Background

This study aimed to assess the associations of orthostatic hypotension (OH), in the presence or absence of frailty, with dementia and mortality in older adults.

Methods

We conducted a 15-year population-based cohort study including 2 703 baseline dementia-free individuals from the Swedish National Study on Aging and Care in Kungsholmen. At baseline, OH was defined as a decline in systolic/diastolic blood pressure ≥20/10 mm Hg 1 minute after standing up from a supine position. Frailty status was defined following Fried's frailty phenotype. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders-fourth edition criteria. Multistate flexible parametric survival models were used to estimate associations of OH and frailty with dementia and mortality.

Results

Robust people with OH (adjusted hazard ratio [HR] = 2.28; 95% confidence interval [CI] = 1.47-3.54) and frail people without OH (HR = 1.98; 95% CI = 1.40-2.82) or with OH (HR = 2.73; 95% CI = 1.82-4.10) had a higher dementia risk than OH-free and robust people. Moreover, frail people, independently of the presence of OH, had higher mortality rate than OH-free and robust people. In individuals who developed dementia during the follow-up period, neither OH nor frailty was significantly associated with mortality.

Conclusions

Older adults with OH, whether robust or frail, may have a higher dementia risk than those without OH. Older adults with OH, when having frailty, may have a higher mortality rate than those without OH. The concurrent assessments of OH and frailty may provide prognostic values in terms of dementia and mortality risk in older adults.

Background and aims: Transportation noise is an environmental exposure with mounting evidence of adverse health effects. Besides the increased risk of cardiovascular and metabolic diseases, recent studies suggest that long-term noise exposure might accelerate cognitive decline in older age. We examined the association between transportation noise and cognitive function in a cohort of older adults.

Methods: The present study is based on 2594 dementia-free participants aged 60 + years from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K). Global cognition score and CIND (cognitive impairment, no dementia) were assessed with a comprehensive neuropsychological battery at baseline and up to 16 years. Residential transportation noise resulting from road traffic, railway, and aircraft were estimated at the most exposed façade and the time-weighted average exposure was assessed. Linear mixed-effect models were used to assess the effect of long-term traffic noise exposure on the rate of change in global cognition score. Hazard ratios (HRs) and 95 % confidence intervals (CIs) of CIND by transportation noise exposure were obtained with Cox proportional hazard models.

Results: Global cognition score decreased at an average rate of −0.041 (95 %CI −0.043, −0.039) per year. Aircraft noise was associated with a 0.007 (per 10 dB L_den; 95 %CI −0.012, −0.001) faster annual rate of decline. Global cognition score seems to be not affected by road traffic and railway noise. During the follow-up, 422 (21 %) participants developed CIND. A 10-dB L_den difference in exposure to aircraft and railway noise was associated with a 16 % (HR 1.16, 95 %CI 0.91, 1.49) and 26 % (HR 1.26, 95 %CI 1.01, 1.56) increased hazard of CIND in the multi-pollutant model, respectively. No association was found for road traffic (HR 1.00, 95 %CI 0.83, 1.21).

Conclusions: Transportation noise was linked to cognitive impairment and faster cognitive decline among older adults. Future studies are warranted to confirm our results.

Background: There is insufficient investigation of multiple imputation for systematically missing discrete variables in individual participant data meta-analysis (IPDMA) with a small number of included studies. Therefore, this study aims to evaluate the performance of three multiple imputation strategies - fully conditional specification (FCS), multivariate normal (MVN), conditional quantile imputation (CQI) - on systematically missing data on gait speed in the Swedish National Study on Aging and Care (SNAC).

Methods: In total, 1 000 IPDMA were simulated with four prospective cohort studies based on the characteristics of the SNAC. The three multiple imputation strategies were analysed with a two-stage common-effect multivariable logistic model targeting the effect of three levels of gait speed (100% missing in one study) on 5-years mortality with common odds ratios set to OR₁ = 0.55 (0.8-1.2 vs ≤0.8 m/s), and OR₂ = 0.29 (>1.2 vs ≤0.8 m/s).

Results: The average combined estimate for the mortality odds ratio OR₁ (relative bias %) were 0.58 (8.2%), 0.58 (7.5%), and 0.55 (0.7%) for the FCS, MVN, and CQI, respectively. The average combined estimate for the mortality odds ratio OR₂ (relative bias %) were 0.30 (2.5%), 0.33 (10.0%), and 0.29 (0.9%) for the FCS, MVN, and CQI respectively.

Conclusions: In our simulations of an IPDMA based on the SNAC where gait speed data was systematically missing in one study, all three imputation methods performed relatively well. The smallest bias was found for the CQI approach.

Introduction: We evaluated markers of olfactory dysfunction (OD) for estimating hazard of dementia in older adults.

Methods: Mild (hyposmia) and severe (anosmia) OD was classified in a population-based study of dementia-free persons (SNAC-K; n = 2473; mean age = 70 years) using the Sniffin sticks odor identification task. Combined variables were created for objective and subjective OD and for OD and APOE status. Hazard of dementia across 12 years was estimated with Cox regression.

Results: OD was associated with increased hazard of dementia (2.01; 95% confidence interval [CI] 1.60-2.52), with the strongest association for anosmia (2.92; 95% CI 2.14-3.98). Results remained consistent after adjusting for potential confounders and across age and sex subgroups. APOE ε4 carriers with anosmia had the highest hazard of dementia (ε4: 6.95; 95% CI 4.16-11.62; ε4/ε4: 19.84; 95% CI 6.17-63.78).

Discussion: OD is associated with increased risk of dementia, especially severe impairment in combination with genetic risk of Alzheimer's disease.

Background and aim: Accumulation of evidence has raised concern regarding the harmful effect of air pollution on cognitive function, but results are diverging. We aimed to investigate the longitudinal association of long-term exposure to air pollutants and cognitive impairment and its further progression to dementia in older adults residing in an urban area.

Methods: Data were obtained from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Cognitive impairment, no dementia (CIND) was assessed by a comprehensive neuropsychological battery (scoring >= 1.5 standard deviations below age-specific means in >= 1 cognitive domain). We assessed long-term residential exposure to particulate matters (PM2.5 and PM10) and nitrogen oxides (NOx) with dispersion modeling. The association with CIND was estimated using Cox proportional hazards models with 3-year moving average air pollution exposure. We further estimated the effect of long-term air pollution exposure on the progression of CIND to dementia using Cox proportional hazards models.

Results: Among 1987 cognitively intact participants, 301 individuals developed CIND during the 12-year followup. A 1-mu g/m(3) increment in PM2.5 exposure was associated with a 75% increased risk of incident CIND (HR = 1.75, 95 %CI: 1.54, 1.99). Weaker associations were found for PM10 (HR for 1-mu g/m(3) = 1.08, 95 %CI: 1.03-1.14) and NOx (HR for 10 mu g/m(3) = 1.18, 95 %CI: 1.04-1.33). Among those with CIND at baseline (n = 607), 118 participants developed dementia during follow-up. Results also show that exposure to air pollution was a risk factor for the conversion from CIND to dementia (PM2.5: HR for 1-mu g/m(3) = 1.90, 95 %CI: 1.48-2.43; PM10 : HR for 1-mu g/m(3) = 1.14, 95 %CI: 1.03-1.26; and NOR: HR for 10 mu g/m(3) = 1.34, 95 %CI: 1.07-1.69).

Conclusion: We found evidence of an association between long-term exposure to ambient air pollutants and incidence of CIND. Of special interest is that air pollution also was a risk factor for the progression from CIND to dementia.

Background: There is a growing interest in generating precise predictions of survival to improve the assessment of health and life-improving interventions. We aimed to (a) test if observable characteristics may provide a survival prediction independent of chronological age; (b) identify the most relevant predictors of survival; and (c) build a metric of multidimensional age.

Methods: Data from 3 095 individuals aged >= 60 from the Swedish National Study on Aging and Care in Kungsholmen. Eighty-three variables covering 5 domains (diseases, risk factors, sociodemographics, functional status, and blood tests) were tested in penalized Cox regressions to predict 18-year mortality.

Results: The best prediction of mortality at different follow-ups (area under the receiver operating characteristic curves [AUROCs] 0.878-0.909) was obtained when 15 variables from all 5 domains were tested simultaneously in a penalized Cox regression. Significant prediction improvements were observed when chronological age was included as a covariate for 15- but not for 5- and 10-year survival. When comparing individual domains, we find that a combination of functional characteristics (ie, gait speed, cognition) gave the most accurate prediction, with estimates similar to chronological age for 5- (AUROC 0.836) and 10-year (AUROC 0.830) survival. Finally, we built a multidimensional measure of age by regressing the predicted mortality risk on chronological age, which displayed a stronger correlation with time to death (R = -0.760) than chronological age (R = -0.660) and predicted mortality better than widely used geriatric indices.

Conclusions: Combining easily accessible characteristics can help in building highly accurate survival models and multidimensional age metrics with potentially broad geriatric and biomedical applications.

Background: To identify brain magnetic resonance imaging (MRI) signatures characterizing people with different patterns of decline in cognition and motor function.

Methods: In the Swedish National Study on Aging and Care in Kungsholmen, Stockholm, 385 participants had available repeated brain MRI examinations, where markers of brain volumes and white matter integrity were assessed. The speed of cognitive and motor decline was estimated as the rate of a Mini-Mental State Examination and gait speed decline over 12 years (linear mixed models), and further dichotomized into the upper (25% fastest rate of decline) versus the lower quartiles. Participants were grouped in slow/no decliners (reference), isolated motor decliners, isolated cognitive decliners, and cognitive and motor decliners. We estimated the associations between changes in brain markers (linear mixed models) and baseline diffusion tensor imaging measures (linear regression model) and the 4 decline patterns.

Results: Individuals with concurrent cognitive and motor decline (n = 51) experienced the greatest loss in the total brain (β: −12.3; 95% confidence interval [CI]: −18.2; −6.38) and hippocampal (β: −0.25; 95% CI: −0.34; −0.16) volumes, the steepest accumulation of white matter hyperintensities (β: 1.61; 95% CI: 0.54; 2.68), and the greatest ventricular enlargement (β: 2.07; 95% CI: 0.67; 3.47). Compared to the reference, those only experiencing cognitive decline presented with steeper hippocampal volume loss, whereas those exhibiting only motor decline displayed a greater white matter hyperintensities burden. Lower microstructural white matter integrity was associated with concurrent cognitive and motor decline.

Conclusion: Concurrent cognitive and motor decline is accompanied by rapidly evolving and complex brain pathology involving both gray and white matter. Isolated cognitive and motor declines seem to exhibit brain damage with different qualitative features.

BACKGROUND: Olfactory impairment is increasingly common with older age, which may be in part explained by cumulative effects of exposure to inhaled toxins. However, population-based studies investigating the relationship between air pollution and olfactory ability are scarce.

OBJECTIVES: We aimed to investigate associations between exposure to common air pollutants and longitudinal change in odor identification.

METHODS: Our study of 2,468 participants (mean age = 72.3 y; 61.1% female), of which 1,774 participants (mean age = 70.5 y; 61.9% female) had at least two olfactory assessments over 12 y of follow-up from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), Stockholm, Sweden. Participants were free from cognitive impairment and neurodegenerative disease at baseline. Odor identification ability was assessed with Sniffin' Sticks. Change in olfactory performance was estimated with linear mixed models. Exposure to two major airborne pollutants [particulate matter with aerodynamic diameter <= 2.5 mu m (PM2.5) and nitrogen oxides (NOx)] for the 5 y preceding baseline was assessed using spatiotemporal dispersion models for outdoor levels at residential addresses.

RESULTS: Participants showed significant decline in odor identification ability for each year in the study {f3 = - 0.20 [95% confidence interval (CI): -0.22, 0.18; p < 0.001]}. After adjustment for all covariates, residents of third [f3= - 0.09 (95% CI: -0.14, -0.04; p < 0.001)] and fourth [f3 = - 0.07 (95% CI: -0.12, -0.02; p = 0.005)] exposure quartiles of PM2.5 had faster rates of olfactory decline than residents from the first quartile. Similar results were observed for the third [f3= - 0.05 (95% CI: -0.10, -0.01; p = 0.029)] and fourth [f3= - 0.07 (95% CI: -0.11, -0.02; p = 0.006) quartiles of NOx].

DISCUSSION: Our results suggest an association between air pollution exposure and subsequent olfactory decline. We speculate that cumulative effects of airborne pollutants on the olfactory system may be one underlying cause of olfactory impairment in aging. 

Background: Diabetes has been related to disability and excess mortality. We estimated the extent to which diabetes shortens disability-free survival and identified modifiable factors that may prolong disability-free survival in older adults with diabetes.

Methods: Disability-free older adults (n = 2 216, mean age: 71 years, female: 61%) were followed for up to 15 years. Diabetes was ascertained through medical examinations, medication use, or glycated hemoglobin ≥6.5% (48 mmol/mol). Disability-free survival was defined as survival until the occurrence of disability. A favorable (vs unfavorable) lifestyle profile was defined as the presence of at least 1 of the following: healthy (vs unhealthy) behaviors, active (vs inactive) engagement in leisure activities, or moderate-to-rich (vs poor) social network. Data were analyzed using Cox regression and Laplace regression.

Results: During the follow-up, 1 345 (60.7%) participants developed disability or died. Diabetes, but not prediabetes, was related to the outcome (hazard ratio [HR] 1.29, 95% CI 1.06–1.57), and 2.15 (1.02–3.27) years shorter median disability-free survival. In joint exposure analysis, disability-free survival was shortened by 3.29 (1.21–5.36), 3.92 (2.08–5.76), and 1.66 (0.06–3.28) years for participants with diabetes plus unhealthy behaviors, inactive engagement in leisure activities, or poor social network. Among participants with diabetes, a favorable profile led to a nonsignificant HR of 1.19 (0.93–1.56) for disability/death and prolonged disability-free survival by 3.26 (2.33–4.18) years compared to those with an unfavorable profile.

Conclusions: A healthy and socially active lifestyle may attenuate the risk of diabetes on disability or death and prolong disability-free survival among people with diabetes.

Background: Acute clinical events, such as pneumonia, may impact physical functionality but their effect on cognition and the possible duration of this effect remains to be quantified. This study investigated the impact of pneumonia on cognitive trajectories and dementia development in older people.

Methods: Data were obtained from 60+ years old individuals, who were assessed from 2001 to 2018 in the population-based SNAC-K study (Sweden). Participants were eligible if they were not institutionalized, had no dementia, and did not experience pneumonia 5 years prior to baseline (N = 2 063). A propensity score was derived to match 1:3 participants hospitalized with a diagnosis of pneumonia (N = 178), to nonexposed participants (N = 534). Mixed linear models were used to model cognitive decline. The hazard of dementia, clinically diagnosed by physicians following Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV, was estimated using Cox regression models.

Results: We found a transient impact of pneumonia on cognitive decline in the first 2.5 years (B = −0.94, 95% confidence interval [CI] −1.75, −0.15). The hazard ratio (HR) for dementia was not statistically significantly increased in pneumonia participants (HR = 1.17, 95%CI 0.82, 1.66).

Conclusions: The transient impact of pneumonia on cognitive function suggests an increased need of health care for patients after a pneumonia-related hospitalization and reinforces the relevance of pneumonia prevention.