Cardiorespiratory fitness and preserved medial temporal lobe volume in Alzheimer's Disease

This is not the final published version.Exercise and cardiorespiratory (CR) fitness may moderate age-related regional brain changes in nondemented older adults (ND). The relationship of fitness to Alzheimer's disease (AD) related brain change is understudied, particularly in the hippocampus which is disproportionately affected in early AD. The role of apolipoprotein E4 (apoE4) genotype in modulating this relationship is also unknown. Nondemented (n=56) and early-stage AD subjects (n=61) over age 65 had MRI and CR fitness assessments. Voxel-based morphometry (VBM) techniques were utilized to identify AD-related atrophy. We analyzed the relationship of CR fitness with white and gray matter within groups, assessed fitness-related brain volume change in areas most affected by AD-related atrophy, and then analyzed differential fitness-brain relationships between apoE4 carriers. Atrophy was present in the medial temporal, temporal, and parietal cortices in subjects with mild AD. There was a significant positive correlation of CR fitness with parietal and medial temporal volume in AD subjects. ND subjects did not have a significant relationship between brain volume and CR fitness in the global or SVC analyses. There was not a significant interaction for fitness × apoE4 genotype in either group. In early-stage AD, cardiorespiratory fitness is associated with regional brain volumes in the medial temporal and parietal cortices suggesting that maintaining cardiorespiratory fitness may modify AD-related brain atrophy

Body Composition in Early Alzheimer's Disease

Background: Alzheimer's disease (AD) is associated with unintended weight loss. We examined body composition in early AD and nondemented aging and its relation to brain volume and cognition. Methods: Brain magnetic resonance imaging (MRI) and neuropsychological testing were performed on nondemented (CDR 0, n=70) and early-stage AD (CDR 0.5 or 1, n=70) subjects. Dual energy x-ray absorptiometry (DEXA) determined whole-body fat mass and lean mass. Body mass index (BMI) was determined from height and weight. Linear regression analyses controlling for age and sex assessed the relationship between body composition, cognition, and brain volume. Results: Lean mass was reduced in early AD compared to nondemented controls (F=7.73, p=0.006) after controlling for sex. Lean mass was associated with whole-brain volume (beta=0.20, p<0.001) and white matter volume (beta=0.19, p<0.001) when controlling for age and sex. Lean mass was also associated with global cognitive performance (beta=0.12, p=0.007) when controlling for age and sex. Total body fat and percent body fat were not different across groups or related to cognition and brain volume. Conclusion: Loss of lean mass is accelerated in AD and associated with brain atrophy. AD and sarcopenia may share common underlying mechanisms or sarcopenia may be a direct or indirect consequence of AD pathophysiology

Mild cognitive impairment: historical development and summary of research

This review article broadly traces the historical development, diagnostic criteria, clinical and neuropathological characteristics, and treatment strategies related to mild cognitive impairment (MCI), The concept of MCI is considered in the context of other terms that have been developed to characterize the elderly with varying degrees of cognitive impairment Criteria based on clinical global scale ratings, cognitive test performance, and performance on other domains of functioning are discussed. Approaches employing clinical, neuropsychological, neuroimaging, biological, and molecular genetic methodology used in the validation of MCI are considered, including results from cross-sectional, longitudinal, and postmortem investigations. Results of recent drug treatment studies of MCI and related methodological issues are also addressed

Frontal White Matter Integrity in Adults with Down Syndrome with and without Dementia

Adults with Down syndrome (DS) are at high risk for developing Alzheimer\u27s disease after the age of 40 years. To detect white matter (WM) changes in the brain linked to dementia, fractional anisotropy (FA) from diffusion tensor imaging was used. We hypothesized that adults with DS without dementia (DS n = 10), DS with dementia (DSAD n = 10) and age matched non-DS subjects (CTL n = 10) would show differential levels of FA and an association with scores from the Brief Praxis Test and the Severe Impairment Battery. WM integrity differences in DS compared with CTL were found predominantly in the frontal lobes. Across all DS adults, poorer Brief Praxis Test performance correlated with reduced FA in the corpus callosum as well as several association tracts, primarily within frontoparietal regions. Our results demonstrate significantly lower WM integrity in DS compared with controls, particularly in the frontal tracts. DS-related WM integrity reductions in a number of tracts were associated with poorer cognition. These preliminary results suggest that late myelinating frontal pathways may be vulnerable to aging in DS

Age Related Changes in Cerebrovascular Reactivity and Its Relationship to Global Brain Structure

ACKNOWLEDGMENTS This study was funded by Alzheimer’s Research UK (ARUK) and the Aberdeen Biomedical Imaging Centre, University of Aberdeen. GDW, ADM and CS are part of the SINASPE collaboration (Scottish Imaging Network - A Platform for Scientific Excellence www.SINAPSE.ac.uk). The authors thank Gordon Buchan, Baljit Jagpal, Nichola Crouch, Beverly Maclennan and Katrina Klaasen for their help with running the experiment and Dawn Younie and Teresa Morris for their help with recruitment and scheduling. We also thank the residents of Aberdeen and Aberdeenshire, and further afield, for their generous participation.Peer reviewedPublisher PD

Diagnostic Utility of Cerebral White Matter Integrity in Early Alzheimer's Disease

This is an Accepted Manuscript of an article published by Taylor & Francis in International Journal of Neuroscience on August 2010, available online: http://www.tandfonline.com/10.3109/00207454.2010.494788.We compared white matter integrity with brain atrophy in healthy controls and participants with very mild dementia (Clinical Dementia Rating 0 vs. 0.5) from the Brain Aging Project, a longitudinal study of aging and memory at the University of Kansas Medical Center. Structural magnetic resonance imaging and diffusion tensor imaging (DTI) including fractional anisotropy and mean diffusivity were performed on 27 patients with very mild dementia (Clinical Dementia Rating = 0.5) of the Alzheimer's type (DAT), and 32 cognitively normal subjects. Patient groups were compared across 6 volumetric measures and 14 DTI regions of interest. Very mildly demented patients showed expected disease-related patterns of brain atrophy with reductions in whole-brain and hippocampal volumes most prominent. DTI indices of white matter integrity were mixed. Right parahippocampus showed significant but small disease-related reductions in fractional anisotropy. Right parahippocampus and left internal capsule showed greater mean diffusivity in early DAT compared with controls. A series of discriminant analyses demonstrated that gray matter atrophy was a significantly better predictor of dementia status than were DTI indices. Brain atrophy was most strongly related to very mild DAT. Modest disease-related white matter anomalies were present in temporal cortex, and deep white matter had limited discriminatory diagnostic power, probably because of the very mild stage of disease in these participants

Peripheral apoE isoform levels in cognitively normal APOE ε3/ε4 individuals are associated with regional gray matter volume and cerebral glucose metabolism

abstract: Background Carriers of the APOE ε4 allele are at increased risk of developing Alzheimer’s disease (AD), and have been shown to have reduced cerebral metabolic rate of glucose (CMRgl) in the same brain areas frequently affected in AD. These individuals also exhibit reduced plasma levels of apolipoprotein E (apoE) attributed to a specific decrease in the apoE4 isoform as determined by quantification of individual apoE isoforms in APOE ε4 heterozygotes. Whether low plasma apoE levels are associated with structural and functional brain measurements and cognitive performance remains to be investigated. Methods Using quantitative mass spectrometry we quantified the plasma levels of total apoE and the individual apoE3 and apoE4 isoforms in 128 cognitively normal APOE ε3/ε4 individuals included in the Arizona APOE cohort. All included individuals had undergone extensive neuropsychological testing and 25 had in addition undergone FDG-PET and MRI to determine CMRgl and regional gray matter volume (GMV). Results Our results demonstrated higher apoE4 levels in females versus males and an age-dependent increase in the apoE3 isoform levels in females only. Importantly, a higher relative ratio of apoE4 over apoE3 was associated with GMV loss in the right posterior cingulate and with reduced CMRgl bilaterally in the anterior cingulate and in the right hippocampal area. Additional exploratory analysis revealed several negative associations between total plasma apoE, individual apoE isoform levels, GMV and CMRgl predominantly in the frontal, occipital and temporal areas. Finally, our results indicated only weak associations between apoE plasma levels and cognitive performance which further appear to be affected by sex. Conclusions Our study proposes a sex-dependent and age-dependent variation in plasma apoE isoform levels and concludes that peripheral apoE levels are associated with GMV, CMRgl and possibly cognitive performance in cognitively healthy individuals with a genetic predisposition to AD.The electronic version of this article is the complete one and can be found online at: https://alzres.biomedcentral.com/articles/10.1186/s13195-016-0231-