Midlife Risk Factors Research Articles

Spatiotemporal Gait Characteristics and Neuropsychological Performance in Midlife

Abstract Background Midlife risk factors such as Type 2 Diabetes Mellitus (T2DM) confer a significantly increased risk of cognitive impairment in later life, with executive function, memory and attention domains often affected first. Spatiotemporal gait characteristics are increasingly recognised as biomarkers of neurocognitive function and later dementia risk. Methods Using an automated walkway, 24 spatiotemporal gait parameters were examined across 5 domains of gait previously linked to cognitive function on usual-pace, maximal-pace, and cognitive dual-task gait conditions. Neurocognitive function was measured using a neuropsychological assessment battery. Linear regression was used assess the relationship between each gait parameter across the three walks and cognitive function. Results 102 middle-aged adults underwent assessment, 65 with uncomplicated T2DM (57.5 ± 8.0 years; 40% female) and 37 healthy controls (57.0 ± 8.3 years; 62.1% female). T2DM was associated with significant changes in gait phases and rhythm domains at usual-pace, and greater gait variability observed during maximal-pace and dual-task. In the overall cohort, both gait pace and rhythm domains were associated with memory and executive function during usual pace walking. At maximal-pace, gait pace parameters were associated with reaction time and delayed memory. During the cognitive dual-task, associations between gait variability and delayed memory and executive function were observed. Associations persisted following covariate adjustment and did not differ by T2DM status. Conclusion This supports the use of spatiotemporal gait as an integrative biomarker of neurocognitive function in otherwise healthy middle-aged individuals. Discrete associations were seen between both differing gait tasks and gait domains with domain-specific neuropsychological performance. Employing both maximal-pace and dual-task paradigms, in addition to single-task usual-pace gait, may be important in cognitively unimpaired populations with risk factors for later cognitive decline - with the aim of identifying individuals who may benefit most from potential preventative interventions.

Latent profiles of modifiable dementia risk factors in later midlife: relationships with incident dementia, cognition, and neuroimaging outcomes.

In 2020, the Lancet Commission identified 12 modifiable factors that increase population-level dementia risk. It is unclear if these risk factors co-occur among individuals in a clinically meaningful way. Using latent class analysis, we identified profiles of modifiable dementia risk factors in dementia-free adults aged 60-64 years from the UK Biobank. We then estimated associations between these profiles with incident dementia, cognition, and neuroimaging outcomes, and explored the differences across profiles in the effects of a polygenic risk score for Alzheimer's disease on outcomes. In 55,333 males and 63,063 females, three sex-specific latent profiles were identified: cardiometabolic risk, substance use-related risk, and low risk. The cardiometabolic risk profile in both males and females was associated with greater incidence of all-cause dementia (male: OR [95% CI] = 2.33 [2.03, 2.66]; female: OR [95% CI] = 1.44 [1.24, 1.68]), poorer cognitive performance, greater brain atrophy, and greater white matter hyperintensity volume compared to the low risk profile. The substance use-related risk profile in males was associated with poorer cognitive performance and greater white matter hyperintensities compared to the low risk profile, but no difference in all-cause dementia incidence was observed (OR [95% CI] = 1.00 [0.95, 1.06]). In females, the substance use-related risk profile demonstrated increased dementia incidence (OR [95% CI] = 1.58 [1.57, 1.58]) and greater brain atrophy but smaller white matter hyperintensity volume compared to the low risk profile. The polygenic risk score had larger effects among females, and differentially influenced outcomes across profiles; for instance, there were larger effects of the polygenic risk score on atrophy in the cardiometabolic profile vs. the low risk profile among males, and larger effects of the polygenic risk score on loss of white matter integrity in the cardiometabolic profile vs. the low risk profile among females. These results reveal three modifiable dementia risk profiles, their unique cognitive/neuroimaging outcomes, and their interactions with genetic risk for Alzheimer's disease. These differences highlight the need to consider population heterogeneity in risk prediction tools and in planning personalized prevention strategies.

Changes in Alzheimer Disease Blood Biomarkers and Associations With Incident All-Cause Dementia

Plasma biomarkers show promise for identifying Alzheimer disease (AD) neuropathology and neurodegeneration, but additional examination among diverse populations and throughout the life course is needed. To assess temporal plasma biomarker changes and their association with all-cause dementia, overall and among subgroups of community-dwelling adults. In 1525 participants from the US-based Atherosclerosis Risk in Communities (ARIC) study, plasma biomarkers were measured using stored specimens collected in midlife (1993-1995, mean age 58.3 years) and late life (2011-2013, mean age 76.0 years; followed up to 2016-2019, mean age 80.7 years). Midlife risk factors (hypertension, diabetes, lipids, coronary heart disease, cigarette use, and physical activity) were assessed for their associations with change in plasma biomarkers over time. The associations of biomarkers with incident all-cause dementia were evaluated in a subpopulation (n = 1339) who were dementia-free in 2011-2013 and had biomarker measurements in 1993-1995 and 2011-2013. Plasma biomarkers of amyloid-β 42 to amyloid-β 40 (Aβ42:Aβ40) ratio, phosphorylated tau at threonine 181 (p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were measured using the Quanterix Simoa platform. Incident all-cause dementia was ascertained from January 1, 2012, through December 31, 2019, from neuropsychological assessments, semiannual participant or informant contact, and medical record surveillance. Among 1525 participants (mean age, 58.3 [SD, 5.1] years), 914 participants (59.9%) were women, and 394 participants (25.8%) were Black. A total of 252 participants (16.5%) developed dementia. Decreasing Aβ42:Aβ40 ratio and increasing p-tau181, NfL, and GFAP were observed from midlife to late life, with more rapid biomarker changes among participants carrying the apolipoprotein E epsilon 4 (APOEε4) allele. Midlife hypertension was associated with a 0.15-SD faster NfL increase and a 0.08-SD faster GFAP increase per decade; estimates for midlife diabetes were a 0.11-SD faster for NfL and 0.15-SD faster for GFAP. Only AD-specific biomarkers in midlife demonstrated long-term associations with late-life dementia (hazard ratio per SD lower Aβ42:Aβ40 ratio, 1.11; 95% CI, 1.02-1.21; per SD higher p-tau181, 1.15; 95% CI, 1.06-1.25). All plasma biomarkers in late life had statistically significant associations with late-life dementia, with NfL demonstrating the largest association (1.92; 95% CI, 1.72-2.14). Plasma biomarkers of AD neuropathology, neuronal injury, and astrogliosis increase with age and are associated with known dementia risk factors. AD-specific biomarkers' association with dementia starts in midlife whereas late-life measures of AD, neuronal injury, and astrogliosis biomarkers are all associated with dementia.

Discrete Relationships between Spatiotemporal Gait Characteristics and Domain-Specific Neuropsychological Performance in Midlife.

Midlife risk factors such as type 2 diabetes mellitus (T2DM) confer a significantly increased risk of cognitive impairment in later life with executive function, memory, and attention domains often affected first. Spatiotemporal gait characteristics are emerging as important integrative biomarkers of neurocognitive function and of later dementia risk. We examined 24 spatiotemporal gait parameters across five domains of gait previously linked to cognitive function on usual-pace, maximal-pace, and cognitive dual-task gait conditions in 102 middle-aged adults with (57.5 ± 8.0 years; 40% female) and without (57.0 ± 8.3 years; 62.1% female) T2DM. Neurocognitive function was measured using a neuropsychological assessment battery. T2DM was associated with significant changes in gait phases and rhythm domains at usual pace, and greater gait variability observed during maximal pace and dual tasks. In the overall cohort, both the gait pace and rhythm domains were associated with memory and executive function during usual pace. At maximal pace, gait pace parameters were associated with reaction time and delayed memory. During the cognitive dual task, associations between gait variability and both delayed memory/executive function were observed. Associations persisted following covariate adjustment and did not differ by T2DM status. Principal components analysis identified a consistent association of slower gait pace (step/stride length) and increased gait variability during maximal-pace walking with poorer memory and executive function performance. These data support the use of spatiotemporal gait as an integrative biomarker of neurocognitive function in otherwise healthy middle-aged individuals and reveal discrete associations between both differing gait tasks and gait domains with domain-specific neuropsychological performance. Employing both maximal-pace and dual-task paradigms may be important in cognitively unimpaired populations with risk factors for later cognitive decline-with the aim of identifying individuals who may benefit from potential preventative interventions.

Association of midlife air pollution exposures and residential road proximity with incident dementia: The Atherosclerosis Risk in Communities (ARIC) study

BackgroundIncreasing evidence links higher air pollution exposures to increased risk of cognitive impairment. While midlife risk factors are often most strongly linked to dementia risk, few studies have considered associations between midlife roadway proximity or ambient air pollution exposure and incident dementia decades later, in late life. ObjectivesOur objective was to determine if midlife exposures to ambient air pollution or roadway proximity are associated with increased risk of dementia in the Atherosclerosis Risk in Communities (ARIC) study over up to 29 years of follow-up. MethodsOur eligible sample included Black and White ARIC participants without dementia at Visit 2 (1990–1992). Participants were followed through Visit 7 (2018–2019), with dementia status and onset date defined based on formal dementia ascertainment at study visits, informant interviews, and surveillance efforts. We used adjusted Weibull survival models to assess the associations of midlife ambient air pollution and road proximity with incident dementia. ResultsThe median age at baseline (1990–1992, Visit 2) of the 12,700 eligible ARIC participants was 57.0 years; 56.0% were female, 24.2% were Black, and 78.9% had at least a high school education. Over up to 29 years of follow-up, 2511 (19.8%) persons developed dementia. No associations were found between ambient air pollutants and proximity to major roadways with risk of incident dementia. In exploratory analyses, living closer to roadways in midlife increased dementia risk in individuals younger at baseline and those without midlife hypertension, and there was evidence of increased risk of dementia with increased midlife exposure to NOx, several PM2.5 components, and trace metals among those with diabetes in midlife. ConclusionsMidlife exposure to ambient air pollution and midlife roadway proximity was not associated with dementia risk over decades of follow-up. Further investigation to explore potential for greater susceptibility among specific subgroups identified here is needed.

Forecasting the 20-Year Incidence of Dementia by Socioeconomic Status, Race/Ethnicity, and Region Based on Mid-Life Risk Factors in a U.S. Nationally Representative Sample.

Alzheimer's disease and related dementias (ADRD) incidence varies based on demographics, but mid-life risk factor contribution to this variability requires more research. The purpose of this study is to forecast the 20-year incidence of dementia in the U.S. overall and stratified by race/ethnicity, socioeconomic status (SES), and U.S. geographic region given prior mid-life risk factor prevalence and to examine the extent to which risk factor differences 20 years ago may explain current SES, race/ethnicity, or regional disparities in dementia incidence. We applied the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) prediction model to the 2006 wave of the Health and Retirement Study (HRS) in participants aged 45 to 64 to estimate the 20-year risk of incident ADRD. The 20-year risk of dementia among middle-aged Americans was 3.3% (95% CI: 3.2%, 3.4%). Dementia incidence was forecast to be 1.51 (95% CI: 1.32, 1.71) and 1.27 (95% CI: 1.14, 1.44) times that in Hispanic and Non-Hispanic Black individuals respectively compared statistically to Non-Hispanic White individuals given mid-life risk factors. There was a progressive increase in dementia risk from the lowest versus highest SES quintile. For geographic region, dementia incidence was forecast to be 1.17 (95% CI: 1.06, 1.30) and 1.27 (95% CI: 1.14, 1.43) times that in Midwestern and Southern individuals respectively compared statistically to Western individuals. Some disparities in dementia incidence could be explained by differences in mid-life risk factors and may point toward policy interventions designed to lessen the ADRD disease burden through early prevention.

Concussion burden and later-life cardiovascular risk factors in former professional American-style football players.

Mid-life cardiovascular risk factors are associated with later cognitive decline. Whether repetitive head injury among professional athletes impacts cardiovascular risk is unknown. We investigated associations between concussion burden and postcareer hypertension, high cholesterol, and diabetes among former professional American-style football (ASF) players. In a cross-sectional study of 4080 professional ASF players conducted between January 2015 and March 2022, we used an mulitsymptom concussion symptom score (CSS) and the number of loss-of-consciousness (LOC) episodes as a single severe symptom to quantify football-related concussion exposure. Primary outcomes were hypertension, dyslipidemia, and diabetes, defined by current or recommended prescription medication use. The prevalence of hypertension, high cholesterol, and diabetes among former players (52 ± 14 years of age) was 37%, 34%, and 9%. Concussion burden was significantly associated with hypertension (lowest vs. highest CSS quartile, odds ratio (OR) = 1.99; 95%CI: 1.33-2.98; p < 0.01) and high cholesterol (lowest vs. moderate CSS, OR = 1.46, 95%CI, 1.11-1.91; p < 0.01), but not diabetes. In fully adjusted models, the prevalence of multiple CVD was associated with CSS. These results were driven by younger former players (≤ 40 year of age) in which the odds of hypertension were over three times higher in those in the highest CSS quartile (OR = 3.29, 95%CI: 1.39-7.61; p = 0.01). Results were similar for LOC analyses. Prior concussion burden is associated with postcareer atherogenic cardiovascular risk profiles among former professional American football players.

Modifiable risk factors and risk of myocardial infarction in offspring with parental disease.

Children of patients with early-onset myocardial infarction (MI) are at increased risk, but the importance of concordant versus discordant parent-offspring risk factor profiles on MI risk is largely unknown. We quantified the long-term absolute risk of MI according to shared risk factors in adulthood. We sampled data on familial predisposed offspring and their parents from the Framingham Heart Study. Early MI was defined as a history of parental MI onset before age 55 in men or 65 in women. Individuals were matched 3:1 with non-predisposed offspring. Cardiovascular risk factors included obesity, smoking, hypertension, high cholesterol, and diabetes. We estimated the absolute 20-year incidence of MI using the Aalen-Johansen estimator. At age 40, the 20-year risk of MI varied by cholesterol level (high cholesterol 25.7% [95% confidence interval 11.2%; 40.2%] vs. non-high cholesterol 3.4% [0.5; 6.4]) among predisposed individuals and this difference was greater than in controls (high cholesterol 9.3% [1.5; 17.0] vs. non-high cholesterol 2.5% [1.1; 3.8]). Similar results were observed for prevalent hypertension (26.7% [10.8; 42.5] vs. 4.0% [0.9; 7.1] in predisposed vs. 10.8% [3.2; 18.3] and 2.1% [0.8; 3.4] in controls). Among offspring without risk factors, parental risk factors carried a residual impact on 20-year MI risk in offspring (0% [0; 11.6] for 0-1 parental risk factors versus 3.3% [0; 9.8] for ≥2 parent risk factors at age 40, versus 2.9% [0; 8.4] and 8.5% [0; 19.8] at age 50 years). Children of patients with early-onset MI have low absolute risks of MI in the absence of midlife cardiovascular risk factors, especially if the parent also had a low risk factor burden prior to MI.

Women with a history of gestational diabetes mellitus present an accumulation of cardiovascular risk factors at age 46-A birth cohort study.

The incidence of gestational diabetes mellitus (GDM) is globally increasing, and it has been associated with later type 2 diabetes, metabolic syndrome (MetS), and cardiovascular disease (CVD). However, long-term population-based studies investigating common CVD risk factors years after pregnancy are lacking. To evaluate the future mortality and morbidity in cardiovascular and metabolic diseases, we conducted a thorough investigation of midlife risk factors in women with and without previous GDM. A prospective population-based cohort study was conducted of 3173 parous women from the Northern Finland Birth Cohort, 1966. Study participants were obtained from the national register or patient records. Those with a GDM diagnosis formed the GDM cohort (n = 271), and those without a previous GDM diagnosis formed the control cohort (n = 2902). Clinical examinations were performed on participants at the age of 46 and included anthropometric measurements, oral glucose tolerance test (OGTT), biochemical measurements, and cardiovascular assessment. At the age of 46, women in the GDM cohort had a higher body mass index (BMI, 29.0 kg/m2 vs 26.3 kg/m2, p < 0.001) and greater waist circumference (94.1 cm vs 86.5 cm, p < 0.001) than the control cohort. In the GDM cohort, a higher incidence of impaired glucose tolerance (12.6% vs 7.3%, p = 0.002), more previously diagnosed and OGTT-detected type 2 diabetes (23.3% vs 3.9%, p < 0.001), lower high-density lipoprotein (1.53 mmol/L vs 1.67 mmol/L, p = 0.011), higher triglycerides (1.26 mmol/L vs 1.05 mmol/L, p = 0.002) and a higher fatty liver index (6.82 vs 2.47, p < 0.001), were observed even after adjusting for BMI, polycystic ovary syndrome, parity, level of education, physical activity, smoking, and alcohol consumption. The women in the GDM cohort also had more MetS (42.6% vs 21.9%, p < 0.001) and higher risk scores for CVD and fatal events (Framingham 4.95 vs 3.60, p < 0.001; FINRISK 1.71 vs 1.08, p < 0.001). Women with a previous diagnosis of GDM exhibit more risk factors for CVD in midlife and are at a higher risk for cardiovascular events later in life.

The PREVENT dementia programme: baseline demographic, lifestyle, imaging and cognitive data from a midlife cohort study investigating risk factors for dementia.

PREVENT is a multi-centre prospective cohort study in the UK and Ireland that aims to examine midlife risk factors for dementia and identify and describe the earliest indices of disease development. The PREVENT dementia programme is one of the original epidemiological initiatives targeting midlife as a critical window for intervention in neurodegenerative conditions. This paper provides an overview of the study protocol and presents the first summary results from the initial baseline data to describe the cohort. Participants in the PREVENT cohort provide demographic data, biological samples (blood, saliva, urine and optional cerebrospinal fluid), lifestyle and psychological questionnaires, undergo a comprehensive cognitive test battery and are imaged using multi-modal 3-T MRI scanning, with both structural and functional sequences. The PREVENT cohort governance structure is described, which includes a steering committee, a scientific advisory board and core patient and public involvement groups. A number of sub-studies that supplement the main PREVENT cohort are also described. The PREVENT cohort baseline data include 700 participants recruited between 2014 and 2020 across five sites in the UK and Ireland (Cambridge, Dublin, Edinburgh, London and Oxford). At baseline, participants had a mean age of 51.2 years (range 40-59, SD ± 5.47), with the majority female (n = 433, 61.9%). There was a near equal distribution of participants with and without a parental history of dementia (51.4% versus 48.6%) and a relatively high prevalence of APOEɛ4 carriers (n = 264, 38.0%). Participants were highly educated (16.7 ± 3.44 years of education), were mainly of European Ancestry (n = 672, 95.9%) and were cognitively healthy as measured by the Addenbrookes Cognitive Examination-III (total score 95.6 ± 4.06). Mean white matter hyperintensity volume at recruitment was 2.26 ± 2.77 ml (median = 1.39 ml), with hippocampal volume being 8.15 ± 0.79 ml. There was good representation of known dementia risk factors in the cohort. The PREVENT cohort offers a novel data set to explore midlife risk factors and early signs of neurodegenerative disease. Data are available open access at no cost via the Alzheimer's Disease Data Initiative platform and Dementia Platforms UK platform pending approval of the data access request from the PREVENT steering group committee.

Association between multimorbidity and cognitive decline in the elderly population of the Eastern Province, Saudi Arabia.

Cognitive decline affects the quality of life, and dementia affects independence in daily life activities. Multimorbidity in older adults is associated with a higher risk of cognitive impairment. This research aims to study the relationship between cognitive decline and multimorbidity in the elderly population in the Eastern Province, Saudi Arabia. This cross-sectional research was conducted from July to October 2022 among adults over 60 years. All patients with two or more comorbidities were contacted for a face-to-face interview and cognitive testing to estimate cognitive function by trained family physicians using St. Louis University Mental State Examination. ANOVA and Chi-square test were used to test for statistical significance. Binary logistic regression was used to show the odds of having cognitive impairment and multimorbidity. All tests were performed at 5% level of significance. The study involved 343 individuals; majority (74.1%) aged 60-75 years and were males (67.9%). Hypertension, diabetes, and chronic pain were reported by 56%, 48%, and 44% participants, respectively. Thirty percent participants had 3 or more comorbidities. About 36% had mild neurocognitive disorder and 31.2% had dementia. The results showed that age, gender (female), diabetes, stroke, chronic pain, and multimorbidity were significantly associated with cognitive impairment. In our study, hypertension, coronary artery diseases, depression, and anxiety were not significantly associated with risk of cognitive decline. Our study found that multimorbidity is significantly associated with cognitive decline. Controlling comorbidities and preventing risk factors in midlife could help in delaying the progression of the disease.

Abstract P253: Lifetime Risk of Dementia by Midlife Vascular Risk Factor Burden: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Vascular risk factors play an important role in the development of dementia and death over the lifecourse. However, no absolute lifetime risk of dementia by individual and composite number of vascular risk factors have been reported. Methods: We conducted a prospective cohort analysis of data from the Atherosclerosis Risk in Communities (ARIC) Study. We examined the associations of vascular risk factors with incident dementia. Risk factors were measured at visit 2 (1990-1992) and included hypertension (SBP140mmHg, DBP90mmHg or medication use), diabetes status (self-reported physician diagnosis, medication use or HbA1C6.5%) and smoking status. Incident dementia was ascertained via active surveillance involving cognitive function assessments, informant reports, hospitalization codes and death records. We performed survival analysis using age as time scale and accounted for death without dementia as a competing event. We used age 60 as the origin and age on December 31 st , 2019, as the administrative censoring endpoint. Results: Among 13,161 participants, 45%, 40%, and 15% had 0, 1 and 2+ risk factors. There was a dose-dependent association between number of risk factors and the cumulative incidence of dementia (Figure A) and death (Figure C) . In competing risk models ( Figure B ), the cumulative incidence of dementia (95% CI) in persons with 0, 1 and 2+ risk factors by age 80 was 7.5% (6.6-8.5%), 10.3% (9.2-11.5%) and 13.7% (11.5-15.7%). By age 90, due to higher risk of mortality among those with vascular risk factors, the dementia risk (95% CI) for 0, 1 and 2+ risk factors were 34.8 (32.3-37.3%), 31.2% (29.0-33.2%) and 26.7% (23.9-29.6%). Conclusion: Preventing vascular risk factors in midlife may substantially reduce the age-specific risk of dementia. However, since fewer risk factors also lead to longer survival to oldest ages where dementia risk is very high, reducing lifetime risk of dementia beyond age 90 years will require additional preventative strategies. Figure: Cumulative incidence of dementia using Kaplan Meier estimator (A), using cumulative incidence function with competing risk of death (B), and cumulative incidence of death (C), according to the number of vascular risk factors in mid-life.

Abstract 46: Midlife and Late-Life Population Attributable Fractions of Dementia Risk Factors in the United States: A Cohort Study From the Dementia Risk Pooling Project

Introduction: Dementia cases in the US are projected to nearly double from 5.3 million in 2019 to 10.5 million by 2050. Research has suggested that 41% of US dementia cases may be prevented by eliminating several specific modifiable risk factors. Still, few studies examine risk factor variation between midlife and late-life. Previous studies have also been limited by sample diversity and size. The Dementia Risk Pooling Project (DRPP) is a consortium of longitudinal cohorts including several underrepresented racial/ethnic groups pooled at the individual level. Methods: We estimated individual and combined population attributable fractions (PAF) for seven modifiable risk factors in midlife (aged 45-64) and late-life (aged 65+), using data from six US cohorts in DRPP. We also used potential impact fractions (PIF) to estimate dementia cases that could be prevented due to risk factor reduction in midlife and late-life based upon the National Alzheimer’s Advisory Council goal of a 15% reduction in dementia risk factors by 2030. Results: In a sample of 41,432 unique participants (ppts), risk factor exposure was measured in midlife for 29,983 ppts (60% female, 77% white) and in late-life for 30,633 ppts (56% female, 70% white). During follow-up, 4,186 midlife ppts and 4,893 late-life ppts developed dementia. We found that eliminating midlife risk factors could prevent a greater proportion of dementia cases [PAF 41.3%, 27.9%-54.6%] compared to late-life risk factors [23.1%, 12.4%-33.7%]. Midlife physical inactivity [18.8%, 15.1%-22.4%] appeared to be the greatest contributor. Late-life hypertension and depression appeared to contribute to 9.8% [5.5%-13.9%] and 4.2% [3.5%-5.0%] of cases, respectively. Given the US prevalence of dementia in 2020, we estimate that a 15% reduction in physical inactivity alone could prevent 148,339 dementia cases. Conclusion: The importance of modifiable risk factors for dementia may vary with age. These estimates could inform the timing of public health interventions for dementia prevention.

Cross-sectional associations between neighborhood characteristics, cognition and dementia risk factor burden in middle-aged and older Australians

Dementia disproportionately affects individuals from disadvantaged backgrounds, including those living in areas of lower neighborhood-level socioeconomic status. It is important to understand whether there are specific neighborhood characteristics associated with dementia risk factors and cognition which may inform dementia risk reduction interventions. We sought to examine whether greenspace, walkability, and crime associated with the cumulative burden of modifiable dementia risk factors and cognition. This was a cross-sectional analysis of 2016–2020 data from the Healthy Brain Project, a population-based cohort of community-dwelling individuals across Australia. Participants were aged 40–70 and free of dementia. Measures included greenspace (greenspace % in the local area, and distance to greenspace, n = 2,181); and intersection density (n = 1,159), and crime (rate of recorded offences; n = 1,159). Outcomes included a modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score to index the burden of modifiable vascular dementia risk factors; and composite scores of both memory and attention, derived from the Cogstate Brief Battery. Linear regressions adjusted for age, sex, education, and personal socio-economic status, demonstrated distance to greenspace (b ± SE per 2-fold increase = 0.09 ± 0.03, p =.005) and crime rate (b ± SE per 2-fold increase = 0.07 ± 0.03, p =.018) were associated with higher modified CAIDE. Higher crime was associated with lower memory performance (b ± SE = -0.03 ± 0.01, p =.018). The association between distance to greenspace and modified CAIDE was only present in low-moderate socioeconomic status neighborhoods (p interaction = 0.004). Dementia prevention programs that address modifiable risk factors in midlife should consider the possible role of neighborhood characteristics.

MIDLIFE MEDIATORS OF EDUCATIONAL DIFFERENCES IN DEMENTIA RISK IN LATER LIFE:PRELIMINARY RESULTS FROM THE HUNT STUDY

Abstract There is a well-known association between education and dementia risk. However, there is limited knowledge of the mediating mechanisms. Using data from the HUNT study linked with registries (n=9745), we examined the mediating role of occupation complexity, smoking, physical inactivity, systolic blood pressure, body mass index(BMI), cardiovascular diseases, hearing impairment, diabetes, and depression score (only in HUNT2) assessed during HUNT1(age 45years) and HUNT2(age 56years) for the association between education and dementia among 70+ years using causal mediation analysis. Among eligible participants, 15.7% had dementia at age 70+ years, completed compulsory education (25.7%), lower-secondary (41.7%), upper-secondary(12%), undergraduate(16.5%), and postgraduate education(4%). For every one-unit increase in educational level from compulsory education to the following levels, a decrease in the odds of having dementia among 70+ years was found (OR=0.74). Midlife mediators assessed at 45 and 56 years jointly explained 17.3% and 26.8% of the effect of education on dementia among 70+ years, respectively. Smoking and systolic blood pressure (each explained 3.7%) followed by BMI(explained 2.3%) showed a significant independent mediating role for the educational differences in dementia among 70+ years. Whereas, among the mediators assessed at the age of 56 years, systolic blood pressure(explained 6.1%), hearing impairment (explained 4.4%), smoking(explained 3.1%) and depression score(explained 2.7%) showed significant independent mediating effects. Midlife risk factors of dementia considered in this study explained nearly one-fourth of the effect of education on dementia in particular, systolic blood pressure, hearing impairment, smoking, depression score and BMI. If truly causal, these factors could indicate potential targets for interventions.

Profiles of modifiable dementia risk factors in later midlife: a latent class analysis

AbstractBackgroundIn 2020, the Lancet Commission identified 12 modifiable risk factors that may increase dementia risk at the population level. At the individual level, these risk factors may co‐occur; therefore, this study aimed to identify profiles of dementia risk factors in later midlife, and to explore differences in biological markers associated with those profiles.MethodsParticipants aged 60‐64 without dementia at baseline and who identified as Caucasian were identified from the UK Biobank. Data for each risk factor (education, hearing loss, traumatic brain injury, hypertension, alcohol consumption, obesity, smoking, depression, social isolation, physical inactivity, air pollution, and diabetes) were collected using a standardized clinical assessment or through linkage of inpatient records. Latent class analysis was performed to identify latent classes of individuals; missing data were handled using full information maximum likelihood. A multigroup analysis was used to consider differences by self‐reported sex. Associations between the classes and a panel of 29 blood biomarkers across six broad categories (hormonal, inflammatory, kidney, liver, lipids, and metabolic) were explored using the Bolck, Croon, and Hagenaars (BCH) method, considering sex and controlling for age; pairwise comparisons between classes were made using z‐tests.ResultsAmong n = 117,275 participants (males: n = 53,426, females: n = 63,849), a 4‐class solution was identified based on model fit statistics. Invariance testing revealed significantly different class solutions between sexes (Δχ2 = 11,615, Δdf = 52, p &lt; 0.001). In general, the following four groups were identified in both males and females: low risk, psychosocial risk, cardiometabolic risk, and risk related to substance use (Figure 1). These classes differed in their blood biomarkers in both males and females, with the greatest differences observed in females. Specifically, the largest differences were observed between the cardiometabolic risk class vs. other classes, and in biomarkers for inflammation and metabolism (e.g. c‐reactive protein, triglyceride:HDL cholesterol ratio).ConclusionIn both males and females in later midlife, four classes defined by modifiable dementia risk factors were identified. These profiles were associated with unique biomarker signatures. might further examine the effects of these risk factor profiles on dementia‐related pathophysiological changes.

Cardiovascular Disease and Alzheimer's Disease: The Heart-Brain Axis.

Cardiovascular disease (CVD) remains one of the leading causes of morbidity and mortality in aging adults across the United States. Prior studies indicate that the presence of atherosclerosis, the pathogenic basis of CVD, is linked with dementias. Alzheimer's disease (AD) and AD-related dementias are a major public health challenge in the United States. Recent studies indicate that ≈3.7 million Americans ≥65 years of age had clinical AD in 2017, with projected increases to 9.3 million by 2060. Treatment options for AD remain limited. Development of disease-modifying therapies are challenging due, in part, to the long preclinical window of AD. The preclinical incubation period of AD starts in midlife, providing a critical window for identification and optimization of AD risk factors. Studies link AD with CVD risk factors such as hypertension, inflammation, and dyslipidemia. Both AD and CVD are progressive diseases with decades-long development periods. CVD can clinically manifest several years earlier than AD, making CVD and its risk factors a potential predictor of future AD. The current review focuses on the state of literature on molecular and metabolic pathways modulating the heart-brain axis underlying the potential association of midlife CVD risk factors and their effect on AD and related dementias. Further, we explore potential CVD/dementia preventive strategies during the window of opportunity in midlife and the future of research in the field in the multiomics and novel biomarker use era.

Childhood Maltreatment and Dementia Risk Factors in Midlife: A Prospective Investigation.

Previous studies have linked childhood adversities to dementia risk, yet most studies are cross-sectional in design and utilize retrospective self-reports to assess childhood experiences. These design characteristics make it difficult to establish temporal order and draw firm conclusions. Using a longitudinal design, we sought to determine whether childhood maltreatment predicts dementia risk factors in middle adulthood. Data have been obtained from a prospective cohort design study of children with documented cases of childhood maltreatment (ages 0-11 years at case identification) and demographically matched controls who were followed up and interviewed in middle adulthood. Outcomes were assessed through a medical examination and interview, and 807 of the cases that included blood collection at mean age 41. Dementia risk were investigated using 11 potentially modifiable risk factors. Compared to controls, individuals with histories of childhood maltreatment had a higher risk of low educational attainment, low social contact, smoking, and clinical depression, and a higher total number of dementia risk factors. In general, childhood maltreatment predicted a higher risk of dementia for females, males, and Black and White participants. Black maltreated participants had a greater risk for traumatic brain injury compared to Black controls. Physical abuse, sexual abuse, and neglect, each predicted a higher number of dementia risk factors in mid-life. These findings provide evidence that childhood maltreatment increases the risk for dementia in mid-life and has a demonstrable impact lasting over 30 years. Reducing the prevalence of mid-life dementia risk factors could reduce the risk of later-life dementia.

New horizons in hearing conditions.

Hearing conditions such as hearing loss, tinnitus and hyperacusis are highly prevalent in the population and can severely impact communication and quality of life. Hearing is affected by multiple factors, including heredity, noise exposure, age, sex, ear disorders and lifestyle factors. Globally, hearing loss affects over 80% of adults aged 80years and older, is often experienced in combination with other long-term health conditions and is a mid-life risk factor for dementia. To form a themed collection, we searched Age and Ageing for articles on hearing conditions published from 2000 onwards. This resulted in 22 articles included within the collection. They examined a range of important topics related to hearing healthcare and research, including noise-induced hearing loss, health service quality and safety, psychological and psychosocial consequences of hearing loss and co-morbidities of hearing loss. All articles reported on hearing loss; there were no published articles with a primary focus on other hearing conditions such as tinnitus or hyperacusis, on the health of older people from the Deaf community or on users of Cochlear implants, suggesting key gaps in knowledge and targets for future research. This New Horizons article highlights novel directions in research and practice and takes a forward look at how research into hearing conditions may develop in years to come. It highlights opportunities for the growth of patient-centred research and hearing healthcare supported by the better integration of health and care services as well as cross-speciality working to include common co-morbid health conditions.

Knowledge and motivation to adopt recommended health behaviours to reduce dementia risk among the elderly in Norway: a qualitative study

ObjectivesDementia is a major healthcare challenge; however, there is evidence that modifiable risk factors may contribute to reduce dementia risk. The aim of the study was to explore the knowledge and motivation for adopting recommended health behaviours among older adults in Norway. Study designThe study has a qualitative, descriptive design. MethodsIndividual interviews were used for data collection. The study population comprised 15 participants, five men and 10 women, aged ≥73 years, recruited from a region in the centre of Norway. Interviews were analysed according to qualitative content analysis. ResultsThree categories were identified and presented as the main findings, as follows: (1) sufficient knowledge about risk reduction for dementia, including the media as the main source of information; (2) current prevention activities and motivation for risk reduction, including physical, social and cognitive activities and a healthy diet; and (3) motivation for prevention of dementia from a life-course perspective, including experience of health problems, desire to live independently and limited awareness of dementia risk factors in midlife. ConclusionsTo tailor information about the modifiable risk factors of dementia and develop preventive interventions, knowledge about motivating factors is essential. Promotion of healthy ageing is required in addition to addressing the fear of future illness and dependency.