Risk Factor For Cognitive Decline Research Articles

CO-DESIGNING A GREEN ACTIVITY PRESCRIPTION PROGRAM WITH HISPANIC/LATINO PERSONS LIVING WITH MEMORY CHALLENGES

Abstract Nature activities can improve well-being and may modify risk factors for cognitive decline. There is a gap between nature activities offered within a person’s community and their ability to participate in them, including Hispanic/Latino persons living with memory challenges (MCI and mild dementia) in urban lower-resourced areas. An occupational therapist can bridge this gap by tailoring nature activities available in a person’s home, neighborhood, and community to their interests and needs. Utilizing a participatory approach, we sought to co-design a 12-week Green Activity Prescription (GAP-H) with Hispanic/Latino individuals living with memory challenges and their care partners. Participants were recruited via convenience and snowball sampling in the Bronx, NY with outdoor activity professionals (n=7), Hispanic/Latino persons living with memory challenges and care partners (n=5), and interdisciplinary healthcare providers/dementia experts (n=7). Co-design occurred iteratively with 5 focus groups and 2 individual interviews lasting 30-90 minutes and focused on intervention and research design. Sessions were recorded and transcribed. Utilizing directed content analysis data was coded using a priori codes intervention design and research design. Participant preferences for intervention design were captured by subcodes session duration (30-90 minutes), frequency (4-8 sessions), and delivery modes (in-person and phone). Participants’ preferred nature activities included group exercise and outdoor crafts [crocheting], outcomes of well-being, social participation, decreased loneliness, and stewardship were identified. Preferred language for recruitment materials were memory challenges, Hispanic/Latino, and well-being. Referral pathways were identified including community-based organizations and primary care. Findings can inform the co-design process of other interventions for this population.

LEVERAGING NEIGHBORHOOD EXPOSURES AS MODIFIERS OF INDIVIDUAL RISK FACTORS FOR COGNITIVE DECLINE AND DEMENTIAS

Abstract There are numerous ways in which neighborhood environmental factors have been shown to contribute to adverse health. More remains to be done to link long-term neighborhood exposures, such as social and physical activities, to modifiable individual risk factors for cognitive decline and dementia. Individual interventions are usually small in scale and conducted in those with higher socioeconomic status (SES). Additionally, increases in healthy behaviors, such as walking, have been difficult to promote and sustain. Each of these risk factors is known to be influenced by environmental features. This symposium will explore the roles of neighborhood-level social (nSES, affluence, cohesion, discrimination) and physical (air pollution) factors as drivers of cognitive aging and dementia across multiple longitudinal studies of community-based aging. Studies span urban and rural communities, including the Health ABC Study, the Cardiovascular Health Study, and the Think Phresh study. These studies are important to evaluating the role of neighborhood features on cognitive aging by expanding beyond cross-sectional data and by studying residentially stable older adults most likely to be affected by their local context. Those neighborhood factors that impact individual activity, cognitive aging, and Alzheimer’s disease risk will be further discussed for differences by race/ethnicity.

A Scoping Review of the Effects of Ambient Air Quality on Cognitive Frailty

Environmental and public health research has given considerable attention to the impact of air quality on brain health, with systematic reviews being widespread. No literature review has been conducted for cognitive frailty—a multidimensional syndrome combining physical frailty and cognitive impairment and their apparent co-dependence, linked to increased vulnerability and adverse health outcomes, including dementia. Instead, cognitive decline and frailty are implicitly explored through research on air quality and comorbid cognitive and physical decline in elderly populations. A scoping review was conducted to explore the need for a systematic review. Combining the Arksey and O’Malley, and PRISMA-ScR checklist, a scoping review of SCOPUS using ‘cogniti*’ + ‘resilience’ + ‘air quality’ or ‘cogniti*’ + ‘ageing’ + ‘air quality’ resulted in n = 2503 articles, screened and reduced using inclusion and exclusion criteria, to n = 16 articles. Air quality appears to be a critical risk factor for cognitive decline, even at air quality levels below WHO targets. Moderate long-term ambient air pollution appears linked to increased risk of cognitive frailty, suggesting earlier and more active interventions to protect older people. There are varied effects on cognition across the life course, with both emotional and functional impacts. Effects may be more detrimental to elderly people with existing conditions, including economic and health inequalities. Generalisation of results is limited due to the absence of a dose–response, variations in methods, controlling for comorbid effects, and variance across studies. No literature review has been performed for cognitive frailty, largely due to the fact that it is not presently treated as an explicit outcome. The findings support the need for more research and a more extensive summary of the literature but suggest that there is worsening cognitive function over the life course as a result of increased PM2.5 concentrations. Furthermore, air quality appears to be a critical risk factor even at levels below World Health Organisation targets.

Hearing Loss as a Risk Factor for Cognitive Decline in the Elderly: A Rapid Review

Purpose: The aim of this rapid review was to identify and evaluate evidence exploring hearing loss as a risk factor for cognitive decline in the elderly population. Methods: A literature search was performed in three databases: CINAHL, Cochrane Central, and PubMed. The PRISMA template was used to record the search and selection process. Search criteria included older adults aged 65 and up with diagnosed or self-reported hearing loss and no previous diagnosis of dementia or Alzheimer’s disease. Participants were excluded if they had been diagnosed with dementia or tested for it before the study began. Hearing loss was categorized using the pure tone average (PTA): normal (/= 25-40 dB), and moderate to severe impairment (> 40 dB). Selected research studies were critically appraised using the JBI checklist. A custom data extraction form was used to record inclusion/exclusion criteria, PICO data elements, risk of bias, and level of evidence. Results: Three longitudinal cohort studies met the inclusion criteria. The Joanna Briggs Institute evidence hierarchy was used to rate the level and quality of the studies. Results of the rapid review indicate the quality of studies a high or moderately high. A summary of the results for each study is provided. Clinical Implications: This review contributes to the growing body of literature suggesting that untreated hearing loss is a risk for cognitive decline. While there are various hypotheses on whether there is a definitive relationship between the two, many of the studies reviewed found that a hearing loss in older adults will result in a poorer change of cognitive ability or cognitive decline. Any patient aged 65 years or more indicating concern about hearing loss should be referred to an audiologist for a comprehensive hearing evaluation.

Update of the “LIfestyle for BRAin health” (LIBRA) index: Results from an umbrella review and Delphi consensus study on modifiable dementia risk factors

AbstractBackgroundGiven the projected increase in the number of people with dementia and the lack of curative treatment, there is increasing attention to the contribution of modifiable risk and protective factors to dementia risk. In 2015, the “LIfestyle for BRAin health" (LIBRA) index was developed based on the results of a systematic literature review and Delphi expert study (Deckers et al., 2015). LIBRA consists of twelve modifiable risk factors for cognitive decline and dementia. Although this risk index has been well‐validated for cognitive decline and dementia risk in numerous population‐based cohorts and intervention studies, newly emerged risk factors might ask for an update (Deckers et al., 2019; Deckers et al., 2020).MethodTo update LIBRA, we conducted an umbrella review to assess all systematic reviews (SR) and meta‐analyses (MA) on modifiable dementia risk factors published between January 2015 and June 2021 in four databases (Pubmed, Embase, Web of Science, and PsychINFO). In parallel, a two‐round Delphi expert study was conducted. In the first round (May‐June 2022), eighteen dementia experts were asked to evaluate the factors currently included in LIBRA. Additionally, we asked to list new modifiable factors not previously included in LIBRA. In the second round (December 2022‐January 2023), the experts ranked the most important risk factors identified in the umbrella review and first Delphi round.ResultThe search returned 6,540 hits, of which 147 SR/MA were included in our umbrella review. Next to the existing LIBRA factors, new candidate risk factors that were consistently associated with increased risk for cognitive decline and dementia included: low social engagement, hearing impairment, vision impairment, atrial fibrillation, and anxiety. After triangulation of the results of the umbrella review and the first Delphi round, the experts identified hearing impairment, lifecourse inequalities, social contact, atrial fibrillation, and sleep as the most important new modifiable risk factors in the second Delphi round.ConclusionSeveral new modifiable risk factors for cognitive decline and dementia have been identified in this umbrella review and Delphi consensus study. These factors will be used for updating the existing LIBRA index, which will subsequently be externally validated in population‐based cohort studies.

Association between Aluminium Levels and Cognitive Decline in Environmentally Exposed Elders

AbstractBackgroundNormal brain functioning depends on metals homeostasis, as imbalances may increase oxidative stress and cause other detrimental intracellular events that lead to cell loss. Furthermore, environmental exposure to toxic metals is hypothesized to induce neuroinflammation and neuropathology, paving the way to neurodegeneration. The aim of this study was to examine whether such Potentially Toxic Elements (PTE) are associated with cognitive performance over time in a sample of elderly individuals of environmentally contaminated regions.MethodA total of 146 elders permanently residing in environmental risk areas were recruited. Participants completed the Mini Mental State Examination (MMSE) for cognitive assessment and were biomonitored for several PTE through hair and urine analysis. After 5 years, the cognitive assessment was repeated.ResultCognitive performance significantly declined from baseline to follow‐up (p < 0.001), with participants scoring on average 4.41 less points on MMSE (Baseline: M = 25.79, SD = 3.520, Md = 27.00; Follow‐up: M = 21.38, SD = 5.343, Md = 21.00). Regression analysis on the relationship between PTE and cognitive performance revealed that Aluminium (β = ‐0.322, p = 0.32) and Zinc (β = ‐0.372, p = 0.15) in hair and Aluminium in urine (β = ‐0.368, p = 0.010) significantly predicted MMSE scores past 5 years of biomonitoring (p = 0.002). Higher contents of these PTE were associated with worse cognitive performance at follow‐up, after controlling the effects of age, education and supplement intake.ConclusionHigher levels of Aluminium significantly predict worse general cognitive performance 5 years after biomonitoring across different biological samples. Environmental exposure to this metal may constitute a risk factor for cognitive decline.

Multimodal Neuromarkers Predict Successful Physical Activity Engagement in Older Adults with Vascular Disease

AbstractBackgroundPhysical inactivity is a significant risk factor for cognitive decline, particularly in vulnerable populations including those with cardiovascular risk‐factors1. To better understand the mechanisms that support positive physical activity engagement, the current study aimed to evaluate whether neuromarkers can predict future change in physical activity among older adults with a newly diagnosed cardiovascular risk‐factor.MethodWe analyzed baseline resting‐state functional and structural magnetic resonance imaging (MRI) data from the UK‐Biobank, a large population longitudinal cohort (n = 365; mean age = 62.10 years ± 6.5; cognitively normal). Brain imaging was obtained at baseline, and physical activity data was obtained at baseline and follow‐up after 5 years. Inclusion criteria were a new diagnosis of a cardiovascular risk factor (hypertension, type‐II diabetes‐mellitus, dyslipidemia, cardiac angina or myocardial infarction) between baseline and follow‐up; and did not meet the World Health Organization recommended 150 minutes/week of moderate or 75 minutes/week of vigorous physical activity at baseline. Demographic variables including age, sex, and education were included as covariates of non‐interest.To assess whether baseline resting‐state brain imaging predicts future change in physical activity behaviour, we performed a kernel‐ridge‐regression model with 5‐fold nested‐cross‐validation. Preprocessed neuroimaging data was used as input for the analysis, and the machine‐learning pipeline included feature reduction using grid‐search, hyperparameter selection, and model‐building: the model predicts whether test subject successfully increased physical activity engagement at follow up (reported above 150 min/week moderate or 75 min/week vigorous physical activity). Permutation‐testing (100 times) was performed before evaluating prediction metrics using accuracy and Receiver Operating Characteristic curves.ResultOur prediction model delivered an accurate performance with average accuracy of 0.861 ± 3.8, and 0.883 ± 4.2 area under the curve (AUC) in predicting future behaviour change from physically inactive at baseline to physically active in follow up.ConclusionThese results show baseline brain imaging can accurately predict physical activity behavior change in older adults with new cardiovascular disease. Leveraging machine‐learning methods to predict future lifestyle engagement will help characterize the neural mechanisms that support successful lifestyle change after a new cardiovascular diagnosis.1. Gallen et al. Trends in Cog Sci. 2019

P212: The characteristics of neuropsychiatric symptom in mild cognitive impairment with diabetes mellitus

Objective:Diabetes mellitus (DM) is known to be one of the risk factors for cognitive decline and dementia. Neuropsychiatric symptom (NPS) is present not only in dementia, but also mild cognitive impairment (MCI). In this study, we examined NPS of MCI with DM and compared MCI with DM and our MCI database to investigate the characteristics of MCI with DM.Methods:The participants were subjects who were diagnosed as MCI from type 2 DM participants enrolled in Osaka University Hospital. To estimate NPS, we used Neuropsychiatric Inventory (NPI) score.Results:The number of MCI subjects with DM who were estimated NPS was 19. According to the NPI score, apathy is the most severe symptom in MCI (average score = 2.5±3.3). This result was the same as the score of our database. In the frequency of NPS, there was no difference between the results in NPI of MCI with DM and MCI of our data (n = 225) except for sleep disturbance and appetite/eating disturbance (chi-squared test, P < 0.05). The sleep disturbance was more frequent in MCI with DM than in MCI of our database. On the other hand, the appetite/eating disturbance was less frequent in in MCI with DM than in MCI of our database. Moreover, the appetite/eating disturbance was not observed in MCI with DM.Conclusion:NPS of MCI with DM is almost the same as MCI of our database except for sleep disturbance and appetite/eating disturbance. This result might be influenced by the disorder of lifestyle habits that is often observed in patients with DM or cognitive impairment of DM.The limitation of our study is the small number of cases, further investigation is needed.

The potential of immersive auditory‐cognitive training as a platform for studying hearing‐loss and cognitive decline

AbstractBackgroundHearing loss (HL) is considered one of the top modifiable risk factors for cognitive decline and dementia. However, modifiability is still a challenge, with auditory‐cognitive training (ACT) representing a promising approach on top of hearing devices, although generalizability and transfer effects of such trainings remain a challenge.MethodThe objective of this study is to gain insights into the benefits of an ACT in audio‐visual immersion with the goal to improve speech comprehension in older adults at‐risk for dementia. Participants (with varying degrees of cognitive capacity and pure‐tone HL) answer questions about spoken content in a three‐dimensional immersive (virtual reality and stereoscopic stimulus presentation) conversation. Electroencephalography is used to measure neural responses simultaneously. Speech comprehension is measured on a behavioral level and concurrently cortical responses to speech as a function of baseline cognitive capacity, audiometric measures and varying cognitive demand is assessed. We address the challenge of generalizability and transferability by enriching our training with natural, relatable speech content, and increased immersion simulating day‐by‐day speech situations.ResultWe predict improved speech comprehension post immersive ACT and simultaneously gain a deeper understanding of the associated neural responses to speech with varying cognitive demands. We further intend to model these effects as a function of baseline cognitive capacity and degree of pure‐tone HL (data collection will start February 2022).ConclusionThe central objective is whether immersive ACT has the potential to improve speech comprehension and to what extent such benefits depend on individual cognitive capacity and pure‐tone HL in older adults at‐risk for dementia. The design allows for both a within‐ and a between‐person perspective, whereby individual prerequisites, environmental and motivational factors will be considered. Finally, it allows for valuable considerations for future trainings, particularly regarding transferability and generalizability, while enabling increased engagement of individuals.

Determinants of Cognitive Trajectories in Lower Educated Older Adults: Evidence from Brazil.

AbstractBackgroundPatterns of cognitive change and modifiable factors for declining versus stable cognitive trajectories have rarely been described in a lower‐educated older population. Our goal was to identify heterogeneous long‐term trajectories of cognitive functioning and explore possible factors associated with cognitive decline beyond education, among older Brazilian adults.MethodWe used data on n = 1,042 adults aged ≥ 60 from the Health, Welfare and Aging (SABE) without cognitive impairment at baseline over four waves (2000‐2015) in São Paulo, Brazil. We applied group‐based trajectory modelling to identify cognitive trajectories. Cognition was measured using the abbreviated version of the Mini‐Mental State Examination (MMSE).ResultWe identified three cognitive groups: stable (n = 754), mild declining (n = 183), and strongly declining (n = 105). The probability of being in the strongly declining group membership was 10.7%. According to the MMSE classification, the mild declining group reached the average threshold for cognitive impairment on the last follow‐up, while the strongly declining group was on the second follow‐up. Furthermore, respondents in the stable trajectory were more likely to report more than primary education, to be white and married, to earn more than four times the minimum wage/month, to live in urban areas during childhood, and to practice vigorous physical activity at least three times a week. On the other hand, those in the strongly declining trajectory were more likely to identify as black or mixed, to self‐report subjective emptiness, and to have lower BMI, diabetes, and stroke. Moreover, both mild and strongly declining participants presented higher average age and lower MMSE scores at baseline compared to the stable trajectory. The multinomial logistic regression analysis revealed that respondents who self‐reported being mixed, had higher age, had primary education, had a stroke, and smoked at baseline were more likely to be in the strongly declining group.ConclusionOur findings suggest that besides education, interventions to reduce cognitive decline might include health and social policies addressing inequalities and modifiable risk factor burdens to improve later‐life cognitive functioning of at‐risk individuals. Sample attrition suggests estimates of the magnitude of the risk factors for cognitive decline to be conservative.

Exploratory Factor Analysis of Neuropsychological Test Data as Measured by the Original and Extended Version of the Alzheimer’s Disease Assessment Scale in the SIU Longitudinal Cognitive Aging Study

AbstractBackgroundThe original Alzheimer’s disease Assessment Scale (oADAS) has been used to measure cognitive aging in Alzheimer’s disease (AD) since the 1980s and is considered the gold standard for assessing the efficacy of novel treatments for AD. However, the oADAS has been criticized for not being sensitive to predementia syndromes such as mild cognitive impairment (MCI) due to the ceiling effects of many of the ADAS subtests. In the present study, we used Exploratory Factor Analysis (EFA) to determine the underlying factor structure of the oADAS and a novel extended version of this measure (eADAS).MethodWe included data from 978 participants who were enrolled in the SIU LCAS as controls. The majority of the cohort was White/Non‐Hispanic (97.2%) and female (66.4%). Participants had a mean age of 66.1 years and a mean education of 14.6 years. The oADAS was administered using standardized methods. All of the subtest data was converted back from error scores to raw scores and standardized using z‐score transformation. EFA with oblimin rotation was used. The sum of examiner ratings was excluded because it was the only measure not performance‐based.ResultFor the oADAS, we identified two factors: A general factor (including 2 memory measures, naming, commands, and orientation) and a praxis factor (including constructional and ideational praxis). For the eADAS, we also identified two factors: A memory/speed factor (including 5 memory measures, orientation, word generation, and the letter‐digit test) and a general factor (including naming, constructional and ideational praxis, clock to command, and similarities). The commands subtest did not load onto either factor for the eADAS EFA. After controlling for education and sex, linear regression analysis confirmed previous findings that increasing age was associated with decreased factor scores (p < 0.001).ConclusionThe results of the present study provide novel information regarding the underlying factor structure of the oADAS and eADAS. Our results also confirm previous research demonstrating that increasing age is associated with reduced cognition after controlling for education and sex. Future directions include using these factor scores to examine the influence of risk factors for cognitive decline in predementia syndromes.

Effects of hearing intervention on cognitive decline: Results of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) randomized trial

AbstractBackgroundHearing loss is associated with greater cognitive decline and incident dementia. Whether hearing intervention could reduce cognitive decline in older adults with hearing loss is unknown.MethodThe ACHIEVE study is a randomized trial (NCT03243422) of 70‐84 year‐old adults with untreated hearing loss and free from substantial cognitive impairment that took place at four U.S. sites. Participants were recruited from two study populations: 1) a group of adults participating in a longstanding observational study of cardiovascular health (Atherosclerosis Risk in Communities [ARIC] study), and 2) a group of healthy de novo community volunteers. Participants were randomised (1:1) to hearing intervention (HI; audiological counseling and provision of hearing aids) or a successful aging health education control intervention (SA; sessions with a health educator on chronic disease prevention). The primary intention‐to‐treat endpoint was 3‐year change in a global cognition standardized factor score from a comprehensive neurocognitive battery.Result977 participants (238 ARIC, 739 de novo) underwent randomisation; 490 were assigned to HI and 487 to SA control. Participants from ARIC were older, had more risk factors for cognitive decline, and had lower baseline cognitive scores than the de novo group. In the primary analysis combining the ARIC and de novo groups, 3‐year cognitive change (in S.D. units) was not significantly different between HI and SA control (HI: ‐0·200 [95% CI: ‐0·256,‐0·144]; SA: ‐0·202 [‐0·258,‐0·145]; Difference 0·002 [‐0·077,0·081],p = 0·96). However, prespecified analyses demonstrated significant differences in the effect of HI on cognitive change between the ARIC and de novo group (p interaction = 0·010). In the ARIC group, HI was associated with a 48% reduction in 3‐year cognitive change compared to SA control (HI: ‐0·211 [‐0·349,‐0·073]; SA: ‐0·402 [‐0·536, ‐0·267]; Difference 0·191 [0·022,0·360,p = 0·027]). In the de novo group, cognitive change was not significantly different between HI and SA control (HI: ‐0·213 [‐0·277,‐0·148]; SA: ‐0·151 [‐0·215,‐0·087]; Difference ‐0·061 [‐0·151,0·028,p = 0·18]). The rate of cognitive change among control participants was observed to be 2.7‐fold faster in the ARIC versus de novo group.ConclusionHearing intervention may have a significant effect on reducing cognitive change over 3 years in populations of older adults at increased risk for cognitive decline.

Cognitive impairment and the blood-brain barrier in chronic kidney disease: role of the uremic toxins

Patients with chronic kidney disease (CKD) have an increased risk of cognitive disorders, presenting as vascular dementia, compared with the general population. These cognitive disorders occur early during the course of the kidney disease and evolve in parallel with the decline in glomerular filtration rate. They affect 30 to 80% of patients with stage 5 CKD. Kidney transplantation only partially improves cognitive impairment. In this narrative review, we summarize the epidemiology and recent clinical and experimental data on cognitive impairment in CKD and discuss the potential specific mechanisms. Among the factors associated with cognitive impairment, the accumulation of uremic toxins such as indoxyl sulfate appears to be a specific risk factor for cognitive decline. These toxins have an endothelial toxicity that can disrupt the cerebral endothelium. The rupture of the blood-brain barrier (BBB) is a mechanism implicated in several neurodegenerative pathologies and systemic diseases with cerebral tropism. Recent experimental findings in CKD indicate that disruption of the BBB appears to be an important mechanism behind cognitive impairment in CKD. In murine models of CKD, increased BBB permeability is linked to memory impairment and aryl hydrocarbon receptor activation following accumulation of circulating indoxyl sulfate. This disruption of the BBB could also have harmful consequences for stroke susceptibility and drug neurotoxicity in CKD patients.

Loneliness and cognitive function in older adults: Longitudinal analysis in 15 countries.

This study aims to evaluate the directionality of the association between loneliness and cognitive performance in older adults, accounting for confounding factors. Data were from 55,662 adults aged ≥ 50 years who participated in Waves 5-8 of the Survey of Health, Ageing and Retirement in Europe (SHARE). Loneliness was assessed with the Three-Item Loneliness Scale (TILS) and with a one-item direct question. Cognitive performance was assessed with four measures: verbal fluency, numeracy, immediate recall, and delayed recall. Age, sex, geographical area, educational attainment, partnership status, depressive symptoms, and previous chronic diseases at baseline were used as covariates. We analyzed the associations with three-wave random intercept cross-lagged panel models (RI-CLPM) and conducted age-stratified analysis among those younger versus older than 65 years. Full information maximum likelihood estimators were used to handle missing values in Waves 6-8 in the main analyses. We also conducted additional sensitivity analyses stratified by retirement status (retired vs. not) at baseline. At the within-person level, loneliness and cognitive performance were not associated with each other among those aged 50-64 years in the main time-lagged analysis. Among those aged ≥ 65 years, loneliness was associated with lower cognitive performance in the next wave in all four cognitive domains. In addition, lower verbal fluency predicted greater loneliness in the next waves among this age group. Similar patterns were found independently of retirement status at baseline. These results suggest that loneliness is a psychosocial risk factor for cognitive decline among older adults (≥ 65 years). (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Causal inference on strategies to increase conversational engagement for socially isolated older adults

AbstractBackgroundSocial isolation, characterized by a small social network and lack of contact, negatively impact the quality of life. Older adults are at an increased risk for social isolation, which is found to be a risk factor of cognitive decline and dementia. Enhancing social connectedness or interactions has been shown to be an effective intervention for slowing age‐associated cognitive decline and possibly delaying the onset of dementia. Here we aim to develop conversational chatbots which can provide engaging conversations with older adults with mild cognitive impairment (OAwMCI) to mitigate social isolation. To resemble human human interactions, chatbots have to adapt certain human strategies, such as empathy, during conversation.MethodOur study utilized causal structural learning and causal inference approaches to examine the dialogue strategy for engaging OAwMCI. We analyzed transcriptions from a clinical trial, I‐CONECT (ClinicalTrials.gov #: NCT02871921), which involved semi‐structured conversations between facilitators and participants. By using emotion recognition in conversation and dialogue act modeling, we produced a time series data of state (participant’s emotions and length of utterance per conversation turn), intervention (facilitator’s conversational strategies), and outcome (participant’s following emotions and engagement). A R package, pcalg, was used to identify causal relationships between the state, intervention, and outcome variables.ResultGraphical models implying causal relationships between certain factors were generated. Our analysis revealed that facilitators adjusted their dialogue strategies according to the participants' emotions and utterance. For example, facilitators expressed appreciation when a participant showed . Additionally, we found that the dialogue acts from facilitators influenced participants' emotions and engagement in the conversation. For instance, non‐opinion statements and yes/no questions from facilitators may affect participants’ verbal engagement and level of anger during the conversation.ConclusionFindings from this study are in line with real‐world human‐human conversation, and our next step is to explore how to use these findings to improve conversational chatbots. Future work shall also consider other crucial features into the state variable that might influence the dynamics of participants' status during the conversation, such as cognitive capacity and dialogue coherence. Our findings have the potential to inform the development of conversational tools and strategies to reduce social isolation among OAwMCI.

Are changes in muscular strength following head‐down bed rest independently associated with improved cognitive function in older adults? A secondary analysis of a randomized controlled trial

AbstractBackgroundPhysical inactivity is common among older adults and is a risk factor for cognitive decline. Even a brief period of physical inactivity, such as bed rest due to hospitalization, in older adults has significant negative impacts. Exercise is strategy to counter the negative effects of physical inactivity. Exercise‐induced improvements in cardiorespiratory fitness is associated with improved cognitive function. Less is known regarding the contribution of exercise‐induced changes in muscle strength to changes in cognitive function. Thus, we aimed to examine the independent contribution of: 1) change in cardiorespiratory fitness; and 2) change in peak muscle torque of the lower extremity to changes in cognitive function in a randomized controlled trial (RCT) of head‐down bed rest (HDBR) vs. HDBR with exercise in healthy older adults.MethodAn analysis of a non‐blinded, parallel‐group, RCT of 22 healthy older adults (11 males and 11 females) aged 55‐65 years. Participants were randomized to: 1) 14 days of 6° HDBR (CON); or 2) HDBR with daily resistance and aerobic exercise training (EX). Outcome measures were taken at baseline and HDBR completion. The Flanker Inhibitory Control and Attention Task measured executive function. Physical fitness measures included: 1) maximal aerobic capacity (VO2max) using a bicycle ergometry test; and 2) knee extension isokinetic muscular strength (KE) using a Biodex dynamometer. We performed two separate multiple linear regressions to determine whether following 14 days of HDBR: 1) VO2max was associated with Flanker score, after accounting for ΔKE; and 2) KE was associated with Flanker score, after accounting for ΔVO2max. Each model was also adjusted for baseline Flanker score and the baseline physical fitness measure of interest.ResultAt baseline, average Flanker t‐score was 48.33, mean VO2max was 32.527 ml/kg/min, and knee extension strength was 64.472 Nm. VO2max at follow‐up was not significantly associated with Flanker performance (b = 0.232 ± 0.716; p = 0.635; R2 adj. = 0.285). However, greater KE strength was significantly associated with better Flanker performance (b = 2.023 ± 0.389; p = 0.043; R2 adj. = 0.633) at HDBR completion.ConclusionThe maintenance of muscle strength even during brief periods of physical inactivity appears to be critical for cognitive health in older adults.

Late‐life hypertension acts together with amyloid‐β pathology to promote early cognitive decline

AbstractBackgroundMidlife hypertension (HTN) is a known risk factor for Alzheimer’s Disease (AD) development. However, whether the same effect is observed in older individuals, at risk for AD, remains to be elucidated. Here, we aimed to assess whether late‐life HTN and the presence of amyloid‐β pathology (Aβ) interact to promote longitudinal cognitive decline in cognitively unimpaired (CU) individuals, and if systolic blood pressure (SBP) levels moderate this interaction. Interactive effect of disease pathophysiology is crucial for dementia prevention strategies.MethodWe used two independent cohorts. We evaluated 475 CU individuals over 65 years of age from the ADNI cohort, with available baseline medical data and CSF Elecsys biomarkers (Aβ1‐42 and p‐tau181), as well as longitudinal clinical assessments with neuropsychological testing (up to 6 years); the individuals were classified as (A)+ or (A)‐ based on a previously proposed cut‐off of CSF p‐tau181/Aβ1‐42 lower than 0.025. We also evaluated 162 CU individuals over 65 years of age from the TRIAD cohort with baseline clinical data and Aβ‐PET, as well as longitudinal clinical assessments with neuropsychological testing (up to 3 years). The individuals were classified as (A)+ or (A)‐ based on Aβ‐PET positivity. All individuals were classified as positive or negative for hypertension based on medical history. For the ADNI cohort, we could also evaluate the SBP levels as a continuous variable.ResultLinear mixed‐effects (LME) models showed that HTN and Aβ acted together to promote longitudinal cognitive decline (ADNI: HTN X Aβ X Time, β = ‐0.44, p = 0.001, figure 1, TRIAD: HTN X Aβ X Time, β = ‐0.64, p < 0.001, figure 2). Also, we could see that higher SBP levels acted together with Aβ to promote further cognitive decline (SBP values X Aβ X Time, β = ‐0.011, p = 0.03, figure 3).ConclusionOur results support a framework in which late‐life HTN is a modifiable risk factor for cognitive decline in CU individuals at increased risk for AD. This supports further investigation in determining the best target of SBP levels for individuals at risk for AD, in the context of offering precision medicine for this population.

Socioeconomic position, modifiable dementia risk and cognitive decline: results of 12‐year Maastricht Aging Study

AbstractBackgroundEvidence of modifiable risk factors for cognitive decline and dementia is accumulating, showing the potential of dementia risk reduction via lifestyle modification and cardiovascular risk management. People with low socioeconomic status (SES) have increased dementia risk and on average worse health. This study investigated whether the association between a modifiable dementia risk score and rate of cognitive decline differs across SES strata.MethodData were used from Maastricht Aging Study (MAAS), a prospective cohort study with a 12‐year follow‐up. Participants aged ≥40 years with complete dementia risk profiles were included (n = 1223). The validated ’LIfestyle for BRAin health’ (LIBRA) index was used to assess the modifiable dementia risk fraction. Cognitive performance was serially assessed at baseline, 6 and 12 years and measured in the domains of information processing speed, executive functioning and verbal memory function. A SES compound score was calculated from equivalent income and educational level and divided into tertiles (low, middle, high). Linear mixed models were used to study the association between LIBRA, SES and their interaction on the rate of cognitive decline.ResultParticipants in the lowest SES tertile displayed more decline in information processing speed (vs. middle SES: X2 = 7.08, p = 0.029; vs. high SES: X2 = 9.49, p = 0.009) and verbal memory (vs. middle SES: X2 = 9.28, p<0.001; vs. high SES: X2 = 16.68, p<0.001) compared to their middle‐ and high‐SES counterparts. Higher (unhealthier) LIBRA scores were also associated with more decline in information processing speed (X2 = 12.66, p = 0.002) and verbal memory (X2 = 4.63, p = 0.032). No consistent effect modification by SES on the association between LIBRA and cognition was found.ConclusionThis study shows that lower SES and higher modifiable dementia risk predict faster decline in information processing speed and verbal memory function over 12 years. Results suggest that lifestyle is an important determinant of cognitive decline across SES groups. Yet, people with low SES had a more unfavourable modifiable risk score suggesting more potential for lifestyle‐based interventions. LIBRA could be useful as a participant selection tool or as a surrogate outcome measure in lifestyle intervention trials, and can inform people about individual risk behaviours as part of public health initiatives.

5 LIfestyle for BRAin Health (LIBRA) Modifiable Factors Risk Score and Concussion History Associations with Cognition in Older Former National Football League Players.

Objective:Traumatic brain injury is one of several recognized risk factors for cognitive decline and neurodegenerative disease. Currently, risk scores involving modifiable risk/protective factors for dementia have not incorporated head injury history as part of their overall weighted risk calculation. We investigated the association between the LIfestyle for BRAin Health (LIBRA) risk score with odds of mild cognitive impairment (MCI) diagnosis and cognitive function in older former National Football League (NFL) players, both with and without the influence of concussion history.Participants and Methods:Former NFL players, ages ≥ 50 (N=1050; mean age=61.1±5.4-years), completed a general health survey including self-reported medical history and ratings of function across several domains. LIBRA factors (weighted value) included cardiovascular disease (+1.0), hypertension (+1.6), hyperlipidemia (+1.4), diabetes (+1.3), kidney disease (+1.1), cigarette use history (+1.5), obesity (+1.6), depression (+2.1), social/cognitive activity (-3.2), physical inactivity (+1.1), low/moderate alcohol use (-1.0), healthy diet (-1.7). Within Group 1 (n=761), logistic regression models assessed the association of LIBRA scores and independent contribution of concussion history with the odds of MCI diagnosis. A modified-LIBRA score incorporated concussion history at the level planned contrasts showed significant associations across concussion history groups (0, 1-2, 3-5, 6-9, 10+). The weighted value for concussion history (+1.9) within the modified-LIBRA score was based on its proportional contribution to dementia relative to other LIBRA risk factors, as proposed by the 2020 Lancet Commission Report on Dementia Prevention. Associations of the modified-LIBRA score with odds of MCI and cognitive function were assessed via logistic and linear regression, respectively, in a subset of the sample (Group 2; n=289) who also completed the Brief Test of Adult Cognition by Telephone (BTACT). Race was included as a covariate in all models.Results:The median LIBRA score in the Group 1 was 1.6(IQR= -1, 3.6). Standard and modified-LIBRA median scores were 1.1(IQR= -1.3, 3.3) and 2(IQR= -0.4, 4.6), respectively, within Group 2. In Group 1, LIBRA score was significantly associated with odds of MCI diagnosis (odds ratio[95% confidence interval]=1.27[1.19, 1.28], p <.001). Concussion history provided additional information beyond LIBRA scores and was independently associated with odds of MCI; specifically, odds of MCI were higher among those with 6-9 (Odds Ratio[95% confidence interval]; OR=2.54[1.21, 5.32], p<.001), and 10+ (OR=4.55;[2.21, 9.36], p<.001) concussions, compared with those with no prior concussions. Within Group 2, the modified-LIBRA score was associated with higher odds of MCI (OR=1.61[1.15, 2.25]), and incrementally improved model information (0.04 increase in Nagelkerke R2) above standard LIBRA scores in the same model. Modified-LIBRA scores were inversely associated with BTACT Executive Function (B=-0.53[0.08], p=.002) and Episodic Memory scores (B=-0.53[0.08], p=.002).Conclusions:Numerous modifiable risk/protective factors for dementia are reported in former professional football players, but incorporating concussion history may aid the multifactorial appraisal of cognitive decline risk and identification of areas for prevention and intervention. Integration of multi-modal biomarkers will advance this person-centered, holistic approach toward dementia reduction, detection, and intervention.

6 Improved verbal fluency following unilateral right hemisphere subthalamic nucleus deep brain stimulation for Parkinson’s disease: Is implant hemisphere a modifiable risk factor for cognitive decline?

Objective:Non-motor symptoms, such as mild cognitive impairment and dementia, are an overwhelming cause of disability in Parkinson’s disease (PD). While subthalamic nucleus deep brain stimulation (STN DBS) is safe and effective for motor symptoms, declines in verbal fluency after bilateral DBS surgery have been widely replicated. However, little is known about cognitive outcomes following unilateral surgeries.Participants and Methods:We enrolled 31 PD patients who underwent unilateral STN-DBS in a randomized, cross-over, double-blind study (SUNDIAL Trial). Targets were chosen based on treatment of the most symptomatic side (n = 17 left hemisphere and 14 right hemisphere). All participants completed a neuropsychological battery (FAS/CFL, AVLT, DKEFS Color-Word Test) at baseline, then 2, 4, and 6 months post-surgery. Outcomes include raw scores for verbal fluency, immediate and delayed recall, and DKEFS Color-Word Inhibition trial (Trial 3) completion time. At 2, 4, and 6 months, the neurostimulation type (directional versus ring mode) was randomized for each participant. We compared baseline scores for all cognitive outcome measures using Welch’s two-sample t-tests and used linear mixed effects models to examine longitudinal effects of hemisphere and stimulation on cognition. This test battery was converted to a teleneuropsychology administration because of COVID-19 mid-study, and this was included as a covariate in all statistical models, along with years of education, baseline cognitive scores, and levodopa equivalent medication dose at each time point.Results:At baseline, patients who underwent left hemisphere implants scored lower on verbal fluency than right implants (t(20.66) = -2.49, p = 0.02). There were not significant differences between hemispheres in immediate recall (p = 0.57), delayed recall (p = 0.22), or response inhibition (p = 0.51). Post-operatively, left STN DBS patients experienced significant declines in verbal fluency over the study period (p = 0.02), while patients with right-sided stimulation demonstrated improvements (p < .001). There was no main effect of stimulation parameters (directional versus ring) on verbal fluency, memory, or inhibition, but there was a three-way interaction between time, stimulation parameters, and hemisphere on inhibition, such that left STN DBS patients receiving ring stimulation completed the inhibition trial faster (p = 0.035). After surgery, right STN DBS patients displayed faster inhibition times than patients with left implants (p = 0.015).Conclusions:Declines in verbal fluency after bilateral stimulation are the most commonly reported cognitive sequalae of DBS for movement disorders. Here we found group level declines in verbal fluency after unilateral left STN implants, but not right STN DBS up to 6 months after surgery. Patients with right hemisphere implants displayed improvements in verbal fluency. Compared to bilateral DBS, unilateral DBS surgery, particularly in the right hemisphere, is likely a modifiable risk factor for verbal fluency declines in patients with Parkinson’s disease.