Alzheimer's and Dementia: The Journal of the Alzheimer's Association This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

The path forward in Alzheimer's disease therapeutics: Reevaluating the amyloid cascade hypothesis
Publication date: Available online 6 November 2019Source: Alzheimer's & DementiaAuthor(s): Martin Tolar, Susan Abushakra, Marwan SabbaghAbstractDevelopment of disease-modifying treatments for Alzheimer's disease (AD) has been challenging, with no drugs approved to date. The failures of several amyloid-targeted programs have led many to dismiss the amyloid beta (Aβ) hypothesis of AD. An antiamyloid antibody aducanumab recently showed modest but significant efficacy in a phase 3 trial, providing important validation of amyloid as a therapeutic target. However, the inconsistent results observed with aducanumab may be explain...
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - November 7, 2019 Category: Geriatrics Source Type: research

C99 selectively accumulates in vulnerable neurons in Alzheimer's disease
DiscussionThese results raise the possibility that C99, rather than Aβ plaques, is responsible for the death of nerve cells in AD. (Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association)
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - November 1, 2019 Category: Geriatrics Source Type: research

Individualized clinical management of patients at risk for Alzheimer's dementia
DiscussionIndividualized multidomain interventions may improve cognition and reduce AD/cardiovascular risk scores in patients at-risk for AD dementia. (Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association)
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - October 31, 2019 Category: Geriatrics Source Type: research

Intact global cognitive and olfactory ability predicts lack of transition to dementia
We examined if intact performance on brief cognitive and odor identification tests predicts lack of transition to dementia.MethodsIn an urban community, 1037 older adults without dementia completed the 40-item University of Pennsylvania Smell Identification Test, which includes the 12-item Brief Smell Identification Test (B-SIT). Data from 749 participants followed up for 4 years were analyzed.ResultsIn covariate-adjusted survival analyses, impairment on the Blessed Orientation Memory Concentration Test and B-SIT each predicted dementia (n = 109), primarily Alzheimer's disease (n = 101). Among participants with intact...
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - October 30, 2019 Category: Geriatrics Source Type: research

Secular trends in cognitive trajectories of diverse older adults
This study aimed to determine if later birth year influences trajectory of age-related cognitive decline across racial/ethnic groups and to test whether years of school, childhood socioeconomic status, and cardiovascular disease burden explain such secular trends.MethodsWe compared cognitive trajectories of global cognition and subdomains in two successive racially/ethnically and educationally diverse birth cohorts of a prospective cohort study.ResultsLater birth year was associated with higher initial cognitive levels for Whites and Blacks, but not Hispanics. Later birth year was also associated with less rapid rate of de...
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - October 29, 2019 Category: Geriatrics Source Type: research

Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease
We examined the neurobiological characteristics and clinical progression of these atrophy-defined subtypes.MethodsThe four subtypes were replicated using a clustering method on MRI data in 260 amyloid-β–positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [18F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline.ResultsVoxel-wise and region-of-interest analyses revealed the greatest neocortical tau load in hippocampal-sparing (frontoparietal-predominant) and typical (temporal-predo...
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - October 29, 2019 Category: Geriatrics Source Type: research

Synaptic, axonal damage and inflammatory cerebrospinal fluid biomarkers in neurodegenerative dementias
DiscussionBiomarkers of synapse and neurodegeneration differentiate HC subjects from neurodegenerative dementias and between AD, FTD, and CJD. NF-L and 14-3-3 performed similar to total tau when AT(N) system was applied. (Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association)
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - October 26, 2019 Category: Geriatrics Source Type: research

Amyloid pathology–produced unexpected modifications of calcium homeostasis in hippocampal subicular dendrites
DiscussionOverall, abnormal Ca2+ homeostasis in AD has an age dependency that comprises multiple mechanisms, including compensatory processes. (Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association)
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - October 26, 2019 Category: Geriatrics Source Type: research

New directions in clinical trials for frontotemporal lobar degeneration: Methods and outcome measures
DiscussionNew personalized endpoints that are clinically meaningful to individuals and their families should be developed. Personalized approaches to analyzing MRI data, development of new fluid biomarkers and wearable technologies will help to improve the power to detect treatment effects in FTLD clinical trials and enable new, clinical trial designs, possibly leveraged from the experience of oncology trials. A computational visualization and analysis platform that can support novel analyses of combined clinical, genetic, imaging, biomarker data with other novel modalities will be critical to the success of these endeavor...
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - October 24, 2019 Category: Geriatrics Source Type: research

Comparison of variables associated with cerebrospinal fluid neurofilament, total-tau, and neurogranin
We examined, in a community-based population (N = 777, aged 50–95) (1) what variables were associated with each of the CSF (N) markers, and (2) whether the variables associated with each marker differed by increased brain amyloid. CSF T-tau was measured with an automated electrochemiluminescence Elecsys immunoassay; NfL and Ng were measured with in-house enzyme-linked immunosorbent assays.ResultsMultiple variables were differentially associated with CSF NfL and T-tau levels, but not Ng. Most associations were attenuated after adjustment for age and sex. T-tau had the strongest association with cognition in the presence...
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - October 24, 2019 Category: Geriatrics Source Type: research

Automated sensor-based detection of challenging behaviors in advanced stages of dementia in nursing homes
DiscussionWe confirm that accelerometry can provide relevant information about challenging behaviors. We extended previous studies by differentiating various types of agitated behaviors and applying long-term measurements in a real-world setting. (Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association)
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - October 24, 2019 Category: Geriatrics Source Type: research

Targeting the ensemble of heterogeneous tau oligomers in cells: A novel small molecule screening platform for tauopathies
Publication date: Available online 22 October 2019Source: Alzheimer's & DementiaAuthor(s): Chih Hung Lo, Colin Kin-Wye Lim, Zhipeng Ding, Sanjula P. Wickramasinghe, Anthony R. Braun, Karen H. Ashe, Elizabeth Rhoades, David D. Thomas, Jonathan N. SachsAbstractObjectiveUnderstanding the heterogeneous pathology in Alzheimer's disease and related tauopathies is one of the most urgent and fundamental challenges facing the discovery of novel disease-modifying therapies. Through monitoring ensembles of toxic and nontoxic tau oligomers spontaneously formed in cells, our biosensor technology can identify tool compounds that modulat...
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - October 24, 2019 Category: Geriatrics Source Type: research

The longitudinal evaluation of familial frontotemporal dementia subjects protocol: Framework and methodology
We present the theoretical considerations of f-FTLD and the aims/objectives of this protocol. We also describe the design and methodology for evaluating and rating subjects, in which detailed clinical and neuropsychological assessments are performed, biofluid samples are collected, and magnetic resonance imaging scans are performed using a standard protocol.DiscussionThese data and samples, which are available to interested investigators worldwide, will facilitate planning for upcoming disease-modifying therapeutic trials in f-FTLD. (Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association)
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - October 19, 2019 Category: Geriatrics Source Type: research

Multicenter Alzheimer's and Parkinson's disease immune biomarker verification study
This study aimed to verify findings in cerebrospinal fluid (CSF) samples of Alzheimer's disease (AD) and Parkinson's disease (PD) subjects from the network of the European, Innovative Medicines Initiative–funded project AETIONOMY.MethodsA total of 227 samples from the studies/centres AETIONOMY, ICEBERG, and IDIBAPS were used to analyse 21 selected immunity biomarkers in CSF. Results were compared to data of an independent cohort of 399 subjects previously published.ResultsImmunity markers were predominantly and reproducibly associated with pathological levels of tau isoforms, but also with amyloid levels, aging, sex, APO...
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - October 18, 2019 Category: Geriatrics Source Type: research

Brain Aβ load association and sexual dimorphism of plasma BACE1 concentrations in cognitively normal individuals at risk for AD
DiscussionOur results suggest a sexual dimorphism in BACE1-related upstream mechanisms of brain Aβ production and deposition. We argue that plasma BACE1 should be considered in further biomarker validation and qualification studies as well as in BACE1 clinical trials. (Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association)
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - October 15, 2019 Category: Geriatrics Source Type: research