitively normal individuals.
Diffusion MRI biomarkers of white matter microstructure vary nonmonotonically with increasing cerebral amyloid deposition.
Dong Jian W,Jelescu Ileana O,Ades-Aron Benjamin,Novikov Dmitry S,Friedman Kent,Babb James S,Osorio Ricardo S,Galvin James E,Shepherd Timothy M,Fieremans Els
Neurobiology of aging
Beta amyloid (Aβ) accumulation is the earliest pathological marker of Alzheimer's disease (AD), but early AD pathology also affects white matter (WM) integrity. We performed a cross-sectional study including 44 subjects (23 healthy controls and 21 mild cognitive impairment or early AD patients) who underwent simultaneous PET-MR using 18F-Florbetapir, and were categorized into 3 groups based on Aβ burden: Aβ- [mean mSUVr ≤1.00], Aβi [1.00 < mSUVr <1.17], Aβ+ [mSUVr ≥1.17]. Intergroup comparisons of diffusion MRI metrics revealed significant differences across multiple WM tracts. Aβi group displayed more restricted diffusion (higher fractional anisotropy, radial kurtosis, axonal water fraction, and lower radial diffusivity) than both Aβ- and Aβ+ groups. This nonmonotonic trend was confirmed by significant continuous correlations between mSUVr and diffusion metrics going in opposite direction for 2 cohorts: pooled Aβ-/Aβi and pooled Aβi/Aβ+. The transient period of increased diffusion restriction may be due to inflammation that accompanies rising Aβ burden. In the later stages of Aβ accumulation, neurodegeneration is the predominant factor affecting diffusion.