Effects of Rice Wine Lees on Cognitive Function in Community-Dwelling Physically Active Older Adults: A Pilot Randomized Controlled Trial Abstract Background Rice wine lees (RWL), a Japanese traditional fermented product, is a rich source of one-carbon metabolism-related nutrients, which may have beneficial effects on cognitive function. Objectives We aimed to examine the effect of the RWL on cognitive function in community-dwelling physically active older adults. Design Double-blind, randomized, placebo-controlled study (clinical trial number: UMIN 000027158). Setting Community-based intervention including assessments conducted at the University of Hyogo and a public liberal arts school in Himeji City, Japan. Participants A total of 35 community-dwelling older adults (68–80 years) who performed mild exercise before and during the trial were assigned to either the RWL (n=17) or the placebo group (n=18). Intervention Daily consumption of 50 g RWL powder, which contained one-carbon metabolism-related nutrients, or the placebo powder (made from soy protein and dextrin) for 12 weeks. Both supplements included equivalent amounts of energy and protein. Measurements Montreal Cognitive Assessment, computerized cognitive function test, and measurements of serum predictive biomarkers (transthyretin, apolipoprotein A1, and complement C3) were conducted at baseline and follow-up. Results Visual selective attention and serum transthyretin significantly improved in the RWL group, whereas there was no significant change in the placebo group. No significant group difference was observed in the remaining cognitive performance tests. Conclusions RWL supplements seem to have a few effects on cognitive function in community-dwelling physically active older adults. However, the impact was limited; therefore, further studies with sufficient sample size are warranted to elucidate this issue.

Association of Vitamin D Levels with Incident All-Cause Dementia in Longitudinal Observational Studies: A Systematic Review and Meta-analysis Abstract Background The role of vitamin D is not only limited to bone health and pathogenesis of chronic diseases. Evidence now suggests that it is also involved in the development of various dementias and Alzheimer’s disease (AD). Objective To carry out a systematic review and meta-analysis to evaluate the association between vitamin D levels and increased risk of incident all-cause dementia in longitudinal studies. Design We conducted a systematic review and meta-analysis using the electronic bibliographic databases PubMed and Scopus. Setting Prospective cohort studies. Participants Community-dwelling older adults. Measurements Vitamin D serum concentrations were categorized in three groups: normal levels (>50 nmol/L), insufficient levels (25–49.9 nmol/L), and deficient levels (<25 nmol/L). We performed a meta-analysis using the general inverse variance method to calculate the pooled risk of AD and all-cause dementia according to vitamin D levels. Random-effects or fixed-effect model were used to calculate the pooled risk based on the heterogeneity analysis. Results Five studies were included in the meta-analysis. The pooled risk of all-cause dementia and AD was significantly higher in those with deficient serum vitamin D level compared to those with normal level (1.33, CI95% [1.15, 1.54], and 1.87, CI95% [1.03, 3.41], respectively). Those with insufficient level also had a higher pooled risk of all-cause dementia and AD, but the strength of association was less robust (1.14 CI95% [1.02, 1.27] and 1.25, CI95% [1.04–1.51], respectively). Conclusion We found a gradient effect for the risk of all-cause dementia and AD according to the vitamin D level, with higher risk in those in the deficient levels group and intermediate risk in those with insufficient levels. Our findings were limited by the relatively small number of studies included in the meta-analysis and their geographic restriction.

Associations of Later-Life Education, the BDNF Val66Met Polymorphism and Cognitive Change in Older Adults Abstract In 358 participants of the Tasmanian Healthy Brain Project, we quantified the cognitive consequences of engaging in varying loads of university-level education in later life, and investigated whether or not BDNF Val66Met affected outcomes. Assessment of neuropsychological, health, and psychosocial function was undertaken at baseline, 12-month, and 24-month follow-up. Education load was positively associated with change in language processing performance, but this effect did not reach statistical significance (P = 0.064). The BDNF Val66Met polymorphism significantly moderated the extent to which education load was associated with improved language processing (P = 0.026), with education load having a significant positive relationship with cognitive change in BDNF Met carriers but not in BDNF Val homozygotes. In older adults who carry BDNF Met, engaging in university-level education improves language processing performance in a load-dependent manner.

Effects of a Group-Based 8-Week Multicomponent Cognitive Training on Cognition, Mood and Activities of Daily Living among Healthy Older Adults: A One-Year Follow-Up of a Randomized Controlled Trial Abstract Background Cognitive interventions have the potential to enhance cognition among healthy older adults. However, little attention has been paid to the effect of cognitive training (CT) on mood and activities of daily living (ADL). Objectives To assess the effectiveness of a multicomponent CT using a training program of executive functions, attention, memory and visuospatial functions (TEAM-V Program) on cognition, mood and instrumental ADL. Design A randomized, single-blinded, treatment-as-usual controlled trial. Setting Geriatric clinic in Bangkok, Thailand. Participants 77 nondemented community-dwelling older adults (mean age 65.7±4.3 years). Intervention The CT (TEAM-V) program or the treatmentas- usual controlled group. The TEAM-V intervention was conducted over 5 sessions, with a 2-week interval between each session. Of 77 participants randomized (n=40 the TEAM-V program; n=37 the control group). Measurements The Thai version of Montreal Cognitive Assessment (MoCA), The Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Thai version of Hospital Anxiety and Depression Scale (HADS) and The Chula ADL were used to assess at baseline, 6 months and 1 year. Results Compared with the control arm, the TEAM-V Program was associated with reducing anxiety (P = 0.004). Compared with the baseline, participants receiving the TEAM-V Program were associated with significantly improved general cognition (MoCA, P < 0.001), immediate recall (word recall task, P = 0.01), retrieval and retention of memory process (word recognition task, P = 0.01), attention (number cancellation part A, P < 0.001) and executive function (maze test, P = 0.02) at 1 year. No training effects on depression (P = 0.097) and IADL (P = 0.27) were detected. Conclusions The TEAM-V Program was effective in reducing anxiety. Even though, the program did not significantly improve cognition, depression and ADL compared with the control group, global cognition, memory, attention and executive function improved in the intervention group compared with baseline. Further studies incorporating a larger sample size, longitudinal follow-up and higher-intensity CT should be conducted.

Multidomain Interventions to Prevent Cognitive Impairment, Alzheimer’s Disease, and Dementia: From FINGER to World-Wide FINGERS Abstract Alzheimer’s disease (AD) and dementia are a global public health priority, and prevention has been highlighted as a pivotal component in managing the dementia epidemic. Modifiable risk factors of dementia and AD include lifestyle-related factors, vascular and metabolic disorders, and psychosocial factors. Randomized controlled clinical trials (RCTs) are needed to clarify whether modifying such factors can prevent or postpone cognitive impairment and dementia in older adults. Given the complex, multifactorial, and heterogeneous nature of late-onset AD and dementia, interventions targeting several risk factors and mechanisms simultaneously may be required for optimal preventive effects. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is the first large, long-term RCT to demonstrate that a multidomain lifestyle-based intervention ameliorating vascular and lifestyle-related risk factors can preserve cognitive functioning and reduce the risk of cognitive decline among older adults at increased risk of dementia. To investigate the multidomain intervention in other populations and diverse cultural and geographical settings, the World-Wide FINGERS (WW-FINGERS) network was recently launched (https://alz.org/wwfingers). Within this network, new FINGER-type trials with shared core methodology, but local culture and context-specific adaptations, will be conducted in several countries. The WW-FINGERS initiative facilitates international collaborations, provides a platform for testing multidomain strategies to prevent cognitive impairment and dementia, and aims at generating high-quality scientific evidence to support public health and clinical decision-making. Furthermore, the WW-FINGERS network can support the implementation of preventive strategies and translation of research findings into practice.

Feasibility of Using a Wearable Biosensor Device in Patients at Risk for Alzheimer’s Disease Dementia Abstract Background Alzheimer’s disease (AD) is the most common and most costly chronic neurodegenerative disease globally. AD develops over an extended period prior to cognitive symptoms, leaving a “window of opportunity” for targeted risk-reduction interventions. Further, this pre-dementia phase includes early physiological changes in sleep and autonomic regulation, for which wearable biosensor devices may offer a convenient and cost-effective method to assess AD-risk. Methods Patients with a family history of AD and no or minimal cognitive complaints were recruited from the Alzheimer’s Prevention Clinic at Weill Cornell Medicine & New York-Presbyterian. Of the 40 consecutive patients screened, 34 (85%) agreed to wear a wearable biosensor device (WHOOP). One subject (2.5%) lost the device prior to data collection. Of the remaining subjects, 24 were classified as normal cognition and were asymptomatic, 6 were classified as subjective cognitive decline, and 3 were amyloid-positive (one with pre-clinical AD, one with pre-clinical Lewy-Body Dementia, and one with mild cognitive impairment due to AD). Sleep-cycle, autonomic (heart rate variability [HRV]) and activity measures were collected via WHOOP. Blood biomarkers and neuropsychological testing sensitive to cognitive changes in pre-clinical AD were obtained. Participants completed surveys assessing their sleep-patterns, exercise habits, and attitudes towards WHOOP. The goal of this prospective observational study was to determine the feasibility of using a wrist-worn biosensor device in patients at-risk for AD dementia. Unsupervised machine learning was performed to first separate participants into distinct phenotypic groups using the multivariate biometric data. Additional statistical analyses were conducted to examine correlations between individual biometric measures and cognitive performance. Results 27 (81.8%) participants completed the follow-up surveys. Twenty-four participants (88.9%) were satisfied with WHOOP after six months, and twenty-three (85.2%) wanted to continue wearing WHOOP. K-means clustering separated participants into two groups. Group 1 was older, had lower HRV, and spent more time in slow-wave sleep (SWS) than Group 2. Group 1 performed better on two cognitive tests assessing executive function: Flanker Inhibitory Attention/Control (FIAC) (p=.031), and Dimensional Change Card Sort (DCCS) (p=.061). In Group 1, DCCS was correlated with SWS (ϱ=.68, p=0.024) and HRV (ϱ=.6, p=0.019). In Group 2, DCCS was correlated with HRV (ϱ=.55, p=0.018). There were no significant differences in blood biomarkers between the two groups. Conclusions Wearable biosensor devices may be a feasible tool to assess AD-related physiological changes. Longitudinal collection of sleep and HRV data may potentially be a noninvasive method for monitoring cognitive changes related to pre-clinical AD. Further study is warranted in larger populations.

Erratum to: Alzheimer’s Disease Composite Score: a Post-Hoc Analysis Using Data from the LipiDiDiet Trial in Prodromal Alzheimer’s Disease The article «Alzheimer’s Disease Composite Score: a Post-Hoc Analysis Using Data from the LipiDiDiet Trial in Prodromal Alzheimer’s Disease», written by S.B. Hendrix, H. Soininen, A.M.J. van Hees, N. Ellison, P.J. Visser, A. Solomon, A. Attali, K. Blennow, M. Kivipelto, T. Hartmann, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 10 September 2019 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed to © The Author(s) 2019 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made. The original article was corrected.

Health Literacy in Individuals at Risk for Alzheimer’s Dementia: A Systematic Review Abstract Background Health literacy (HL) refers to the capacity to access, understand, appraise and apply information for decision-making and acting in health-related matters. In the field of Alzheimer’s disease (AD), expanding technologies of early disease detection, disease course prediction and eventually personalized prevention confront individuals at-risk with increasingly complex information, which demand substantial HL skills. Here we report current findings of HL research in at-risk groups. Methods Search strings, referring to HL, AD, amyloid and risk, were developed. A systematic review was conducted in PUBMED, Cochrane Library, PsycINFO, and Web of Science to summarize the state of evidence on HL in at-risk individuals for Alzheimer’s dementia. Eligible articles needed to employ a validated tool for HL, mention the concept or one dimension (access, understand, appraise and apply information for decision-making and acting). Results 26 quantitative and 9 qualitative studies addressing at least one dimension of HL were included. Overall, there is evidence for a wish to gain knowledge about the own brain status and risk of dementia. Psychological distress may occur and the subjective benefit-risk estimation may be modified after risk disclosure. Effects on lifestyle and planning may occur. Overall understanding and appraisal of information related to AD risk seem variable with several impacting factors. In mild cognitive impairment (MCI) basic HL skill seem to be affected by cognitive dysfunction. Conclusions Systematic assessment of HL in at-risk population for AD is sparse. Findings indicate the paramount importance of adequate communication with persons at risk, being sensitive to individual needs and preferences. Substantial research needs were identified.

Longitudinal Comparison of in Clinic and at Home Administration of the Cogstate Brief Battery and Demonstrated Practice Effects in the Mayo Clinic Study of Aging Abstract Background The Cogstate Brief Battery (CBB) is a computerized cognitive assessment that can be completed in clinic or at home. Design/Objective This retrospective study investigated whether practice effects / performance trajectories of the CBB differ by location of administration. Participants/Setting Participants included 1439 cognitively unimpaired individuals age 50–75 at baseline participating in the Mayo Clinic Study of Aging (MCSA), a population-based study of cognitive aging. Sixty three percent of participants completed the CBB in clinic only and 37% completed CBB both in clinic and at home. Measurements The CBB consists of four subtests: Detection, Identification, One Card Learning, and One Back. Linear mixed effects models were used to evaluate performance trajectories in clinic and at home. Results Results demonstrated significant practice effects between sessions 1 to 2 for most CBB measures. Practice effects continued over subsequent testing sessions, to a lesser degree. Average practice effects/trajectories were similar for each location (home vs. clinic). One Card Learning and One Back accuracy performances were lower at home than in clinic, and this difference was large in magnitude for One Card Learning accuracy. Participants performed faster at home on Detection reaction time, although this difference was small in magnitude. Conclusions Results suggest the location where the CBB is completed has an important impact on performance, particularly for One Card Learning accuracy, and there are practice effects across repeated sessions that are similar regardless of where testing is completed.

Can Digital Technology Advance the Development of Treatments for Alzheimer’s Disease? Abstract The report explores the potential digital technology has to generate novel endpoints and digital biomarkers for Alzheimer’s disease drug development studies. Drawing from literature and novel pilots, we explore the value of innovative digital technology to digitize physiological behaviours such as sleep disturbance and gait changes. Technology now exists to monitor and quantify our use and interaction with electronics in the home, the use of social platforms and smart-phones, geolocation, sleep and activity patterns. These multimodal digital data are a feasible alternative to capturing the more complex activities of daily living that require higher cognitive processes and are a sensitive predictor of disease. The combination of biosensors and the internet of things (IoT), offers the potential to collect highly relevant, objective data in a continuous, passive and low burden manner. Digital endpoints and biomarkers could have value in the diagnosis, monitoring and development of therapies for patients living with Alzheimer’s disease.