Delayed Onset Of Dementia Research Articles

Relationship between social determinants of health and cognitive performance in an older American population: a cross-sectional NHANES study

ObjectiveThis study aims to investigate the influence of social determinants of health (SDoH) on cognitive performance.MethodsThis study surveyed a sample of older adults aged 60 years and older from the 2011–2014 cohort of participants in the U.S. National Health and Nutrition Examination Survey (NHANES). Data were collected during each survey cycle on self-reported domains of SDoH, which included eight subscales: employment, family income-to-poverty ratio, food security, education level, health insurance coverage, type of health insurance, home ownership, and marital status. Cognitive performance was evaluated using three tests: the Digit Symbol Substitution Test (DSST) for processing speed, the Animal Fluency Test (AFT) for executive function, and a subtest from the Coalition to Establish an Alzheimer’s Disease Registry (CERAD) for memory. Multifactorial linear regression modeling was employed to explore the association between SDoH and cognitive performance.ResultsA total of 2,819 elderly subjects were included in this study for analysis, with a mean age of 69.14 ± 0.19 years, 54.36% female and 45.64% male. The study found a negative association between the accumulation of unfavorable SDoH factors and cognitive performance. Similarly, certain unfavorable SDoH domains were negatively associated with cognitive performance.ConclusionThe findings suggest that unfavorable SDoH domains, particularly when unfavorable SDoH factors accumulate, are linked to decreased cognitive performance. Actively investigating the relationship between these factors may be a crucial strategy for delaying dementia onset.

Multi-domain Online Therapeutic Investigation Of Neurocognition (MOTION) - A randomized comparative-effectiveness study of two remotely delivered mind-body interventions for older adults with cognitive decline.

Research suggest that mind-body movement programs have beneficial effects on cognitive outcomes for older adults with cognitive decline. However, few studies have directly compared specific approaches to mind-body movement or studied the impact of remote program delivery. In a 3-arm randomized controlled trial (RCT) for older adults with cognitive impairment, we are comparing a multidomain mind-body program that emphasizes movement, body awareness, personal meaningfulness, and social connection, and a traditional Chinese mind-body exercise (Tai Chi) to a health and wellness education control condition. All 3 interventions are delivered remotely two times per week (onehour per session) for 12weeks. The two active interventions are live-streamed. Outcomes are assessed prior to, after, and 6-months after the interventions. The co-primary outcomes are changes on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) and brain functional connectivity in the Default Mode Network (DMN). Secondary outcomes include measures of specific cognitive domains (e.g., executive function, attention), mobility, and self-report measures of general well-being, quality of life, social engagement, self- and attention-regulation. This RCT will directly compare the effects of two mind-body movement programs versus an education control delivered remotely over 12weeks on cognitive, neuroimaging, and participant-reported outcomes. If successful, these programs may provide scalable strategies for slowing cognitive decline, which could potentially delay dementia onset in some individuals. NCT05217849.

Role of Meaningful Social Participation and Technology Use in Mitigating Loneliness and Cognitive Decline Among Older Adults.

Community social participation aids dementia prevention and alleviates loneliness among older adults. Incorporating occupational therapy using information and communications technology (ICT) could potentially delay dementia onset and reduce loneliness. To quantify how meaningful social participation, participation frequency, ICT use, and expanded social networks influence cognitive function and loneliness among socially active older Japanese adults. Cross-sectional exploratory study using structural equation modeling. Meetings organized by older adults at seven community gathering places in Osaka Prefecture, Japan. One hundred thirteen healthy older adult cohort members. Cognitive function assessed via Mini-Cog; loneliness assessed via the condensed UCLA Loneliness Scale. The final model demonstrated excellent fit, χ2(23) = 28.291, p = .205 (root mean square error of approximation = .045, 90% confidence interval [.000, .094]; confirmatory factor index = .995; Tucker-Lewis Index = .993). ICT use directly affected social networks (β = 0.472), which directly influenced participation frequency (β = 0.324) and meaningful social participation (β = 0.381). The indirect effect of meaningful participation significantly improved cognitive function (β = 0.237). The only indirect effect of meaningful interpersonal participation was a reduction in loneliness (β = -0.235). ICT use contributes to the expansion of social networks among elderly people. Furthermore, the frequency of social participation and the meaningfulness of such participation are related to reduction in loneliness and maintenance of cognitive function. Although the frequency of social participation was not directly related to these outcomes, the results suggest that meaningful social participation may play an important role in reducing loneliness and maintaining cognitive function. Plain-Language Summary: The promotion of social participation among older people is a global phenomenon, driven by the recognition of its positive relationship with cognitive function and the alleviation of loneliness. Nevertheless, older people's social participation is constrained by a combination of physical and social factors. To address this issue, there has been a push to promote social participation based on information and communications technology (ICT). However, no specific study has been conducted on occupational therapists' perspective in capturing social participation and the use of ICT. The findings of this study show that using ICT has the potential to enhance opportunities for social interaction for older adults, thereby improving the quality and quantity of social participation. The quality of social participation was identified as the sole factor that had a positive impact on cognitive function and loneliness. This study suggests the need for occupational therapists to consider means of facilitating the use of ICTs among older adults as well as interventions that use occupational therapy theory to enhance the meaningfulness of existing social participation opportunities.

The Influence of Birth Weight, Socio-Economic Status, and Adult Health on Brain Volumes during Ageing

Introduction: Greater late-life brain volumes are associated with resilience against dementia. We examined relationships between birth weight, lifelong socio-economic status, and health with late-life brain volumes. We hypothesised that early life factors directly affect late-life brain volumes. Methods: Adults aged 59–67 y underwent MRI and brain volumes were measured. Birth weight and lifelong health, and socio-economic status were quantified and the principal components of each extracted. Relationships were examined using regression and structural equation analysis. Results: Birth weight (β = 0.095, p = 0.017) and childhood socio-economic status (β = 0.091, p = 0.033, n = 280) were directly associated with brain volume. Childhood socio-economic status was further associated with grey matter volume (β = 0.04, p = 0.047). Adult health was linked to increased brain volume (β = 0.15, p = 0.003). Conclusion: Birth weight and childhood socio-economic status are associated with whole and regional brain volume through direct mechanisms. Optimal fetal development, reduced childhood poverty, and good adult health could reduce brain atrophy and delay dementia onset in late-life.

APOE ε4 carrier status moderates the effect of lifestyle factors on cognitive reserve.

This study examines the role of lifestyle factors in cognitive reserve among older adults, focusing on the moderating effect of apolipoprotein E (APOE) ε4 status. Data from 157 participants aged 45 and older from the Healthy Brain Initiative (HBI) were analyzed. Cognitive reserve was estimated using residual scores from Cognivue Clarity tests after accounting for brain atrophy and white matter hyperintensities (WMHs). Lifestyle factors included education, occupational attainment, physical activity, social engagement, diet, and mindfulness. Structural equation models were conducted to assess interactions. Significant interactions were found between APOE ε4 status and mindfulness and social engagement on cognitive reserve, indicating stronger associations for APOE ε4 carriers. APOE ε4 carriers may benefit more from certain lifestyle factors, potentially through stress reduction and anti-inflammatory pathways. These findings support integrating APOE ε4 genetic screening into personalized prevention strategies to enhance interventions aimed at preserving cognitive function and delaying dementia onset in at-risk populations. Mindfulness and social engagement have increased cognitive reserve in APOE ε4 carriers. Study uses residual scores from Cognivue Clarity tests to estimate cognitive reserve. APOE ε4 carriers show stronger associations with certain lifestyle factors on cognitive reserve. Personalized interventions could enhance cognitive resilience in genetically at-risk populations. Comprehensive assessment of multiple lifestyle factors highlights targeted intervention benefits.

Apathy, gait slowness, and executive dysfunction (AGED) triad: opportunities to predict and delay dementia onset.

This study investigates whether older adults diagnosed with the apathy, gait impairment, and executive dysfunction (AGED) triad, frequently associated with cerebrovascular disease and confounded with depression, have earlier dementia onset. We followed 322 community-dwelling older individuals (mean age 72.0 ± 6.4years; 58.3% women) free of dementia at baseline for up to 9years. The AGED triad was identified when gait slowness (< 1m/s), apathy (assessed by Geriatric Depression Scale-3A with ≥ 2 items), and executive dysfunction (assessed by the 75th percentile of Trail Making Test-part B by age range) were simultaneously present. Incident dementia was diagnosed using the clinical dementia rating scale. Over the 9-year follow-up (mean 45.1 ± 28.6months), 44 participants (13.6%) converted to dementia. Sixteen participants (5.0%) were diagnosed with AGED triad + and showed a significantly higher risk of earlier conversion to dementia compared with AGED triad- (hazard ratio = 5.08, 95%CI 2.16-11.97; p = 0.0001), as well as to those with only one AGED factor or fewer AGED factors. Hypertension and diabetes were 2 and 3 times more prevalent, respectively, in individuals with AGED triad + . These findings suggest that the AGED triad serves as a simplified and effective behavioral marker for accelerated progression to dementia.

Cardiometabolic and panvascular multimorbidity associated with motoric cognitive risk syndrome in older adults.

Motoric cognitive risk (MCR) syndrome as a pre-dementia syndrome often co-occurring with chronic health conditions. This study aims to investigate the prevalence of MCR and its association with cardiometabolic and panvascular multimorbidity among older people living in rural China. This population-based study included 1450 participants who were aged ≥ 60 years (66.2% women) and who undertook the second wave examination of the Confucius Hometown Aging Project in Shandong, China when information to define MCR was collected. Data were collected through in-person interviews, clinical examinations, and laboratory tests. Cardiometabolic and panvascular multimorbidity were defined following the international criteria. MCR was defined as subjective cognitive complaints and slow gait speed in individuals free of dementia and functional disability. Multivariable logistic regression models were used to examine the associations of MCR with multimorbidity. MCR was present in 6.3% of all participants, and the prevalence increased with advancing age. Cerebrovascular disease, ischemic heart disease, heart failure, and increased serum cystatin C were associated with increased likelihoods of MCR (multivariable-adjusted odds ratio range: 1.90-3.02, P < 0.05 for all). Furthermore, there was a dose-response relationship between the number of cardiometabolic diseases and panvascular diseases and the likelihood of MCR. The multivariable-adjusted odds ratio (95% CI) of MCR associated with cardiometabolic and panvascular multimorbidity were 2.47 (1.43-4.26) and 3.85 (2.29-6.47), respectively. Older adults with cardiometabolic and panvascular multimorbidity are at a higher likelihood of MCR. These findings may have implications for identifying older adults at pre-dementia state as targets for early preventive interventions to delay dementia onset.

Personal social network strengthens adherence to lifestyle changes in individuals with subjective cognitive decline.

Providing medical advice regarding lifestyle changes is currently the most effective intervention for delaying dementia onset among individuals with subjective cognitive decline (SCD). Adherence to such advice can be influenced by individual's social environment. We measured that impact within a Latinamerican population. We recruited 183 SCD individuals from a Memory Clinic, analyzed their health-related, and provided them with medical advice. We assessed personal network composition and its healthy habits. We evaluated adherence to medical advice 6 months later. The proportion of heavy drinkers in the network is a risk factor to reduce alcohol consumption (odds ratio [OR]=31.2, 95% confidence interval [CI] [3.73,301], p=0.002), poor diets in the network hinders improving diet (p<0.001 OR=74.1, 95% CI [14.7,471]), and sedentary people in the network make it difficult to start exercising (OR=4.92 95% CI [1.39,18.8], p=0.016). Personal networks have an inertial effect, as relationships engaged in an unhealthy habit lower the probability of individuals to quit that habit.

Evaluation of Mild Cognitive Impairment through Perientorhinal/Hippocampal Imaging and Comprehensive Neuropsychological and Psychophysical Assessment.

Mild cognitive impairment (MCI) is a significant concern as it is a risk factor for AD progression, and early detection is vital in order to delay dementia onset and enable potential therapeutic interventions. Olfactory impairment is recognized as a predictive biomarker in neurodegenerative processes. The aims of this study were to explore the degree of entorhinal cortical atrophy (ERICA) and the severity of MCI symptoms; to analyze magnetic resonance imaging (MRI) results for the entorhinal cortex, parahippocampal gyrus, peri entorhinal cortex, and the cerebellar tentorium; and to perform a comprehensive neuropsychological and psychophysical assessment. The main results highlighted that in our sample-multidomain amnesic MCI patients with hyposmic symptomatology-we found that ERICA scores were associated with the severity of anxiety symptomatology. One possible hypothesis to explain this observation is that anxiety may contribute to neurodegenerative processes by inducing chronic stress and inflammation. Future research should consider the longitudinal development of neuropsychological scores, anxiety disorders, and brain atrophy to determine their potential predictive value for MCI progression. These findings suggest the importance of psychological factors in MCI progression and the utility of neuropsychological assessment alongside neuroimaging techniques for early detection and follow-up in MCI patients.

Association of cognitive reserve with the risk of dementia in the UK Biobank: role of polygenic factors.

It remains unclear whether cognitive reserve can attenuate dementia risk among people with different genetic predispositions. We aimed to examine the association between cognitive reserve and dementia, and further to explore whether and to what extent cognitive reserve may modify the risk effect of genetic factors on dementia. Within the UK Biobank, 210 631 dementia-free participants aged ≥60 years were followed to detect incident dementia. Dementia was ascertained through medical and death records. A composite cognitive reserve indicator encompassing education, occupation and multiple cognitively loaded activities was created using latent class analysis, categorised as low, moderate and high level. Polygenic risk scores for Alzheimer's disease were constructed to evaluate genetic risk for dementia, categorised by tertiles (high, moderate and low). Data were analysed using Cox models and Laplace regression. In multi-adjusted Cox models, the hazard ratio (HR) of dementia was 0.66 (95% confidence interval (CI) 0.61-0.70) for high cognitive reserve compared with low cognitive reserve. In Laplace regression, participants with high cognitive reserve developed dementia 1.62 (95% CI 1.35-1.88) years later than those with low cognitive reserve. In stratified analysis by genetic risk, high cognitive reserve was related to more than 30% lower dementia risk compared with low cognitive reserve in each stratum. There was an additive interaction between low cognitive reserve and high genetic risk on dementia (attributable proportion 0.24, 95% CI 0.17-0.31). High cognitive reserve is associated with reduced risk of dementia and may delay dementia onset. Genetic risk for dementia may be mitigated by high cognitive reserve. Our findings underscore the importance of enhancing cognitive reserve in dementia prevention.

Developing the Healthy Actions and Lifestyles to Avoid Dementia or Hispanos y el ALTo a la Demencia program.

With Alzheimer's disease and related dementias (ADRD) representing an enormous public health challenge, there is a need to support individuals in learning about and addressing their modifiable risk factors (e.g., diet, sleep, and physical activity) to prevent or delay dementia onset. However, there is limited availability for evidence-informed tools that deliver both quality education and support for positive behavior change such as by increasing self-efficacy and personalizing goal setting. Tools that address the needs of Latino/a, at higher risk for ADRD, are even more scarce. We established a multidisciplinary team to develop the Healthy Actions and Lifestyles to Avoid Dementia or Hispanos y el ALTo a la Demencia (HALT-AD) program, a bilingual online personalized platform to educate and motivate participants to modify their risk factors for dementia. Grounded in social cognitive theory and following a cultural adaptation framework with guidance from a community advisory board, we developed HALT-AD iteratively through several cycles of rapid prototype development, user-centered evaluation through pilot testing and community feedback, and refinement. Using this iterative approach allowed for more than 100 improvements in the content, features, and design of HALT-AD to improve the program's usability and alignment with the interests and educational/behavior change support needs of its target audience. Illustrative examples of how pilot data and community feedback informed improvements are provided. Developing HALT-AD iteratively required learning through trial and error and flexibility in workflows, contrary to traditional program development methods that rely on rigid, pre-set requirements. In addition to efficacy trials, studies are needed to identify mechanisms for effective behavior change, which might be culturally specific. Flexible and personalized educational offerings are likely to be important in modifying risk trajectories in ADRD.

Association between blood pressure and dementia in older adults: a cross-sectional study from China.

The association between blood pressure (BP) and dementia in older adults remains unclear, prompting this study to investigate the relationship between various BP indicators and dementia in this population. A cross-sectional survey was conducted in 2019, including 3,599 participants aged 65 years or older. The basic demographic characteristics of participants were collected. BP measurements and neuropsychological assessments were performed. From the systolic BP (SBP) and diastolic BP (DBP) values, mean arterial pressure (MAP), pulse pressure (PP) and blood pressure index (BPI) were calculated. Generalized additive models and logistic regression models were used to analyze the association between BP indicators and dementia. Generalized additive models identified a U-shaped relationship between DBP and dementia, which was more significant in males and people 70 years of age and older. The optimal DBP associated with the lowest dementia risk was 85 mmHg. Logistic regression models revealed that compared to the DBP subgroup (80-89 mmHg), participants in the DBP < 80 mmHg subgroup and the DBP ≥100 mmHg subgroup had OR for dementia of 1.611 (95% CI: 1. 252-2.073, P < 0.001) and 1.423 (95% CI: 0.999-2.028, p = 0.050), respectively. A significant association was observed between BPI and dementia (OR:1.746 95% CI: 1.142-2.668, p = 0.010). In older adults, we found a U-shaped relationship between DBP and dementia, and a linear relationship between BPI and dementia. These results underscore the importance of considering DBP and BPI in BP management strategies for older adults to potentially prevent or delay dementia onset.

Adherence to cognitive and physical exercise engagement: a challenge to successful dementia risk reduction and prevention efforts.

With human life expectancy and proportion of older adults increasing, global use of evidence-supported preventative methods to minimize risk of brain-related disabilities such as Alzheimer's disease and other dementias-as well as interventions to slow rate of disease progression-is important. Sustained engagement in cognitive and physical exercise programs may prevent or delay dementia onset as well as maximize health and function of those with dementia. Despite awareness of the importance of cognitive and physical exercise to brain health, exercise program adherence by older adults is extremely challenging. In this Perspective article, we summarize what is known about contributors to exercise program adherence and strategies to promote it. We discuss our viewpoint on knowledge gaps regarding exercise adherence and research that needs to be conducted. We conclude by proposing a multi-dimensional exercise adherence assessment framework that includes portable neurophysiologic technologies to inform initial design and updating of individualized exercise programs that optimize sustained exercise program engagement and, ultimately, maximize brain health in older adults with and without mild cognitive impairment and dementia.

Effects of Exercise Alone or Combined With Cognitive Training and Vitamin D Supplementation to Improve Cognition in Adults With Mild Cognitive Impairment

Exercise, cognitive training, and vitamin D may enhance cognition in older adults with mild cognitive impairment (MCI). To determine whether aerobic-resistance exercises would improve cognition relative to an active control and if a multidomain intervention including exercises, computerized cognitive training, and vitamin D supplementation would show greater improvements than exercise alone. This randomized clinical trial (the SYNERGIC Study) was a multisite, double-masked, fractional factorial trial that evaluated the effects of aerobic-resistance exercise, computerized cognitive training, and vitamin D on cognition. Eligible participants were between ages 65 and 84 years with MCI enrolled from September 19, 2016, to April 7, 2020. Data were analyzed from February 2021 to December 2022. Participants were randomized to 5 study arms and treated for 20 weeks: arm 1 (multidomain intervention with exercise, cognitive training, and vitamin D), arm 2 (exercise, cognitive training, and placebo vitamin D), arm 3 (exercise, sham cognitive training, and vitamin D), arm 4 (exercise, sham cognitive training, and placebo vitamin D), and arm 5 (control group with balance-toning exercise, sham cognitive training, and placebo vitamin D). The vitamin D regimen was a 10 000 IU dose 3 times weekly. Primary outcomes were changes in ADAS-Cog-13 and Plus variant at 6 months. Among 175 randomized participants (mean [SD] age, 73.1 [6.6] years; 86 [49.1%] women), 144 (82%) completed the intervention and 133 (76%) completed the follow-up (month 12). At 6 months, all active arms (ie, arms 1 through 4) with aerobic-resistance exercise regardless of the addition of cognitive training or vitamin D, improved ADAS-Cog-13 when compared with control (mean difference, -1.79 points; 95% CI, -3.27 to -0.31 points; P = .02; d = 0.64). Compared with exercise alone (arms 3 and 4), exercise and cognitive training (arms 1 and 2) improved the ADAS-Cog-13 (mean difference, -1.45 points; 95% CI, -2.70 to -0.21 points; P = .02; d = 0.39). No significant improvement was found with vitamin D. Finally, the multidomain intervention (arm 1) improved the ADAS-Cog-13 score significantly compared with control (mean difference, -2.64 points; 95% CI, -4.42 to -0.80 points; P = .005; d = 0.71). Changes in ADAS-Cog-Plus were not significant. In this clinical trial, older adults with MCI receiving aerobic-resistance exercises with sequential computerized cognitive training significantly improved cognition, although some results were inconsistent. Vitamin D supplementation had no effect. Our findings suggest that this multidomain intervention may improve cognition and potentially delay dementia onset in MCI. ClinicalTrials.gov Identifier: NCT02808676.

Spectral power ratio as a measure of EEG changes in mild cognitive impairment due to Alzheimer’s disease: a case-control study

Adopting preventive strategies in individuals with subclinical Alzheimer’s disease (AD) has the potential to delay dementia onset and reduce healthcare costs. Thus, it is extremely important to identify inexpensive, scalable, sensitive, and specific markers to track disease progression. The electroencephalography spectral power ratio (SPR: the fast to slow spectral power ratio), a measure of the shift in power distribution from higher to lower frequencies, holds potential for aiding clinical practice. The SPR is altered in patients with AD, correlates with cognitive functions, and can be easily implemented in clinical settings. However, whether the SPR is sensitive to pathophysiological changes in the prodromal stage of AD is unclear. We explored the SPR of individuals diagnosed with amyloid-positive amnestic mild cognitive impairment (Aβ+aMCI) and its association with both cognitive function and amyloid load. The SPR was lower in Aβ+aMCI than in the cognitively unimpaired individuals and correlated with executive function scores but not with amyloid load. Hypothesis-generating analyses suggested that aMCI participants with a lower SPR had an increased probability of a positive amyloid positron emission tomography. Future research may explore the potential of this measure to classify aMCI individuals according to their AD biomarker status.

Cerebral Small Vessel Disease Progression and the Risk of Dementia: A 14-Year Follow-Up Study.

Cerebral small vessel disease (SVD) is considered the most important vascular contributor to cognitive decline and dementia, although a causal relation between its MRI markers and dementia still needs to be established. The authors investigated the relation between baseline SVD severity as well as SVD progression on MRI markers and incident dementia, by subtype, in individuals with sporadic SVD over a follow-up period of 14 years. The study included 503 participants with sporadic SVD, and without dementia, from the prospective Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study, with screening for baseline inclusion conducted in 2006. Follow-ups in 2011, 2015, and 2020 included cognitive assessments and MRI scans. Dementia was diagnosed according to DSM-5 criteria and stratified into Alzheimer's dementia and vascular dementia. Dementia as an endpoint was available for 498 participants (99.0%) and occurred in 108 participants (21.5%) (Alzheimer's dementia, N=38; vascular dementia, N=34; mixed-etiology Alzheimer's dementia/vascular dementia, N=26), with a median follow-up time of 13.2 years (interquartile range, 8.8-13.8). Higher baseline white matter hyperintensity (WMH) volume (hazard ratio=1.31 per 1-SD increase, 95% CI=1.02-1.67), presence of diffusion-weighted-imaging-positive lesions (hazard ratio=2.03, 95% CI=1.01-4.04), and higher peak width of skeletonized mean diffusivity (hazard ratio=1.24 per 1-SD increase, 95% CI=1.02-1.51) were independently associated with all-cause dementia and vascular dementia. WMH progression predicted incident all-cause dementia (hazard ratio=1.76 per 1-SD increase, 95% CI=1.18-2.63). Both baseline SVD severity and SVD progression were independently associated with an increase in risk of all-cause dementia over a follow-up of 14 years. The results suggest that SVD progression precedes dementia and may causally contribute to its development. Slowing SVD progression may delay dementia onset.

Ecological evidence for later dementia diagnosis in areas with higher rates of bilingualism: Evidence fromY Fro Gymraegin Wales

BackgroundBilingualism has been proposed as a protective factor against dementia, putatively delaying onset by several years. However, evidence is equivocal. One possibility is that the pattern of confounding varies across contexts, with confounders such as socioeconomic status, rurality, and migrant status being positively associated with bilingualism in some settings and negatively in others. The present study examines this in Welsh-speaking Wales, where the confounding structure differs from much of the literature.MethodsRoutine clinical data from the Memory Clinic service covering the counties of Gwynedd and Ynys Môn were used to examine the ecological correlation between Welsh-speaking rates and dementia diagnosis rates by lower super output area. Analyses were conducted using Poisson generalised linear mixed effects models with spatial auto-correlation terms.ResultsA total of 404 cases were identified. No overall association was observed between dementia diagnosis rates and Welsh-speaking rates, but the association was moderated by age band, such that Welsh-speaking rates were protective in 65–74 year-olds but a risk factor in 75+ year olds (rate ratio=.71, .53-.94). This was robust to adjustment for area-level poverty.ConclusionAlthough causation cannot be inferred, the findings are consistent with bilingualism delaying dementia onset. Welsh-English bilingualism provides a useful complement to research on this topic elsewhere in the world, as the confounding structure is unusual.

Identifying lifestyle factors that promote brain resilience in ApoE4 carriers

AbstractBackgroundApolipoprotein (ApoE) E4 (e4) carriers are at increased risk for Alzheimer’s disease (AD) (Strittmatter, 2012), which is often characterized by accelerated hippocampal atrophy and cognitive decline after 65 (Reinvang, 2013). However, not all e4 carriers develop AD. In those at heightened genetic risk, it is important to evaluate lifestyle factors that might slow brain aging, and delay dementia onset. Poorer sleep quality, physical activity, and diet have been associated with several AD‐related processes ‐ including increased beta‐amyloid burden, decline in vascular integrity, reduced glucose metabolism, and neuronal dysfunction (Mander 2017, Radak 2010, Sezgin 2014). Smoking (Durazzo, 2014) and excessive alcohol consumption (Venkataraman, 2017) have also been shown to promote AD pathology and risk. Moreover, social contact and education may enhance cognitive reserve (Livingston, 2020). Here, we investigated the role of these factors in promoting structural brain resilience in a population susceptible to AD from the UK Biobank (UKB; Miller, 2016).MethodUKB participants over age 65 with e3e4 or e4e4 genotype were included (1415M, 1355F). A novel deep learning method (Lam, 2020) was used to calculate predicted brain age (a machine‐learning estimate of a person’s age from their brain MRI). Participants were labeled as resilient if their predicted age was 3+ years younger than their actual age. Lifestyle factors evaluated may be found in Table 1. Association rule learning (Agrawal, 1993) using the mlxtend python library was used to identify sets of factors most often associated with resiliency.Result604/2770 of the e4 carriers were labeled as resilient (Figure 1). The antecedent set with the highest likelihood (42%) of being associated with resiliency included following the ideal recommendations for physical activity, infrequent alcohol consumption, averaging at least 7 hours of sleep/night, participating in leisure/social activities, and never having smoked. These measures also appeared in other likely antecedent sets (Table 2).ConclusionWe identified several lifestyle factors that may promote resilience to brain aging in those at elevated risk for AD. We aim to replicate our findings using a larger dataset with brain age calculated, and train sex‐specific models as well as testing them in people of more diverse ancestry.

Pathways explaining racial/ethnic and socio-economic disparities in incident all-cause dementia among older US adults across income groups

Differential racial and socioeconomic disparities in dementia incidence across income groups and their underlying mechanisms remain largely unknown. A retrospective cohort study examining all-cause dementia incidence across income groups was conducted linking third National Health and Nutrition Examination Surveys (NHANES III) to Centers for Medicare and Medicaid Services-Medicare data over ≤26 y of follow-up (1988–2014). Cox regression and generalized structural equations models (GSEM) were constructed among adults aged≥60 y at baseline (N = 4,592). Non-Hispanic Black versus White (NHW) adults had higher risk of dementia in age and sex-adjusted Cox regression models (HR = 1.34, 95%CI: 1.15–1.55, P < 0.001), an association that was attenuated in the SES-adjusted model (HR = 1.15, 95%CI: 1.01–1.34, P = 0.092). SES was inversely related to dementia risk overall (per Standard Deviation, HR = 0.80, 95% CI:0.69–0.92, P = 0.002, Model 2), mainly within the middle-income group. Within the lowest and middle-income groups and in socio-economic status (SES)-adjusted models, Mexican American participants were at lower all-cause dementia risk compared with their NHW counterparts. GSEM models further detected 3 pathways explaining >55% of the total effect of SES on dementia risk (Total effect = −0.160 ± 0.067, p = 0.022), namely SES→LIFESTYLE→DEMENTIA (Indirect effect (IE) = −0.041 ± 0.014, p = 0.004), SES→LIFESTYLE→COGN→DEMENTIA (IE = −0.006 ± 0.001, p < 0.001), SES→COGN→DEMENTIA(IE = −0.040 ± 0.008, p < 0.001), with the last two remaining significant or marginally significant in the uppermost income groups. Diet and social support were among key lifestyle factors involved in socio-economic disparities in dementia incidence. We provide evidence for modifiable risk factors that may delay dementia onset differentially across poverty-income ratio groups, underscoring their importance for future observational and intervention studies.

Fluctuation of depressive symptoms in cognitively unimpaired participants and the risk of mild cognitive impairment 5 years later: Results of the Heinz Nixdorf Recall study.

Depression might be an independent risk factor for cognitive decline, a prodromal dementia symptom or a reaction to cognitive/functional impairment. To investigate the association between (1) depressive symptoms and (2) depressive symptom patterns over 13 years with incident mild cognitive impairment (MCI) 5 years later. We included 724/823 cognitively unimpaired men/women who participated in the population-based Heinz Nixdorf Recall study (t1: 2005-2008, ø62.9 years; t2: 2010-2015, ø68.1 years). Depressive symptoms were assessed in the study center and during six postal follow-ups using the short form of the Center for Epidemiologic Studies Depression Scale (CES-D). Relative risks (RR; 95% confidence intervals) for MCI at t2 (men/women: 71/76) were estimated for CES-D at t1 (linear and dichotomized at ≥17, cut-off for clinically relevant depressive symptoms) and CES-D fluctuations over 13 years (stable low, large fluctuations, stable high/stable around cut-off) using log-linear regression models with Poisson working likelihood adjusted for age, sex, education, diabetes mellitus, coronary heart disease, and stroke. Fully adjusted risk for MCI at t2 (per CES-D point increase at t1) was elevated for the total cohort (1.053, 1.031-1.076), men (1.046, 1.012-1.081), and women (1.059, 1.029-1.090). Applying the dichotomized CES-D, risk for MCI was substantially increased for the total cohort [2.22 (1.38-3.58)] and in women [2.59 (1.46-4.58)]. Large CES-D fluctuations and stable high/stable around cut-off were associated with increased RR for MCI in the total cohort and in women compared to stable low symptoms. Depressive symptoms predicted MCI in cognitively unimpaired participants of our population-based study. Adequate treatment of depression may therefore contribute to the maintenance of normal cognition and delay dementia onset.