Assessment of cognition in early dementia.

Better tools for assessing cognitive impairment in the early stages of Alzheimer's disease (AD) are required to enable diagnosis of the disease before substantial neurodegeneration has taken place and to allow detection of subtle changes in the early stages of progression of the disease. The National Institute on Aging and the Alzheimer's Association convened a meeting to discuss state of the art methods for cognitive assessment, including computerized batteries, as well as new approaches in the pipeline. Speakers described research using novel tests of object recognition, spatial navigation, attentional control, semantic memory, semantic interference, prospective memory, false memory and executive function as among the tools that could provide earlier identification of individuals with AD. In addition to early detection, there is a need for assessments that reflect real-world situations in order to better assess functional disability. It is especially important to develop assessment tools that are useful in ethnically, culturally and linguistically diverse populations as well as in individuals with neurodegenerative disease other than AD.

The Collaborative Aging Research Using Technology Initiative: An Open, Sharable, Technology-Agnostic Platform for the Research Community.

INTRODUCTION: Future digital health research hinges on methodologies to conduct remote clinical assessments and in-home monitoring. The Collaborative Aging Research Using Technology (CART) initiative was introduced to establish a digital technology research platform that could widely assess activity in the homes of diverse cohorts of older adults and detect meaningful change longitudinally. This paper reports on the built end-to-end design of the CART platform, its functionality, and the resulting research capabilities. METHODS: CART platform development followed a principled design process aiming for scalability, use case flexibility, longevity, and data privacy protection while allowing sharability. The platform, comprising ambient technology, wearables, and other sensors, was deployed in participants' homes to provide continuous, long-term (months to years), and ecologically valid data. Data gathered from CART homes were sent securely to a research server for analysis and future data sharing. RESULTS: The CART system was created, iteratively tested, and deployed to 232 homes representing four diverse cohorts (African American, Latinx, low-income, and predominantly rural-residing veterans) of older adults (n = 301) across the USA. Multiple measurements of wellness such as cognition (e.g., mean daily computer use time = 160-169 min), physical mobility (e.g., mean daily transitions between rooms = 96-155), sleep (e.g., mean nightly sleep duration = 6.3-7.4 h), and level of social engagement (e.g., reports of overnight visitors = 15-45%) were collected across cohorts. CONCLUSION: The CART initiative resulted in a minimally obtrusive digital health-enabled system that met the design principles while allowing for data capture over extended periods and can be widely used by the research community. The ability to monitor and manage health digitally within the homes of older adults is an important alternative to in-person assessments in many research contexts. Further advances will come with wider, shared use of the CART system in additional settings, within different disease contexts, and by diverse research teams.

Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer's disease.

BACKGROUND: We evaluated the amounts of amyloid beta (Abeta)) peptides in the central nervous system (CNS) and in reservoirs outside the CNS and their potential impact on Abeta plasma levels and Alzheimer's disease (AD) pathology. METHODS: Amyloid beta levels were measured in (1) the plasma of AD and nondemented (ND) controls in a longitudinal study, (2) the plasma of a cohort of AD patients receiving a cholinesterase inhibitor, and (3) the skeletal muscle, liver, aorta, platelets, leptomeningeal arteries, and in gray and white matter of AD and ND control subjects. RESULTS: Plasma Abeta levels fluctuated over time and among individuals, suggesting continuous contributions from brain and peripheral tissues and associations with reactive circulating proteins. Arteries with atherosclerosis had larger amounts of Abeta40 than disease-free vessels. Inactivated platelets contained more Abeta peptides than activated ones. Substantially more Abeta was present in liver samples from ND patients. Overall, AD brain and skeletal muscle contained increased levels of Abeta. CONCLUSIONS: Efforts to use plasma levels of Abeta peptides as AD biomarkers or disease-staging scales have failed. Peripheral tissues might contribute to both the circulating amyloid pool and AD pathology within the brain and its vasculature. The wide spread of plasma Abeta values is also due in part to the ability of Abeta to bind to a variety of plasma and membrane proteins. Sources outside the CNS must be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Abeta plasma levels. Furthermore, the long-range impact of Abeta immunotherapy on peripheral Abeta sources should also be considered.

Alzheimer's Disease-Related Dementias Summit 2016: National research priorities.

Goal 1 of the National Plan to Address Alzheimer's Disease is to prevent and effectively treat Alzheimer disease and Alzheimer disease-related dementias by 2025. To help inform the research agenda toward achieving this goal, the NIH hosts periodic summits that set and refine relevant research priorities for the subsequent 5 to 10 years. This proceedings article summarizes the 2016 Alzheimer's Disease-Related Dementias Summit, including discussion of scientific progress, challenges, and opportunities in major areas of dementia research, including mixed-etiology dementias, Lewy body dementia, frontotemporal degeneration, vascular contributions to cognitive impairment and dementia, dementia disparities, and dementia nomenclature.

Studies on the effect of the apolipoprotein E genotype on the lipid profile in Alzheimer's disease.

OBJECTIVE: To determine whether Apolipoprotein E4 (Apo E4) gene status or ApoE gene dose affect the lipid profile in AD. BACKGROUND: Links between hypercholesterolemia and AD development continue to grow. Presently, limited information exists about the influence of the Apo E genotype on the lipid profile characteristics in AD. METHODS: We examined the lipid profiles (total cholesterol (TC), high-density lipoprotein (HDL), lower-density lipoprotein (LDL), TC/HDL ratio, and triglyceride (TG) levels) of 142 subjects with probable or possible AD (mean age 76.5 +/- 8.9 years), not on lipid lowering therapy by Apo E genotype. Assessment was done by gene status and gene dose. RESULTS: ApoE4 gene status did not reveal any significant differences in the lipid profile except for LDL. However, significant differences were observed by ApoE gene dose. CONCLUSION: ApoE gene status has minimal influence on the lipid panel or mean age in AD. Apo E gene dose does influence the lipid panel with Apo E 2/2, and 2/3 having significantly better lipid panels and older age of onset.

Sensitivity to expectancy violations in healthy aging and mild cognitive impairment.

In this study, individuals with mild cognitive impairment (MCI) were tested to see if executive dysfunction impacts their implementation of expectancy biases in a priming task. Young adults, healthy older adults, and individuals with MCI made speed-related decisions to sequentially presented word pairs. The proportion of category related (e.g., apple-fruit) versus coordinate related (apple-pear) pairs was varied to create different expectancy biases. When the proportion of category pairs was high (80%), the control groups showed an expectancy bias: Significant inhibition was observed for coordinate pairs compared with category pairs. The MCI group also demonstrated an expectancy bias but with much larger costs for unexpected targets. The findings suggest that individuals with MCI are inordinately sensitive to expectancy violations, and these findings are discussed in terms of possible executive dysfunction.

Recommendations of the Alzheimer's disease-related dementias conference.

The National Alzheimer's Project Act, signed into law in 2011, mandates a National Plan to Address Alzheimer's Disease that is updated annually. In the Plan, the term Alzheimer disease includes not only Alzheimer disease (AD) proper, but also several specified related dementias, namely, frontotemporal, Lewy body, vascular, and mixed dementia. In response to a specific action item in the 2012 National Plan, the National Institute of Neurological Disorders and Stroke, in collaboration with the National Institute on Aging, convened panels of experts and conducted a 2-day public conference to develop research priorities and timelines for addressing Alzheimer disease-related dementias (ADRD) in 5 topic areas: multiple etiology dementias, health disparities, Lewy body dementias including dementia with Lewy bodies and Parkinson disease dementia, frontotemporal dementia and related tauopathies, and vascular contributions to ADRD. By design, the product was up to 8 prioritized research recommendations in each topic area including estimated timelines from when work on a recommendation is started to completion or to full implementation of an ongoing activity, and recognition of shared research themes across recommendations. These included increased education and training of both researchers and health care professionals, addressing health disparities, fundamental neurobiology research, advanced diagnostics, collaborative biosample repositories, and a focus on developing effective interventions to prevent or treat ADRD by the year 2025 as targeted by the National Plan.

Case series of clinically probable dementia with Lewy bodies in two Native Americans.

While incidence and prevalence of dementias have been assessed in some tribes, little is known about whether the different types of dementias that affect whites also affect Native Americans. Here, we report 2 cases of clinically probable dementia with Lewy bodies (DLB) that fulfill McKeith Consensus Criteria in an 84-year-old full-blooded Navajo woman and a 78-year-old full-blooded Navajo male assessed in a neurology clinic.