Cardiovascular risk factors and future risk of Alzheimer's disease

Alzheimer's disease (AD) is the most common neurodegenerative disorder in elderly people, but there are still no curative options. Senile plaques and neurofibrillary tangles are considered hallmarks of AD, but cerebrovascular pathology is also common. In this review, we summarize findings on cardiovascular disease (CVD) and risk factors in the etiology of AD. Firstly, we discuss the association of clinical CVD (such as stroke and heart disease) and AD. Secondly, we summarize the relation between imaging makers of pre-clinical vascular disease and AD. Lastly, we discuss the association of cardiovascular risk factors and AD. We discuss both established cardiovascular risk factors and emerging putative risk factors, which exert their effect partly via CVD

Reduced DTI-ALPS in H-type hypertension: insights into perivascular space function

Recent studies suggest that glymphatic dysfunction plays a significant role in vascular cognitive impairment (VCI). Both hypertension and hyperhomocysteinemia are independent risk factors for VCI, and their combination is referred to as H-type hypertension (HHT). However, the impact of HHT on glymphatic function remains unclear. This study used the recently popular indirect marker, diffusion tensor imaging along the perivascular space (DTI-ALPS) to assess potential changes in glymphatic function in patients with HHT. We recruited 58 HHT patients and 50 healthy controls without hypertension, collecting clinical, cognitive, biochemical, and diffusion MRI data. Behaviorally, HHT patients scored lower on global cognitive tests compared to controls. DTI-ALPS analysis revealed a bilateral reduction in DTI-ALPS in HHT patients. Correlation analysis showed strong associations between lower DTI-ALPS values, reduced cognitive scores, and elevated homocysteine (Hcy) levels in HHT patients. Mediation analysis further indicated that DTI-ALPS largely mediates the relationship between Hcy levels and cognitive performance. These findings suggest that hypertension and elevated Hcy levels contribute to DTI-ALPS reduction, which may underlie the cognitive decline observed in HHT

Effects of dance therapy on balance, gait and neuro-psychological performances in patients with Parkinson's disease and postural instability

Postural Instability (PI) is a core feature of Parkinson’s Disease (PD) and a major cause of falls and disabilities. Impairment of executive functions has been called as an aggravating factor on motor performances. Dance therapy has been shown effective for improving gait and has been suggested as an alternative rehabilitative method. To evaluate gait performance, spatial-temporal (S-T) gait parameters and cognitive performances in a cohort of patients with PD and PI modifications in balance after a cycle of dance therapy

Confining the Concept of Vascular Depression to Late-Onset Depression: A Meta-Analysis of MRI-Defined Hyperintensity Burden in Major Depressive Disorder and Bipolar Disorder

Background: The vascular depression hypothesis emphasizes the significance of vascular lesions in late-life depression. At present, no meta-analytic model has investigated whether a difference in hyperintensity burden compared to controls between late-life and late-onset depression is evident. By including a substantial number of studies, focusing on a meaningful outcome measure, and considering several moderating and control variables, the present meta-analysis investigates the severity of hyperintensity burden in major depressive disorder (MDD) and bipolar disorder (BD). A major focus of the present meta-analysis refers to the role of age at illness onset. It is analyzed whether late-onset rather than late-life depression characterizes vascular depression.Method: In total, 68 studies were included in the meta-analysis and a multilevel random effects model was calculated using Hedges' g as the effect size measure.Results: The severity of hyperintensity burden was significantly greater in the patient group compared to the control group. This effect was evident regarding the whole patient group (g = 0.229) as well as both depression subgroups, with a significantly greater effect in BD (g = 0.374) compared to MDD (g = 0.189). Hyperintensity burden was more pronounced in late-onset depression than in early-onset depression or late-life depression. A considerable heterogeneity between the included studies was observed, which is reflected by the large variability in effects sizes.Conclusion: In conclusion, the present meta-analysis underscores the association of hyperintensities with MDD and BD. Especially late-onset depression is associated with an increased hyperintensity burden, which is in line with the vascular depression hypothesis. The results suggest that it might be more feasible to confine the concept of vascular depression specifically to late-onset depression as opposed to late-life depression. Further research is needed to understand the causal mechanisms that might underlie the relation between hyperintensity burden and depression

Recent publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing progress toward improved AD clinical trials

INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the over 400 publications using ADNI data during 2014 and 2015. METHODS: We used standard searches to find publications using ADNI data. RESULTS: (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses. Models of prion-like spreading of Aβ pathology along WM tracts predict known patterns of cortical Aβ deposition and declines in glucose metabolism; (7) New AD risk and protective gene loci have been identified using biologically informed approaches; (8) Cognitively normal and mild cognitive impairment (MCI) subjects are heterogeneous and include groups typified not only by "classic" AD pathology but also by normal biomarkers, accelerated decline, and suspected non-Alzheimer's pathology; (9) Selection of subjects at risk of imminent decline on the basis of one or more pathologies improves the power of clinical trials; (10) Sensitivity of cognitive outcome measures to early changes in cognition has been improved and surrogate outcome measures using longitudinal structural magnetic resonance imaging may further reduce clinical trial cost and duration; (11) Advances in machine learning techniques such as neural networks have improved diagnostic and prognostic accuracy especially in challenges involving MCI subjects; and (12) Network connectivity measures and genetic variants show promise in multimodal classification and some classifiers using single modalities are rivaling multimodal classifiers. DISCUSSION: Taken together, these studies fundamentally deepen our understanding of AD progression and its underlying genetic basis, which in turn informs and improves clinical trial desig

The influence of diet and metabolism on hippocampus and hypothalamus connectivity across the lifespan

The high prevalence of unhealthy dietary patterns, obesity, and related brain disorders such as dementia emphasise the importance of research that examines the effect of dietary and metabolic factors on brain health. Using magnetic resonance imaging (MRI) to assess brain grey matter functional connectivity (FC) and volumes, this thesis aimed to examine the relationship between measures of diet and metabolism and the brain over the adult lifespan. First, a systematic review was conducted, to examine the relationship between dietary and metabolic health in relation to a wide range of brain MRI markers. The reviewed evidence suggested that lower dietary and metabolic health quality was related to reduced brain volume and connectivity, especially in the default mode network and the frontal and temporal lobes, although there were contrasting trends for each of these associations. To address the gaps identified by the review, we examined the association between dietary and metabolic health in relation to the hippocampus and hypothalamus FC and volumes in the cross-sectional Human Connectome Project cohort of 400 younger adults and in the longitudinal Whitehall II cohort of 775 midlife-older aged adults. The Whitehall cohort had longitudinal measures of diet/metabolic markers collected every 5 years throughout their midlife (40-70 years old). First, we note that different dietary and metabolic markers have unique patterns of longitudinal trajectories from mid-to-old-age. Our findings supported the hypothesis that better dietary and metabolic health is associated with volumetric and FC differences of the hippocampus and the hypothalamus both in younger and older cohorts. Specifically, dietary and metabolic health was linked to (1) hippocampal FC with the frontal lobe, precentral gyrus, and occipital lobe and (2) hypothalamic FC with the brainstem and the basal forebrain. These findings contribute to a growing understanding of the brain networks associated with dietary and metabolic health. The thesis provides insights into when in life dietary and metabolic health measures are related to brain health. Our findings indicated that in order to promote brain health in older age, some metabolic factors may be better targeted in midlife (e.g., cholesterol, diet, abdominal fat), while other factors should be targeted as early as possible (blood pressure, body composition/BMI). This may have implications for preventative lifestyle interventions to reduce the risk of developing dementia and to maintain overall brain health