Abstract Mobility impairment is a geriatric giant. Particularly, slow gait is associated with elevated risk for cognitive decline, disabilities and dementia. Gait is the product of complex neural network interactions and changes in their connectivity pattern may negatively impact gait speed. However, mechanistic neural correlates for gait speed maintenance and decline remained unclear. As such, the aim of this study is to investigate differences in neural network connectivity in older adults with and without gait speed decline over 24 months. This sub-analysis included 35 community-dwelling older adults age >70 years from the MOBILIZE Boston Study. Baseline assessments included four-meter gait speed test and resting-state fMRI. Gait speed was reassessed at a 24-month follow-up. Participants were stratified to “Maintainer” and “Decliner” groups based upon a cut-off of >0.05 m/s decline in gait speed from baseline to follow-up. A priori selected functional network included sensori-motor network (SMN) and frontoparietal network (FPN). Multivariate analysis of variance was performed to determine between group differences in network connectivity. Discriminant analysis was conducted to identify relative contribution of network connectivity to group classification. Between the 14 Maintainers and 21 Decliners (mean age 83.9 years), Maintainers were younger (p=0.088). After adjusting for age, Maintainers exhibited lower SMN premotor-precentral gyrus connectivity (p=0.023), greater FPN ventral visual-supramarginal gyrus connectivity (p=0.025), and trend level greater SMN-FPN cerebellum-occipital connectivity (p=0.053). Premotor-precentral gyrus connectivity showed greatest contribution to discriminant function. These preliminary findings suggest aberrant connectivity patterns of the SMN and FPN may be predictive of older adults’ ability to maintain gait speed.

Background

Pain is associated with cognitive decline among older adults, but few studies have investigated bidirectional associations between pain and cognitive decline, especially in older Hispanic populations. Our objective was to assess the bidirectional association between pain interference and cognitive performance in a sample of older Puerto Rican adults.

Methods

Data came from baseline and 4-year follow-up of the Puerto Rican Elderly: Health Conditions Study, a longitudinal representative study of Puerto Rican older adults aged 60 and older. Pain and cognitive performance were assessed at each wave. A pain interference variable was created using the sum of pain status (yes/no) and pain interference (yes/no; range 0-2). Global cognitive performance was assessed with the Mini-Mental Cabán. We tested bidirectional associations using a path model with concurrent and cross-lagged paths between pain and cognitive performance, adjusting for sociodemographic and health factors (n = 2 349).

Results

Baseline pain interference was not associated with baseline cognitive performance (p = .636) or with cognitive performance at follow-up (p = .594). However, increased pain interference at follow-up was associated with greater cognitive decline at follow-up (β = -0.07, standard error [SE] = 0.02, p = .003). Greater baseline cognitive performance was associated with lower pain interference at follow-up (β = -0.07, SE = 0.02, p = .007).

Conclusions

These findings highlight the importance of worsening pain interference as a potentially modifiable risk factor for cognitive decline, as pain treatment options exist. Additionally, better baseline cognitive performance may be a protective factor for pain, providing further evidence of the dynamic relationship between pain and cognitive performance.

Background

Studies have demonstrated women to have a higher prevalence of dementia compared to men. However, sex differences in dementia incidence are controversial with conflicting reports showing women with higher, lower, or similar incidence. Source of difference may be due to clinical setting and lack of consideration of competing risk of death. We examined dementia incidence in a sample of the national Veteran population to determine differences by sex.

Methods

We examined data from the Veterans Health Administration (VHA), the largest integrated health care system in the United States. We studied 947 797 Veterans aged ≥55 years (mean age: 69.9 ± 8.4, 3% female) evaluated in the VHA from October 1, 1999 to September 30, 2019. We estimated age-adjusted incidence rates of dementia (International Classification of Diseases, 9th and 10th Edition codes) by sex, and used Fine-Gray proportional hazards models with age as time scale to examine time to diagnosis, accounting for competing risk of death.

Results

During the follow-up (mean 8.4 years), 11.3% (n = 106 977, 11.4% men and 8.0% women) of Veterans developed dementia. Age-adjusted incidence was 12.6/1 000 person-years for men and 12.7/1 000 person-years for women. Compared to male Veterans, risk dementia was slightly higher among females (hazard ratio = 1.15; 95% confidence interval: 1.10-1.20), and on average, female Veterans developed dementia 0.2 years earlier than male Veterans. After additional adjustment for race, education, medical, and psychiatric conditions, results were similar.

Conclusions

Among older Veterans in a national cohort, women had a slightly increased risk for developing dementia compared to men after accounting for competing risk of death.

Background

The existing literature suggests that impaired olfaction may be an early marker for cognitive decline. Tracking the earliest stages of the progression to dementia is paramount, and yet the importance of olfactory ability throughout cognitive states and death remains unclear.

Methods

Drawing data from the Rush Memory and Aging Project (N = 1 501; 74% female), olfactory ability was assessed using the Brief Smell Identification Test (range = 0-16), while cognitive states (unimpaired, mild cognitive impairment [MCI], and dementia) were determined using a 3-step neuropsychological diagnostic protocol at up to 15 annual occasions. Multistate survival models simultaneously estimated the association of olfactory ability on transitions through cognitive states and death, while multinomial regression models estimated cognitively unimpaired and total life expectancies.

Results

Higher olfactory scores were associated with a reduced risk of transitioning from unimpaired cognition to MCI (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.82-0.88) and from MCI to dementia (HR = 0.89, 95% CI = 0.86-0.93), indicating that 1-unit increase in olfactory scores was associated with an approximate 14% and 11% reduction in risk, respectively. Additionally, higher olfactory scores were associated with a greater likelihood of transitioning backward from MCI to unimpaired cognition (HR = 1.07, 95% CI = 1.02-1.12). Furthermore, higher baseline olfactory scores were associated with more years of longevity without cognitive impairment. However, olfaction was not associated with the transition to death when accounting for transitions through cognitive states.

Conclusions

Findings suggest that higher olfactory identification scores are associated with a decreased risk of transitioning to impaired cognitive states and that associations between olfaction and mortality may occur primarily through the pathway of neurodegeneration.

Background

Older females show greater cognitive gains from physical activity (PA) than males, which may be related to long-term consequences of female-specific reproductive events (eg, pregnancy) on cognitive health.

Methods

To determine whether previous parity could moderate the relationship between PA and cognitive decline in older women, we conducted secondary analyses of data from the Health, Aging, and Body Composition Study. We tested whether the association between average PA over 10 years and cognition (Modified Mini-Mental State Examination [3MS]) and executive functioning (digit symbol substitution test [DSST]) over 10 years varied by previous parity (nulliparity, low parity, medium parity, and grand multiparity). An analysis of covariance was performed with cognition (average and change over 10 years) as the dependent variables, parity as a categorical predictor, average PA as a continuous predictor, and a set of relevant covariates.

Results

Significant interactions were found between PA and parity group for all 4 comparisons: average 3MS (p = .014), average DSST (p = .032), change in 3MS (p = .016), and change in DSST (p = .017). Simple slope analyses indicated the positive relationship between PA and average 3MS and DSST was only significant in the nulliparity and grand multiparity groups, and the positive relationship between PA and change in 3MS and DSST was only significant in the grand multiparity group.

Conclusion

The findings suggest the relationship between self-reported walking and cognitive performance was strongest in the groups at risk for cognitive decline and dementia, the nulliparous and grand multiparous groups.

Both education and cardiovascular risk factors are strongly associated with dementia risk. However, it is not clear whether these associations persist or vary among individuals with high genetic risk for Alzheimer's disease. We examined the interactive relationship between lifestyle and genetic dementia risk factors in a prospective cohort study. Our data came from the Atherosclerosis Risk in Communities study participants (n = 13 715; baseline age 45-64; 25% Black; 55% female), who were followed for incident dementia from 1987 through 2017. We used Cox proportional hazard models to estimate the risk of dementia (ascertained through in-person examination, telephone cognitive screeners, and/or hospital and death records) associated with baseline education and cardiovascular risk factors (measured using the American Heart Association's "Life Simple 7") among ε4 carriers and non-carriers separately. We also examined differences by race and sex. Two thousand two hundred and twenty-six incident dementia cases occurred over a median 25 years of follow-up. Lower educational attainment and poorer cardiovascular health were associated with greater risk of incident dementia. There was an education by apolipoprotein E (APOE) status interaction (p = .005) whereby the association of education and dementia was weaker for ε4 carriers (HR college graduates vs less than high school: 0.71 [0.59-0.84] than non-carriers (0.54 [0.47-0.63]). There was no interaction between APOE status and cardiovascular health on dementia risk. These relationships did not vary significantly by race or sex. Education and cardiovascular health were associated with lower dementia risk regardless of APOE genotype, though the protective effects of education were somewhat diminished among ε4 carriers.

Background

Musculoskeletal pain, a possible marker of central sensitization, is associated with higher prevalence of lower urinary tract symptoms (LUTS) among older men. We investigated whether musculoskeletal pain is associated with LUTS progression.

Methods

Participants were 5 569 men age ≥65 years enrolled in the prospective, multicenter Osteoporotic Fractures in Men (MrOS) Study. Self-reported musculoskeletal pain within 12 months before baseline was categorized as any pain and multilocation pain. Pain interference within 4 weeks of baseline was assessed with the SF-12 questionnaire. LUTS were assessed repeatedly with the American Urological Association Symptom Index (AUA-SI). Men with severe LUTS at baseline were excluded. LUTS progression was defined as the first occurrence of a ≥4-point AUA-SI increase during a 2-year follow-up interval. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using multivariable pooled logistic regression.

Results

LUTS progression was 37% higher among men with any musculoskeletal pain compared with men without pain (IRR 1.37, 95% CI: 1.21, 1.54). Positive associations were also observed between LUTS progression and pain at 1 (IRR 1.31, 95% CI: 1.13, 1.48) and ≥2 locations (IRR 1.42, 95% CI: 1.24, 1.60). Compared with men without pain interference, men with quite a bit/extreme pain interference were most likely to experience LUTS progression (minimal interference IRR 1.15, 95% CI: 1.03, 1.26; moderate interference IRR 1.28, 95% CI: 1.11, 1.45; quite a bit/extreme interference IRR 1.47, 95% CI: 1.22, 1.71).

Conclusions

Among men initially without severe LUTS, musculoskeletal pain is associated with an increased risk of LUTS progression. Studies using validated measures of central sensitization and LUTS progression among men are warranted.

Background

Adiposity increases risk for male lower urinary tract symptoms (LUTS), although longitudinal studies have produced conflicting results. No prior studies have evaluated longitudinal associations of changes in adiposity with concurrent LUTS severity among older men.

Methods

We used repeated adiposity measurements from dual-energy x-ray absorptiometry (DXA), body mass index (BMI), and American Urological Association Symptom Index (AUASI) measured at 4 study visits over a 9-year period among 5 949 men enrolled in the Osteoporotic Fractures in Men (MrOS) study. Linear mixed effect models adjusted for age, health-related behaviors, and comorbidities were created to evaluate the association between baseline and change in visceral adipose tissue (VAT) area, total fat mass, and BMI with change in LUTS severity measured by the AUASI.

Results

A nonlinear association was observed between baseline VAT area and change in AUASI: men in baseline VAT tertile (T) 2 had a lower annual increase in AUASI score compared to men in T1 and T3 (T2 vs T1: β = -0.07; 95% CI -0.12, -0.03; p = .008; T3 vs T1: NS) but differences were small. No significant associations were observed between change in VAT area and change in AUASI score. Neither baseline tertiles nor change in total fat mass or BMI were associated with change in AUASI score.

Conclusions

Changes in VAT area, total fat mass, and BMI were not associated with change in LUTS severity in this cohort. Thus, despite other health benefits, interventions targeting adiposity alone are unlikely to be effective for preventing or treating LUTS among older men.

Background

Muscle mass declines with age, while body adiposity increases. Sarcopenic obesity has been proposed to be particularly deleterious. However, previous methods for estimating muscle mass have been inadequate, and the relative contributions of total body fat versus muscle fat to adverse outcomes have been unclear.

Method

In a large cohort of older men (N = 1 017), we measured muscle mass (D3-creatine dilution), muscle density (high-resolution peripheral quantitative computed tomography in the diaphyseal tibia) as a proxy of muscle fat, and total body fat (dual-energy x-ray absorptiometry). We examined their associations with physical performance (walking speed, grip strength, chair stand time), the risk of mobility outcomes (mobility limitations, mobility disability), and the risk of death over ~5 years.

Results

In combined models, lower muscle mass and muscle density were independently associated with worse physical performance and the risk of adverse outcomes, while total body fat was minimally related to physical performance and not related to mobility outcomes or mortality. For example, the relative risks for mortality per 1 standardized unit increase in muscle density, muscle mass, and total body fat were 0.84 (95% confidence interval: 0.74, 0.96), 0.70 (0.57, 0.86), and 0.90 (0.64, 1.25), respectively.

Conclusions

Muscle mass and muscle density were associated with physical performance and adverse outcomes, and had independent, additive effects. There was little additional contribution of total body fat.

Background

Lower physical activity (PA) is associated with greater perceived fatigability, a person-centered outcome. The association between change in PA and fatigability with advanced age has yet to be established.

Methods

Community-dwelling older men (N = 1 113, age = 84.1 ± 3.9 years at Year 14) had free-living PA assessed using SenseWear Armband prospectively at Year 7 (2007-2009) and Year 14 (2014-2016) of Osteoporotic Fractures in Men Study, a longitudinal cohort established in 2000 (baseline). We categorized percent changes in PA into groups (large decline → large increase) for 4 metrics: step count, light intensity PA (LIPA, metabolic equivalents [METs] >1.5 to <3.0), moderate-to-vigorous PA (MVPA, METs ≥ 3.0), and sedentary behavior (SB, METs ≤ 1.5, excluding sleep). Perceived physical and mental fatigability were measured (Year 14) with the Pittsburgh Fatigability Scale (PFS, higher score = greater fatigability; range = 0-50). Associations between each metric of percent changes in PA and fatigability were examined using linear regression, adjusted for demographics, change in health conditions, and Year 7 step count or total PA (METs > 1.5).

Results

Men declined 2 336 ± 2 546 (34%) steps/d, 24 ± 31 (25%) LIPA min/d, 33 ± 58 (19%) MVPA min/d, and increased 40 ± 107 (6%) SB min/d over 7.2 ± 0.7 years. Compared to large decline (% change less than -50%), those that maintained or increased step count had 3-8 points lower PFS Physical scores; those who maintained or increased LIPA and MVPA had 2-3 and 2-4 points lower PFS Physical scores, respectively (all p ≤ .01). Associations were similar, but smaller, for PFS Mental scores.

Conclusion

Older men who maintained or increased PA had lower fatigability, independent of initial PA. Our findings inform the types and doses of PA that should be targeted to reduce fatigability in older adults.