Introduction: Cognitive reserve (CR) describes individual differences in susceptibility to brain damage that translates into varying dementia onsets and may also influence the occurrence of depressive symptoms. Within a population-based cohort of older people, we investigated two operationalizations of CR, residual- and activity-based approaches, in their association with the development of depressive symptoms.

Methods: We analyzed longitudinal data on 402 dementia- and depression-free adults aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) who underwent brain MRI at baseline. Residual-based reserve was derived by regressing episodic memory on a brain-integrity index incorporating six structural MRI markers. Activity-based reserve factored lifelong CR-enhancing experiences, including education, work complexity, social network, and leisure activities. Clinically relevant depressive symptoms were defined as a Montgomery–Åsberg Depression Rating Scale score >6. Cox hazard models were used to explore the association between both residual- and activity-based CR measures (categorized in tertiles) and incidence of depressive symptoms over a 15-year follow-up, while accounting for sociodemographic, clinical, behavioral factors, and brain integrity. Analyses for the activity-based measure were replicated in the full SNAC-K sample (N = 2709), further exploring depression diagnosis as additional outcome.

Results: Compared to low levels, higher levels of residual-based CR were associated with a lower hazard of depressive symptom onset in fully adjusted models (HR: .43, 95%CI .22, .84). While activity-based CR was not significantly associated with developing depressive symptoms in the MRI subsample (HRhigh .47, 95%CI .21, 1.04), it was in the full sample (HRhigh .52, 95%CI .39, .71). Activity-based CR was further associated with depression diagnoses in the full sample (HRhigh: .45, 95%CI .31, .65).

Discussion: Largely independent of its measurement, CR appears to influence depressive symptomatology in late life. Reserve-enhancing initiatives may be beneficial not only for cognitive but also for mental health in older people.

INTRODUCTION: We investigated the association of cognitive reserve (CR) with transitions across cognitive states and death. METHODS: This population-based cohort study included 2631 participants (age ≥60 years) who were dementia-free at baseline and regularly examined up to 15 years. Data were analyzed using the Markov multistate models. RESULTS: Each 1-point increase in the composite CR score (range: -4.25 to 3.46) was significantly associated with lower risks of transition from normal cognition to cognitive impairment, no dementia (CIND) (multivariable-adjusted hazards ratio = 0.78; 95% confidence interval = 0.72–0.85) and death (0.85; 0.79–0.93), and from CIND to death (0.82; 0.73–0.91), but not from CIND to normal cognition or dementia. A greater composite CR score was associated with a lower risk of transition from CIND to death in people aged 60-72 but not in those aged ≥ 78 years. DISCUSSION: CR contributes to cognitive health by delaying cognitive deterioration in the prodromal phase of dementia. Highlights: We use Markov multistate model to examine the association between cognitive reserve and transitions across cognitive states and death. A great cognitive reserve contributes to cognitive health by delaying cognitive deterioration in the prodromal phase of dementia. A great cognitive reserve is associated with a lower risk of transition from cognitive impairment, no dementia to death in people at the early stage of old age, but not in those at the late stage of old age.

INTRODUCTION: We quantified the association of mild (ie, involving one or two body systems) and complex (ie, involving ≥3 systems) multimorbidity with structural brain changes in older adults.

METHODS: We included 390 dementia-free participants aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen who underwent brain magnetic resonance imaging at baseline and after 3 and/or 6 years. Using linear mixed models, we estimated the association between multimorbidity and changes in total brain tissue, ventricular, hippocampal, and white matter hyperintensities volumes.

RESULTS: Compared to non-multimorbid participants, those with complex multimorbidity showed the steepest reduction in total brain (β*time −0.03, 95% CI −0.05, −0.01) and hippocampal (β*time −0.05, 95% CI −0.08, −0.03) volumes, the greatest ventricular enlargement (β*time 0.03, 95% CI 0.01, 0.05), and the fastest white matter hyperintensities accumulation (β*time 0.04, 95% CI 0.01, 0.07).

DISCUSSION: Multimorbidity, particularly when involving multiple body systems, is associated with accelerated structural brain changes, involving both neurodegeneration and vascular pathology.

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.

INTRODUCTION: The presence of multiple cardiometabolic diseases (CMDs) has been linked to increased dementia risk, but the combined influence of CMDs on cognition and brain structure across the life course is unclear.

METHODS: In the UK Biobank, 46,562 dementia-free participants completed a cognitive test battery at baseline and a follow-up visit 9 years later, at which point 39,306 also underwent brain magnetic resonance imaging. CMDs (diabetes, heart disease, and stroke) were ascertained from medical records. Data were analyzed using age-stratified (middle age [< 60] versus older [≥ 60]) mixed-effects models and linear regression.

RESULTS: A higher number of CMDs was associated with significantly steeper global cognitive decline in older (β = –0.008; 95% confidence interval: −0.012, −0.005) but not middle age. Additionally, the presence of multiple CMDs was related to smaller total brain volume, gray matter volume, white matter volume, and hippocampal volume and larger white matter hyperintensity volume, even in middle age.

DISCUSSION: CMDs are associated with cognitive decline in older age and poorer brain structural health beginning already in middle age.

Objective: We investigated whether vascular risk factors (VRFs), assessed with Life’s Simple 7 (LS7), are associated with the rate of cognitive decline in the years preceding a dementia diagnosis. Method: This study included 1,449 stroke-free participants aged ≥60 years from the Swedish National Study on Aging and Care in Kungsholmen, who underwent repeated neuropsychological testing (episodic memory, semantic memory, verbal fluency, perceptual speed) across 12 years. The LS7 score, assessed at baseline, included smoking, diet, physical activity, body mass index, plasma glucose, total cholesterol, and blood pressure. Preclinical dementia was defined as being dementia-free at baseline and diagnosed with dementia during follow-up. Level and change in cognitive performance as a function of LS7 category (poor vs. intermediate to optimal) and future dementia status were estimated using linear mixed-effect models. Results: Participants who later developed dementia had, on average, a poorer LS7 score compared to those who remained dementia-free. For individuals aged 60–72 years, poor diet was associated with accelerated decline in perceptual speed (β = −0.05, 95% CI [−0.08, −0.02]), and a poor glucose score was associated with faster rates of verbal fluency (β = −0.019, 95% CI [−0.09, −0.01]) and global cognitive (β = −0.028, 95% CI [−0.06, 0.00]) decline in the preclinical dementia group. Conclusions: VRFs exacerbate rate of cognitive decline in the years preceding a dementia diagnosis. This effect was most pronounced in young–old age and primarily driven by diet and glucose. The effect of VRFs may be especially detrimental for cognitive decline trajectories of individuals with impending dementia.

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: We sought to examine the associations of the Lifestyle for Brain Health (LIBRA) index with cognitive function among rural Chinese older adults and to explore the potential role of cluster of differentiation 33 gene (CD33) in the associations. Methods: This population-based cross-sectional study included 4914 dementia-free participants (age ≥60 years; 56.43 % women) in the 2018 baseline examination of MIND-China. The LIBRA index was generated from 11 factors. We used a neuropsychological test battery to assess episodic memory, verbal fluency, attention, executive function, and global cognition. The CD33(rs3865444) polymorphism was detected using multiple-polymerase chain reaction amplification. Data were analyzed using the general linear regression models. Results: A higher LIBRA index was associated with multivariable-adjusted β-coefficient (95 %CI) of -0.011(-0.020- -0.001) for global cognitive z-score, -0.020(-0.033- -0.006) for episodic memory, and -0.016(-0.029- -0.004) for verbal fluency. The CD33(rs3865444) was associated with a lower global cognitive z-score in the additive (CA vs. CC: β-coefficient=0.042; 95 %CI=0.008–0.077), the dominant (CA+AA vs. CC: 0.040; 0.007–0.073), and the over-dominant (CA vs. CC+AA: 0.043; 0.009–0.077) models. Similar results were obtained for verbal fluency and attention. The CD33 gene showed statistical interactions with LIBRA index on cognitive function (Pinteraction<0.05) such that a higher LIBRA index was significantly associated with lower z-scores of global cognition and attention only among CD33 CC carriers (P < 0.05). Conclusions: This population-based study reveals for the first time that a higher LIBRA index is associated with worse cognitive performance in rural Chinese older adults and that CD33 gene could modify the association.

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.

Objective: Individual aspects of social health (SH; eg, network, engagement, support) have been linked to cognitive health. However, their combined effect and the role of the structural properties of the brain (brain reserve [BR]) remain unclear. We investigated the interplay of SH and BR on cognitive change in older adults.

Methods: Within the Swedish National Study on Aging and Care–Kungsholmen, 368 dementia-free adults aged ≥60 years with baseline brain magnetic resonance imaging were followed over 12 years to assess cognitive change. A measure of global cognition was computed at each of the 5 waves of assessment by averaging domain-specific Z scores for episodic memory, perceptual speed, semantic memory, and letter and category fluency. An SH composite score was computed at baseline by combining leisure activities and social network. BR was proxied by total brain tissue volume (TBTV). Linear mixed models (adjusted for sociodemographic, vascular, and genetic factors) were used to estimate cognitive trajectories in relation to SH and TBTV. Interaction analysis and stratification were used to examine the interplay between SH and TBTV.

Results: Moderate–good SH (n = 245; vs poor, β-slope = 0.01, 95% confidence interval [CI] = 0.002–0.02, p = 0.018) and moderate-to-large TBTV (n = 245; vs small, β-slope = 0.03, 95% CI = 0.02–0.04, p < 0.001) were separately associated with slower cognitive decline. In stratified analysis, moderate–good SH was associated with higher cognitive levels (but not change) only in participants with moderate-to-large TBTV (β-intercept = 0.21, 95% CI = 0.06–0.37, p < 0.01; interaction SH * TBTV, p < 0.05).

Interpretation: Our findings highlight the interplay between SH and BR that likely unfolds throughout the entire life course to shape old-age cognitive outcomes.