The impact of PICALM genetic variations on reserve capacity of posterior cingulate in AD continuum

Phosphatidylinositolbinding clathrin assembly protein (PICALM) gene is one novel genetic player associated with late-onset Alzheimer’s disease (LOAD), based on recent genome wide association studies (GWAS). However, how it affects AD occurrence is still unknown. Brain reserve hypothesis highlights the tolerant capacities of brain as a passive means to fight against neurodegenerations. Here, we took the baseline volume and/or thickness of LOAD-associated brain regions as proxies of brain reserve capacities and investigated whether PICALM genetic variations can influence the baseline reserve capacities and the longitudinal atrophy rate of these specific regions using data from Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. In mixed population, we found that brain region significantly affected by PICALM genetic variations was majorly restricted to posterior cingulate. In sub-population analysis, we found that one PICALM variation (C allele of rs642949) was associated with larger baseline thickness of posterior cingulate in health. We found seven variations in health and two variations (rs543293 and rs592297) in individuals with mild cognitive impairment were associated with slower atrophy rate of posterior cingulate. Our study provided preliminary evidences supporting that PICALM variations render protections by facilitating reserve capacities of posterior cingulate in non-demented elderly

Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis

Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions

Estrogen replacement therapy, Alzheimer's disease, and mild cognitive impairment.

This article highlights the latest findings regarding estrogen replacement therapy in the treatment and prevention of Alzheimer's disease (AD) and mild cognitive impairment in women. Despite considerable evidence from observational studies, recent randomized clinical trials of conjugated equine estrogens, alone and in combination with progestin, have shown no benefit for either the treatment of established AD or for the short-term prevention of AD, mild cognitive impairment, or cognitive decline. Based on the evidence, there is no role at present for estrogen replacement therapy in the treatment or prevention of AD or cognitive decline, despite intriguing results from the laboratory and from observational studies. However, numerous questions remain about the biologic effects of estrogens on brain structure and function. Additional basic and clinical investigations are necessary to examine different forms and dosages of estrogens, other populations, and the relevance of timing and duration of exposure

Apolipoprotein-E Genotyping of Diabetic Dementia Patients: Is Diabetes Rare in Alzheimer\u27s Disease?

OBJECTIVES: To determine whether diabetes is rare in Alzheimer disease (AD) relative to other types of dementia and whether diabetics with dementia have a low frequency of the Apolipoprotein-E E4 genotype. DESIGN: Observational survey study. SETTING: An Irvine, California, outpatient dementia assessment center. PARTICIPANTS: A total of 123 patients with AD, 51 with vascular dementia, 57 with mixed vascular dementia and AD, and 34 with other dementias (non-vascular non-AD). MEASUREMENTS: Demographic data; histories and evidence of diabetes, hypertension, heart disease, stroke; and Apolipoprotein-E genotype for 95 cases distributed across the groups. RESULTS: There were 15 diabetics in the sample (5.7%), all of whom had extensive vascular disease. Diabetes was rare in AD patients (0.8%) relative to vascular dementia (11.8%), mixed vascular/AD dementia (8.8%), and other dementia patients (8.8%). In addition, the E4 allele of apolipoprotein-E, associated with high risk for AD, was frequent in the AD group (71.4%), but in the diabetic group it was only as frequent as in the general population (38.5%). In the diabetics with E4, 60% (3/5) had mixed dementia. CONCLUSIONS: Diabetics with dementia rarely have AD except as a component of mixed dementia. Apo-E genotyping showed only average E4 allele frequency in diabetics compared with the high E4 frequency found in AD patients. However, mixed dementia in diabetics may be associated with the E4 allele, suggesting that close control of diabetes may be particularly important for those with E4 since they may be more likely than others to develop both diseases

Venous thromboembolism knowledge among older post-hip fracture patients and their caregivers.

Patient education about venous thromboembolism (VTE) prevention is needed to prevent complications and costly re-hospitalization. Nurses are uniquely positioned to provide vital education as patients transition from the inpatient setting to after discharge. Still, little is known about patient knowledge deficits and those of their caregivers. The purpose of this study was to explore VTE prevention knowledge in a sample of older hip fracture patients and family caregivers. At the time of hospital discharge, surveys were completed by hip fracture surgery patients (≥65; n=30) and family caregivers (n=30). Participants reported needs for more prophylactic anticoagulation and side effects education. Mean education satisfaction was 3.49 out of 5 among patients and 3.83 among caregivers. Focused patient education regarding the wisdom of VTE prevention, potential risks involved, and patient and caregiver roles in advocating for better prevention measures is needed for these patients at risk for hospital readmission secondary to VTE

Venous thromboembolism knowledge among older post-hip fracture patients and their caregivers.

Patient education about venous thromboembolism (VTE) prevention is needed to prevent complications and costly re-hospitalization. Nurses are uniquely positioned to provide vital education as patients transition from the inpatient setting to after discharge. Still, little is known about patient knowledge deficits and those of their caregivers. The purpose of this study was to explore VTE prevention knowledge in a sample of older hip fracture patients and family caregivers. At the time of hospital discharge, surveys were completed by hip fracture surgery patients (≥65; n=30) and family caregivers (n=30). Participants reported needs for more prophylactic anticoagulation and side effects education. Mean education satisfaction was 3.49 out of 5 among patients and 3.83 among caregivers. Focused patient education regarding the wisdom of VTE prevention, potential risks involved, and patient and caregiver roles in advocating for better prevention measures is needed for these patients at risk for hospital readmission secondary to VTE