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Background: Lung function has been associated with cognitive decline and dementia, but the extent to which lung function impacts brain structural changes remains unclear. We aimed to investigate the association of lung function with structural macro‐ and micro‐ brain changes across mid‐ and late‐ life in a large population‐based cohort study. Method: The study included a total of 37,590 neurologic disorder‐free participants aged 40‐70 years from the UK Biobank, who underwent brain magnetic resonance imaging (MRI) scans 9 years after baseline. After 2.5 years, a subsample (n = 3,941) underwent a second MRI scan. Lung function was assessed using a composite score based on forced expiratory volume in 1 second, forced vital capacity, and peak expiratory flow, and divided into tertiles (i.e., low, moderate, and high). Regional brain volumes (including total brain, gray matter, white matter, hippocampus, and white matter hyperintensities) and diffusion markers (fractional anisotropy [FA] and mean diffusivity [MD]) were assessed. Data were analyzed using linear regression and mixed‐effects models. Result: At baseline, lung function ranged from ‐3.43 to 22.91 among all participants. In multi‐adjusted linear regression, low lung function was dose‐dependently related to smaller brain volumes and lower white matter integrity. Compared to high lung function, low lung function was associated with smaller total brain (β [95% CI]: ‐0.083 [‐0.097, ‐0.070], gray matter ‐0.145 [‐0.161, ‐0.130], white matter ‐0.017 [‐0.031, ‐0.004], and hippocampal ‐0.102 [‐0.128, ‐0.075]) volume, as well as poor white matter health (FA ‐0.165 [‐0.195, ‐0.135] for lower, WMH 0.269 [0.242, 0.295] and MD 0.168 [0.140, 0.196] for higher). Over the 2.5 years follow‐up, low PF was associated with reduced white matter (‐0.021 [‐0.041, ‐0.002]) and hippocampal (‐0.078 [‐0.110, ‐0.046]) volume, reduced FA (‐0.063 [‐0.091, ‐0.035]), and increased WMH volume (0.065 [0.016, 0.114]) and MD (0.121 [0.089, 0.154]). After stratification by age, the associations remained significant among adults aged 40‐60 years and 60+ years. Conclusion: Low lung function is associated with macro‐ and micro‐ structural brain changes involving both neurodegenerative and vascular pathologies. This association is significant in both mid‐ and late‐ life. [ABSTRACT FROM AUTHOR]

Introduction: The relationship between impaired kidney function (KF), dementia, and brain pathologies remains unclear. Methods: A total of 1354 dementia‐ and kidney disease‐free participants including 895 with normal and 459 with impaired KF were followed from 2002 until 2020 (median [interquartile range]: 5 [2–9]) to detect incident dementia. KF was assessed at baseline and categorized as normal or impaired. Over the follow‐up, 453 participants died and underwent autopsies for neuropathological assessment. Results: Compared to those with normal KF, the hazard ratios (95% confidence intervals [CIs]) of those with impaired KF was 1.48 (1.15, 1.90)/1.44 (1.10, 1.88) for dementia/Alzheimer's dementia. Furthermore, impaired KF was related to a significantly higher burden of cerebral amyloid angiopathy (CAA; odds ratio = 1.96, 95% CI: 1.17, 3.30), but not to other brain pathologies. Discussion: Impaired KF is associated with an increased risk of dementia and Alzheimer's dementia. CAA may underlie, in part, this association. Highlights: Impaired kidney function (KF) was associated with higher dementia and Alzheimer's dementia risk.Impaired KF anticipated dementia and Alzheimer's dementia onset by more than 1.5 years.Impaired KF was significantly related to a higher burden of cerebral amyloid angiopathy (CAA) but not to other brain pathologies. [ABSTRACT FROM AUTHOR]

Introduction: The association between cognitive reserve (CR) and survival with independence is unknown. We examined whether lifelong CR accumulation is associated with disability‐free survival and explored the extent to which cognitive function mediates this association. Methods: Within the Rush Memory and Aging Project, 1633 dementia‐ and disability‐free participants were followed annually for up to 22 years. Lifelong CR including education, early‐/mid‐/late‐life cognitive activities, and late‐life social activity was assessed and tertiled. Results: CR score was dose‐dependently associated with disability/death (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.93–0.99). Compared to low CR, the HR (95% CI) of disability/death was 0.82 (0.70–0.95) for high CR. The median disability‐free survival time was prolonged by 0.99 (95% CI 0.28–1.71) years for participants with high CR. Cognitive function mediated 35.7% of the association between CR and disability‐free survival. Discussion: High lifelong CR was associated with prolonged disability‐free survival. Cognitive function mediates about one‐third of this association. Our findings underscore the importance of CR for healthy aging. [ABSTRACT FROM AUTHOR]

Introduction: The relationship between pulmonary function (PF) and mild cognitive impairment (MCI), dementia, and brain pathologies remains unclear. Methods: A total of 1312 dementia‐free participants, including a cognitively intact group (n = 985) and an MCI group (n = 327), were followed for up to 21 years to detect incident MCI and dementia. PF was assessed at baseline with a composite score and tertiled. Over follow‐up, 540 participants underwent autopsies for neuropathological assessment. Results: Compared to the highest PF, the hazard ratios (95% confidence intervals [CIs]) of the lowest PF were 1.95 (1.43‐2.66) for MCI in the cognitively intact group and 1.55 (1.03‐2.33) for dementia in the MCI group. Low PF was further related to Alzheimer's disease pathology (odds ratio [OR] 1.32, 95% CI 1.19‐1.47) and vascular pathology (OR 3.05, 95% CI 1.49‐6.25). Discussion: Low PF increases MCI risk and accelerates MCI progression to dementia. Both neurodegenerative and vascular mechanisms may underlie the PF‐dementia association. [ABSTRACT FROM AUTHOR]

Background: The association of pulmonary function (PF) with mild cognitive impairment (MCI) and its underlying mechanisms remain unclear. We examined the association of PF with MCI and its progression to dementia, and brain pathologies. Method: Within the Rush Memory and Aging Project, the 1,312 dementia‐free participants (mean age: 79.41±7.77 years) included a cognitively intact group (n = 985) and an MCI group (n = 327). The two groups were followed for up to 21 years to detect incident MCI and dementia. PF was assessed with a composite score based on forced vital capacity, forced expiratory volume in 1s, and peak expiratory flow measured at baseline, and further divided into tertiles (i.e., lowest, middle, and highest). MCI and dementia were diagnosed following standard criteria. During the follow‐up, 540 participants died and underwent autopsies for neuropathological assessment (including Alzheimer's disease [AD], and vascular brain pathologies). Data were analyzed using Cox regression, Laplace regression, and logistic regression. Result: During the follow‐up (median 7 years, interquartile range 4‐10 years), 461 participants developed MCI in the cognitively intact group, and 324 had dementia among participants with MCI. Compared to the highest PF, the multi‐adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were 1.95 (1.43‐2.66) for MCI in the cognitively intact group, and 1.55 (1.03‐2.33) for dementia in the MCI group, respectively. The median time from MCI to dementia development was 2.75 (95% CI: 2.15‐3.34) years shorter in people with the lowest PF than those with the highest PF. In the pathological data analysis, the lowest PF was significantly related to higher AD pathology (odds ratio [OR]: 1.32, 95% CI 1.19‐1.47) and vascular brain pathologies (OR: 3.05, 95% CI 1.49‐6.25) compared to the highest PF. Conclusion: The lowest PF is associated with nearly 2‐fold risk of MCI and accelerates progression from MCI to dementia by almost 3 years. Both neurodegenerative and vascular mechanisms may underlie this association. [ABSTRACT FROM AUTHOR]

The association of poor pulmonary function (PF) with cognitive trajectories and structural brain differences remains unclear. Within the Rush Memory and Aging Project, 1377 dementia‐free subjects were followed up to 21 years. PF was assessed with a composite score measured at baseline. Global and domain‐specific cognitive function was assessed annually constructed from 19 cognitive tests. A subsample of 351 participants underwent brain magnetic resonance imaging to investigate the cross‐sectional association between PF and structural brain volumes. We found that low PF was related to faster decline in global cognition, and domain‐specific function including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed. In addition, low PF was associated with smaller volumes of total brain, white matter and gray matter, and larger white matter hyperintensities volume. Our results suggest that low PF is associated with faster cognitive decline, and both neurodegeneration and vascular brain lesions may underlie the association. [ABSTRACT FROM AUTHOR]

Background: Cognitive reserve (CR) contributes to preserving cognition when facing brain aging and damage. CR has been linked to reduced dementia risk in late life. However, the association between CR and brain imaging measures, especially in mid‐life, is unclear. We aimed to explore the association of CR with cognitive decline and structural brain differences in mid‐ and late life. Method: Within the UK Biobank, 42,301 dementia‐free participants aged 40‐70 were followed for a median of 9 (interquartile range: 8 to 10) years. Latent class analysis was used to generate an indicator of CR (categorized as high, moderate, and low) based on education, occupation, and multiple cognitively stimulating activities at baseline. Cognitive tests for global and domain‐specific cognitive function were administrated at baseline and follow‐up. A subsample (n = 34,041) underwent brain magnetic resonance imaging (MRI) scans at the follow‐up examination. Volumes of total brain, white matter, grey matter, hippocampus, and white matter hyperintensities (TBV, WMV, GMV, HV, and WMHV) were assessed. Data were analyzed using mixed‐effects models and linear regression. Result: At baseline, 16,032 (37.90%), 10,709 (25.32%), and 15,560 (36.78%) participants had low, moderate, and high levels of CR, respectively. In multi‐adjusted mixed‐effects models, compared to low CR, high CR was associated with a slower decline in global cognitive function (β [95% confidence interval, CI]: 0.10 [0.08, 0.11]), prospective memory (0.10 [0.06, 0.15]), fluid intelligence (0.07 [0.04, 0.10]), and reaction time (0.04 [0.02, 0.06]). In MRI data analysis, high CR was related to lesser TBV (‐0.03 [‐0.04, ‐0.02]), WMV (‐0.03 [‐0.04, ‐0.02], GMV (‐0.02 [‐0.04, ‐0.01]), and WMHV (‐0.03 [‐0.05, ‐0.002]), but greater HV (0.04 [0.02, 0.06]) compared to low CR. In analyses stratified by baseline age, the significant associations between high CR and global cognition and TBV were present among both mid‐life (<60 years) and late‐life (≥60 years) participants. The CR‐cognitive decline association remained significant after additional adjustment for MRI measures. Conclusion: Higher CR is associated with slower cognitive decline, lesser TBV, greater HV, and lower microvascular burden, especially in mid‐life. The protective role of high CR on cognition is independent of structural brain differences. [ABSTRACT FROM AUTHOR]

Background: The association between kidney function (KF) and dementia risk and the mechanisms underlying this relationship remain unclear. We aimed to examine the association of impaired KF with dementia and structural brain differences on magnetic resonance imaging (MRI). Method: Within the UK biobank, 191,970 dementia‐free participants aged ≥60 (mean age: 64.1 ± 2.9 years) were followed for 16 years to detect incident dementia. Serum creatinine and cystatin C were measured at baseline to calculate estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) using the Chronic Kidney Disease Epidemiology Collaboration equation. KF was categorized as normal (eGFR ≥ 90), mildly impaired (60 £ eGFR < 90), or moderately to severely impaired (eGFR < 60). Dementia was assessed based on self‐reported medical history and medical records. During the follow‐up, a subsample of 12,637 participants underwent brain MRI scans. Volumes of total brain, gray matter, white matter, hippocampus, and white matter hyperintensities were assessed. Data were analyzed using Cox regression, Laplace regression, and linear regression. Result: Of all participants, 122,463 (63.8%) had mildly impaired KF and 8,670 (4.5%) had moderate to severely impaired KF at baseline. Over the follow‐up (median [interquartile range]: 12.8 [11.9‐13.5] years), 5,327 (2.8%) participants developed dementia. In multi‐adjusted Cox regression, eGFR was dose‐dependently associated with dementia (per 1‐standard‐deviation decrease in eGFR; hazard ratio [HR] 95% confidence interval [CI]: 1.10 [1.07‐1.14]). Compared to normal KF, there was an increased risk of dementia with moderate to severely impaired KF (HR 1.53, 95% CI 1.32‐1.76) but not mildly impaired KF. In Laplace regression, dementia onset among people with moderate to severely impaired KF occurred 1.53 (95% CI: 0.98–2.08) years earlier than those with normal KF. Moderate to severely impaired KF was related to significantly lower gray matter volume (β = ‐0.11, 95% CI: ‐0.19– ‐0.03), but not to other brain MRI measures. Conclusion: Impaired KF is associated with about 50% increased risk of dementia and anticipates dementia onset by more than 1.5 years. Brain neurodegeneration may underlie the KF‐dementia association. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular health (CVH) has been associated with cognitive decline and dementia, but the extent to which CVH impact brain age remains unclear. We aimed to investigate the association of CVH assessed by Life's Essential 8 (LE8) score with neuroimaging‐based brain age and brain predicted age difference (PAD). Method: The study included a total of 34098 participants (mean age 54.82±7.50 years; 53.21% female) from the UK Biobank, who underwent brain magnetic resonance imaging (MRI) scans 9 years after baseline. A brain age prediction model with the best prediction performance was trained from 9 candidate models (Lasso, support vector regression, and XGBoost, with or without the addition of 2 variable selection methods, respectively) based on T1‐weighted MRI, T2‐FLAIR, T2∗, diffusion‐MRI, task fMRI, and resting‐state fMRI in 4355 healthy participants. Using the model, we calculated brain age and brain PAD (predicted age‐chronological age). Baseline LE8 score was calculated by the mean score of 8 metrics (diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure) and tertiled as low, moderate, and high CVH. Data were analyzed using linear regression models. Result: At baseline, LE8 score was ranged from 15.00 to 100.00. In linear regression adjusted for age, sex and education, better CVH was associated with younger brain age (β [95% CI]: ‐0.029 [‐0.032, ‐0.026]) and smaller brain PAD (β [95% CI]: ‐0.033 [‐0.035, ‐0.030]). Compared to moderate CVH, low CVH was associated with older brain age (β [95% CI]: 0.444 [0.345, 0.543]) and bigger brain PAD (β [95% CI]: 0.513 [0.422, 0.604]), whereas high CVH was associated with younger brain age (β [95% CI]: ‐0.360 [‐0.459, ‐0.261]) and smaller brain PAD (β [95% CI]: ‐0.398 [‐0.489, ‐0.307]). The additional adjustment did not alter the relationships observed. After stratification by age, cardiovascular disease (CVD), or APOE ε4, the association remained significant among adults aged 40‐60 years and 60+ years, among CVD and non‐CVD, as well as among APOE ε4 carriers and non‐ carriers. Conclusion: Better cardiovascular health is associated with younger brain age and reduced brain PAD. This association is significant even in middle‐aged, non‐CVD and non‐carriers adults. [ABSTRACT FROM AUTHOR]

Background: The impact of cardiometabolic diseases (CMDs; including type 2 diabetes [T2D], heart disease [HD], and stroke) on cognitive trajectories and brain structural changes across the life course is unclear. We aimed to explore the association of patterns of co‐morbid CMDs with cognitive decline and structural brain MRI measures in mid‐ vs. late‐ life. Method: Within the UK Biobank, 46,562 dementia‐free participants aged 40‐70 were followed for 9 years. Baseline CMDs were ascertained medical records. A battery of 5 cognitive tests was administered at baseline and follow‐up and used to derive global and domain‐specific cognitive function scores. A subsample (n = 39,353) underwent brain magnetic resonance imaging (MRI) scans at the follow‐up examination. Volumes of total brain, white matter, grey matter, hippocampus, and white matter hyperintensities (TBV, WMV, GMV, HV, and WMHV) were assessed. Data were analyzed using multivariate adjusted mixed‐effects models and linear regression. Result: At baseline, 3,437 (7.4%) participants had 1 CMD and 297 (0.6%) had ≥2. In mixed‐effects models, the presence of any CMD was related to a steeper decline in global cognitive function (β [95% confidence interval]: ‐0.005 [‐0.008, ‐0.003]) as well as working memory (‐0.024 [‐0.033, ‐0.014]), visual declarative memory (‐0.004 [‐0.007, ‐0.001]), and processing speed (‐0.002 [‐0.002, ‐0.001]), especially for those with CMD profiles involving T2D and/or HD. In stratified analysis by age (mid‐ [<60] vs. late‐ [≥60] life), CMDs were related to a decline in only processing speed in mid‐life, while in late‐life, CMDs were additionally related to a decline in verbal/numeric reasoning. In linear regression, people with CMDs had significantly lower TBV (‐0.15 [‐0.18, ‐0.12]), GMV (‐0.17 [‐0.20, ‐0.14]), WMV (‐0.11 [‐0.14, ‐0.08]), HV (‐0.14 [‐0.18, ‐0.11]) and significantly higher WMH (0.05 [0.02, 0.09]), and this was exacerbated among people with ≥2 CMDs compared to 1 CMD. Similar results were observed in both mid‐ and late‐life. Conclusion: The presence of CMDs is associated global/domain‐specific cognitive decline and brain MRI measures involving neurodegenerative and vascular markers in both mid‐ and late‐ life. Our findings highlight the need for the effective management of CMDs in mid‐life for the prevention of dementing disorders in late‐life. [ABSTRACT FROM AUTHOR]

Background: The relationship of resting heart rate (RHR), a common indicator of cardiovascular health, with cognitive decline is unclear. We aimed to investigate the association of RHR with cognitive trajectory and brain age assessed by brain Magnetic Resonance Imaging (MRI) in the UK Biobank. Method: Within the UK Biobank 18,210 chronic brain disorders‐free participants aged 60+ were followed for up to 16 years. RHR was assessed by blood pressure monitor and categorized into <60, 60‐69 (reference), 70‐79, and ≥80 beats per minute (bpm). Cognitive function including global cognition, numeric memory, prospective memory, pairs matching, fluid intelligence, and reaction time was collected at baseline and each follow‐up wave. A subsample of 10,458 participants underwent brain MRI (T1‐weighted MRI, T2‐FLAIR, T2∗, diffusion‐MRI, task fMRI, and resting‐state fMRI) to detect brain age and brain predicted age difference (PAD) using Lasso regression. Data were analyzed using mixed‐effects model and linear regression model. Result: Compared to reference group, RHR≥80 bpm was associated with faster decline in global cognition (β: ‐0.03, 95% confidence interval [CI]: ‐0.05, ‐0.01) and reaction time (β: ‐0.03, 95% CI: ‐0.07, ‐0.01). In the MRI data analysis, RHR≥80 bpm was associated with older brain age (β [95% CI]: 0.50 [0.25, 0.76]) and bigger brain PAD (β [95% CI]: 0.50 [0.26, 0.74]). Conclusion: Higher RHR is associated with faster cognitive decline and older brain age. Monitoring and controlling elevated RHR could be a promising interventional target in preserving cognitive function. [ABSTRACT FROM AUTHOR]

Background: Kidney function has been linked to cognitive function, but its relation to dementia and mechanisms underlying this relation remains unclear. We aimed to examine the association of impaired kidney function with dementia and brain pathologies. Method: Within Rush Memory and Aging Project, 1380 dementia‐free subjects (75.22% female; mean age: 79.42±7.61 years) at baseline were followed for up to 22 years. Blood samples were taken at baseline and serum creatinine was measured to calculate estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula. Kidney function dichotomized as normal (eGFR ≥ 60 mL/min/1.73 m2) or impaired (eGFR <60 mL/min/1.73 m2). Dementia, including Alzheimer's dementia, was diagnosed following international criteria. During the follow‐up, 469 participants died and underwent autopsies for neuropathological assessment (including Alzheimer's disease [AD], vascular, and other brain pathologies). Data were analyzed using Cox regression, Laplace regression, and logistic regression. Result: At baseline, 895 (64.86%) participants with normal kidney function and 485 (35.14%) with impaired. Over follow‐up (median [interquartile range]: 5 [2–9] years), 300 (21.74%) participants developed dementia, including 273 (19.78%) with Alzheimer's dementia. In multi‐adjusted Cox regression, lower eGFR was does‐dependently associated with higher dementia risk (hazard ratio [HR] = 1.01, 95% confidence interval [CI]: 1.01–1.02, P = 0.003) and Alzheimer's dementia risk (HR = 1.01, 95% CI: 1.00‐1.02, P = 0.002). Compared to normal kidney function, impaired kidney function was associated with a greater risk of dementia (HR = 1.49, 95% CI: 1.16–1.91) and Alzheimer's dementia (HR = 1.45, 95% CI: 1.12–1.89). The median time to the development of dementia or Alzheimer's dementia was 2.48 (95% CI: 0.36–3.03) or 2.56 (95% CI: 0.37–2.79) years shorter in people with impaired vs. normal kidney function, respectively. In brain pathology analysis, impaired kidney function was significantly related to higher burdens of cerebral amyloid angiopathy (odds ratio = 2.03, 95% CI: 1.23–3.35). Conclusion: Impaired kidney function is associated with an increased risk of dementia and Alzheimer's dementia. Vascular mechanisms may underlie this association. [ABSTRACT FROM AUTHOR]

Background: Sleep duration has been linked to dementia risk; however, its association with cognitive functioning in specific domains and the underlying mechanisms remain unclear. We aimed to examine the association of sleep duration with cognitive performance and structural brain differences using magnetic resonance imaging (MRI). Methods: Within the UK Biobank, 43,255 dementia‐free participants (aged ≥44, 52.0% female) were included. Self‐reported sleep duration (hours/day) was recorded following a structured questionnaire and trichotomized as short (≤5), normal (6‐8), and long (≥9) sleep. Cognitive functioning (including fluid intelligence, pairs matching, reaction time, and numeric memory) was evaluated using a touchscreen test battery. MRI scans were performed, and total and regional brain volumes (including white matter, gray matter, and hippocampus), and white matter hyperintensities (WMH) were measured. Data on lifestyle factors and medical conditions were collected. Data were analyzed using linear regression. Results: Of all participants, 2092 (4.8%) had short, 38,041 (87.9%) had normal, and 3122 (7.2%) had long sleep. In multi‐adjusted linear regression, compared with normal sleep duration, both short (β: ‐0.14, 95%, CI: ‐0.19 to ‐0.10) and long (β: ‐0.06, 95% CI: ‐0.10 to ‐0.03) sleep were related to poorer performance in fluid intelligence. Long sleep was also associated with poorer numeric memory (β: ‐0.06, 95% CI: ‐0.10 to ‐0.01). In MRI data analyses, compared with normal sleep duration, short sleep was related to a smaller hippocampus volume (β: ‐0.05, 95% CI: ‐0.09 to ‐0.01), while long sleep was associated with smaller total brain (β: ‐4.51, 95% CI: ‐6.82 to ‐2.21), gray matter (β: ‐3.32 95% CI: ‐4.70 to ‐1.94), and hippocampus (β: ‐0.06, 95% CI ‐0.09 to ‐0.02) volumes, but greater WMH (β: 0.05, 95% CI: 0.01 to 0.08), after adjusting for confounders. Conclusions: Short and long sleep durations are associated with poorer cognitive performance in different domains. Short sleep may indicate neurodegeneration, and long sleep may implicate both neurodegenerative and vascular changes in the brain. [ABSTRACT FROM AUTHOR]

Background: Falls are common among older adults with dementia, but the timing of incident injurious falls at different stages of dementia diagnosis is unclear. We aimed to examine injurious falls before, during, and after dementia diagnosis to detect when the occurrence of falls starts to increase prior to dementia onset, when people with dementia are at highest risk of falls, and which factors are associated with falls among people with dementia. Method: This study included 4874 participants aged ≥55, consisting of 2437 incident dementia cases detected in a dementia‐free cohort from the Swedish Twin Registry and 2437 1:1 matched (i.e., same birth year and sex) non‐demented controls from the cohort. Dementia diagnosis and date of onset were identified from the National Patient Registry (NPR) and the Swedish Cause of Death Register. Information on injurious falls, including date of occurrence and history of chronic disease, was obtained from the NPR. Data on demographics, lifestyle, and anthropometrics were collected through a self‐reported questionnaire. Data were analyzed using conditional Poisson regression and generalized estimating equation (GEE) models. Result: In Poisson regression analysis, the adjusted incidence rates of injurious falls among dementia cases and controls were similar (around 3.65‐9.08 per 1,000 person‐years) in the 6‐10 years preceding dementia diagnosis. Compared to controls, the incidence of falls in dementia cases started to increase beginning 5 years prior to dementia diagnosis (incidence rate ratio [IRR] 1.50, 95% confidence interval [CI] 1.11‐2.03), reaching a peak (IRR 3.37, 95% CI 2.85–3.97) in the year of dementia diagnosis, and declining rapidly 3 years after dementia diagnosis (IRR 1.38, 95% CI 1.05–1.79). In multi‐adjusted GEE models, alcohol consumption, living alone, and stroke were significantly associated with incident falls among people with dementia. Conclusion: Compared to dementia‐free people, those with dementia have a greater incidence of injurious falls that increases in the 5 years leading up to dementia diagnosis and peaks during the year of dementia diagnosis. Alcohol consumption, living alone, and stroke may predict falls among people with dementia. Our findings highlight the importance of a tailored preventive strategy against falls among people with dementia, especially in the diagnosis stage. [ABSTRACT FROM AUTHOR]

Background: High cognitive reserve (CR) has been related to a decreased dementia risk, but the association between CR and survival with independence is unknown. We examined whether lifelong CR accumulation is associated with disability‐free survival and explored the extent to which cognitive function mediates this association. Method: Within the Rush Memory and Aging Project, 1,633 dementia‐ and disability‐free participants (mean age: 79.3 years) were followed annually for up to 22 years to detect disability and deaths. A lifelong CR indicator was derived based on information about education, early‐life, mid‐life, and late‐life cognitive activities, and late‐life social activity, and categorized into tertiles (low, moderate, and high). Disability was assessed annually in terms of participants' ability to conduct activities of daily living and survival status was observed during the follow‐up period. Global cognitive function was assessed annually with a battery of 19 tests. Data were analyzed using Cox models, Laplace regression, and generalized structural equation models. Result: During the follow‐up (median: 4.35 years, interquartile range: 2.01 to 7.98 years), 1,079 (64.6%) participants died or developed disability. In multi‐adjusted Cox models, CR score was does‐dependently associated with disability/death (hazard ratio [HR] 0.96, confidence interval [CI] 0.93–0.99). Compared to low CR, the multi‐adjusted HR (95% CI) of high CR was 0.82 (0.70–0.95) for disability/death. In Laplace regression, the median disability‐free survival time was prolonged by 0.17 (95% CI 0.05–0.30) years per unit higher CR score, and 0.99 (95% CI 0.28–1.71) years for participants with high CR compared to low CR. In mediation analysis, cognitive function mediated 35.7% of the association between CR and disability‐free survival. Conclusion: High lifelong CR is associated with prolonged disability‐free survival, and cognitive function mediates about one‐third of this association. [ABSTRACT FROM AUTHOR]

Background: The relation of poor pulmonary function (PF) to cognitive trajectories and the mechanisms behind the relation remains unclear. We aimed to investigate the association of poor PF with cognitive decline in different domains and structural brain volumes. Method: Within Rush Memory and Aging Project, 1377 dementia‐free subjects were followed up to 21 years. PF was assessed with a composite score (tertiled as the lowest, middle, and highest) based on peak expiratory flow, forced expiratory volume in 1 second, and forced vital capacity measured at baseline. Episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually constructed from 19 cognitive tests. A sub‐sample of the participants (n=373) underwent brain magnetic resonance imaging (MRI), and total, regional brain (white matter, gray matter) and white matter hyperintensities volumes were assessed. Data were analyzed using linear mixed‐effect models and linear regression models. Result: At baseline, the PF score was ranged from ‐2.36 to 3.47. In multi‐adjusted mixed‐effect model, compared with the highest PF, the lowest PF was related to decline in global cognition (β=‐0.039, 95% CI: ‐0.054 to ‐0.024), episodic memory (β= ‐0.053, 95% CI: ‐0.072 to ‐0.033), semantic memory (β= ‐0.032, 95% CI: ‐0.048 to ‐0.015), working memory (β= ‐0.028, 95%CI: ‐0.041 to ‐0.014), visuospatial ability (β= ‐0.027, 95% CI: ‐0.042 to ‐0.013), and perceptual speed (β= ‐0.038, 95% CI: ‐0.053 to ‐0.022). In MRI data analysis, the lowest PF was associated with smaller volumes of total brain (β= ‐29.61, 95% CI: ‐45.25 to ‐13.98), white matter (β= ‐12.62, 95% CI: ‐23.56 to ‐1.68), and gray matter (β= ‐16.95, 95% CI: ‐28.93 to ‐4.96), but greater white matter hyperintensities (β= 0.214, 95% CI: 0.094 to 0.334), compared to the highest PF. Conclusion: Low PF accelerates cognitive decline in global cognition, episodic memory, working memory, semantic memory, visuospatial ability and perceptual speed. Neurodegeneration and vascular lesions in the brain may underlie the association of PF with cognitive decline. [ABSTRACT FROM AUTHOR]

Background: The association of pulmonary function (PF) with mild cognitive impairment (MCI) and its underlying mechanisms remain unclear. We examined the association of PF with MCI and brain pathologies. Method: Within the Rush Memory and Aging Project, the 1025 no cognitive impairment (NCI) participants (mean age: 79.41±7.77 years) were followed for up to 21 years to detect incident MCI. PF was assessed with a composite score based on forced vital capacity, forced expiratory volume in 1s, and peak expiratory flow measured at baseline, and further divided into tertiles (i.e., lowest, middle, and highest). MCI was diagnosed following standard criteria. During the follow‐up, 396 participants died and underwent autopsies for neuropathological assessment (including Alzheimer's disease [AD], and vascular brain pathologies). Data were analyzed using Cox regression, Laplace regression, and Logistic regression. Result: During the follow‐up (median 7 years, interquartile range 4‐10 years), 461 participants developed MCI. Compared to the highest PF, the multi‐adjusted HR (95% CI) was 2.07 (1.55‐2.78) for MCI. The median time from NCI to MCI development was 4.05 (95% CI: 2.78‐5.31) years shorter in people with the lowest PF than those with the highest PF. In the pathological data analysis, the lowest PF was significantly related to higher AD pathology (odds ratio [OR]: 1.45, 95% CI: 1.29‐1.62) and vascular brain pathologies (OR: 3.47, 95% CI: 1.50‐8.03) compared to the highest PF. Conclusion: The lowest PF is associated with a 2‐fold risk of MCI and accelerates progression from NCI to MCI by more than 4 years. Both neurodegenerative and vascular mechanisms may underlie this association. [ABSTRACT FROM AUTHOR]