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BACKGROUND AND OBJECTIVES: Previous randomized controlled trials and longitudinal studies have indicated that ongoing antihypertensive use in late life reduces all-cause dementia risk, but the specific impact on Alzheimer dementia (AD) and non-AD risk remains unclear. This study investigates whether previous hypertension or antihypertensive use modifies AD or non-AD risk in late life and the ideal blood pressure (BP) for risk reduction in a diverse consortium of cohort studies. METHODS: This individual participant data meta-analysis included community-based longitudinal studies of aging from a preexisting consortium. The main outcomes were risk of developing AD and non-AD. The main exposures were hypertension history/antihypertensive use and baseline systolic BP/diastolic BP. Mixed-effects Cox proportional hazards models were used to assess risk and natural splines were applied to model the relationship between BP and the dementia outcomes. The main model controlled for age, age2, sex, education, ethnoracial group, and study cohort. Supplementary analyses included a fully adjusted model, an analysis restricting to those with >5 years of follow-up and models that examined the moderating effect of age, sex, and ethnoracial group. RESULTS: There were 31,250 participants from 14 nations in the analysis (41% male) with a mean baseline age of 72 (SD 7.5, range 60-110) years. Participants with untreated hypertension had a 36% (hazard ratio [HR] 1.36, 95% CI 1.01-1.83, p = 0.0406) and 42% (HR 1.42, 95% CI 1.08-1.87, p = 0.0135) increased risk of AD compared with "healthy controls" and those with treated hypertension, respectively. Compared with "healthy controls" both those with treated (HR 1.29, 95% CI 1.03-1.60, p = 0.0267) and untreated hypertension (HR 1.69, 95% CI 1.19-2.40, p = 0.0032) had greater non-AD risk, but there was no difference between the treated and untreated groups. Baseline diastolic BP had a significant U-shaped relationship (p = 0.0227) with non-AD risk in an analysis restricted to those with 5-year follow-up, but otherwise there was no significant relationship between baseline BP and either AD or non-AD risk. DISCUSSION: Antihypertensive use was associated with decreased AD but not non-AD risk throughout late life. This suggests that treating hypertension throughout late life continues to be crucial in AD risk mitigation. A single measure of BP was not associated with AD risk, but DBP may have a U-shaped relationship with non-AD risk over longer periods in late life.
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Doença de Alzheimer , Anti-Hipertensivos , Pressão Sanguínea , Demência , Hipertensão , Humanos , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/complicações , Idoso , Pressão Sanguínea/efeitos dos fármacos , Demência/epidemiologia , Masculino , Feminino , Idoso de 80 Anos ou mais , Estudos Longitudinais , Fatores de RiscoRESUMO
PURPOSE: To identify longitudinal retinal layer thickness changes in normal eyes of cognitively healthy elderly people. METHODS: Post hoc analysis was performed on 57 cognitively healthy elderly participants from the population-based Korean Longitudinal Study on Health and Aging and Korean Longitudinal Study on Cognitive Aging and Dementia cohort studies who underwent baseline and final optical coherence tomography scans. The peripapillary retinal nerve fiber layer, subfoveal choroid, and average retinal layer thickness at four quadrant (nasal, temporal, superior, and inferior) points 1 mm, 2 mm, and 3 mm from the center of the fovea were measured. RESULTS: The mean age of subjects was 75.1 years and the mean follow-up period was 55.9 months. Among the analyzed retinal layers, both the ganglion cell-inner plexiform layer and the outer nuclear layer at all 1 mm, 2 mm, and 3 mm points showed a statistically significant decrease in thickness at the final visit compared with baseline. The annual decrease rates were -1.2 µm/year at 1 mm (total -6.6%), -1.3 µm/year at 2 mm (total -8.4%), and -1.1 µm/year at 3 mm (total -9.7%) for ganglion cell-inner plexiform layer and -0.6 µm/year at 1 mm (total -4.2%), -0.5 µm/year at 2 mm (total -3.9%), and -0.4 µm/year at 3 mm (total -4.1%) for outer nuclear layer. CONCLUSION: Aging plays a significant role in the reduction of ganglion cell-inner plexiform layer and outer nuclear layer thicknesses in cognitively healthy elderly individuals.
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Fibras Nervosas , Células Ganglionares da Retina , Tomografia de Coerência Óptica , Humanos , Idoso , Feminino , Masculino , Tomografia de Coerência Óptica/métodos , Células Ganglionares da Retina/patologia , Idoso de 80 Anos ou mais , Seguimentos , Cognição/fisiologia , Retina/diagnóstico por imagem , Retina/anatomia & histologia , Estudos Longitudinais , República da Coreia , Envelhecimento/fisiologiaRESUMO
OBJECTIVE: White matter hyperintensities (WMH) are common among the elderly. Although WMH play a key role in lowering the threshold for the clinical expression of dementia in Alzheimer's disease (AD)-related pathology, the clinical significance of their location is not fully understood. This study aimed to investigate the association between WMH and cognitive function according to the location of WMH in AD. METHODS: Subjects underwent clinical evaluations including volumetric brain magnetic resonance imaging study and neuropsychological tests using the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet. WMH were calculated using automated quantification method. According to the distance from the lateral ventricular surface, WMH within 3 mm, WMH within 3-13 mm, and WMH over 13 mm were classified as juxtaventricular WMH (JVWMH), periventricular WMH (PVWMH), and deep WMH (DWMH), respectively. RESULTS: Total WMH volume was associated with poor performance in categorical verbal fluency test (ß=-0.197, p=0.035). JVWMH volume was associated with poor performances on categorical verbal fluency test (ß=-0.201, p=0.032) and forward digit span test (ß= -0.250, p=0.012). PVWMH volume was associated with poor performances on categorical verbal fluency test (ß=-0.185, p=0.042) and word list memory test (ß=-0.165, p=0.042), whereas DWMH volume showed no association with cognitive tests. PVWMH volume were also related to Clinical Dementia Rating Scale Sum of Boxes score (ß=0.180, p=0.026). CONCLUSION: WMH appear to exhibit different associations with the severity of dementia and cognitive impairment according to the distance from ventricle surface in AD.
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OBJECTIVE: To address the gap in timely diagnosis of dementia due to limited screening tools, we investigated the validity and reliability of the Hellocog, computerized neuropsychological test based on tablets for screening dementia. The higher the probability score on the Hellocog, the higher the likelihood of dementia. METHODS: This study included 100 patients with dementia and 100 individuals with normal cognition who were aged 60 years or older and free of other major psychiatric, neurological, or medical conditions. They administered the Hellocog on a tablet under the supervision of a neuropsychologist. To determine test-retest reliability, 20 took the Hellocog again after 4 weeks. Diagnostic performance was assessed using the receiver operator characteristics (ROC) analysis. RESULTS: The Hellocog showed adequate internal consistency (Cronbach's alpha=0.69) and good test-retest reliability (intraclass correlation coefficient=0.86, p<0.001). Participants with dementia scored higher on the Hellocog than those with normal cognition (p<0.001), confirming its high criterion validity. Strong correlations with the Mini-Mental Status Examination (MMSE) score and the total score of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-TS) highlight the concurrent validity of the Hellocog. The area under the ROC curve for dementia of the Hellocog was excellent (0.971) and comparable to that of the MMSE and CERAD-TS. The sensitivity and specificity for dementia were 0.945 and 0.872%, respectively, which were slightly better than those of the MMSE and CERAD-TS. CONCLUSION: Hellocog stands out as a valid and reliable tool for self-administered dementia screening, with promise for improving early detection of dementia.
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Gamma entrainment through sensory stimulation has the potential to reduce the pathology of Alzheimer's disease in mouse models. However, clinical trials in Alzheimer's disease (AD) patients have yielded inconsistent results, necessitating further investigation. This single-center pre-post intervention study aims to explore the influence of white matter microstructural integrity on gamma rhythm propagation from the visual cortex to AD-affected regions in 31 cognitively normal volunteers aged ≥ 65. Gamma rhythm propagation induced by optimal FLS was measured. Diffusion tensor imaging was employed to assess the integrity of white matter tracts of interest. After excluding 5 participants with a deficit in steady-state visually evoked potentials, 26 participants were included in the final analysis. In the linear regression analyses, gamma entrainment was identified as a significant predictor of gamma propagation (p < 0.001). Furthermore, the study identified white matter microstructural integrity as a significant predictor of gamma propagation by flickering light stimulation (p < 0.05), which was specific to tracts that connect occipital and temporal or frontal regions. These findings indicate that, despite robust entrainment of gamma rhythms in the visual cortex, their propagation to other regions may be impaired if the microstructural integrity of the white matter tracts connecting the visual cortex to other areas is compromised. Consequently, our findings have expanded our understanding of the prerequisites for effective gamma entrainment and suggest that future clinical trials utilizing visual stimulation for gamma entrainment should consider white matter tract microstructural integrity for candidate selection and outcome analysis.
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BACKGROUND: Spatial normalization to a standardized brain template is a crucial step in magnetic resonance imaging (MRI) studies. Brain templates made from sufficient sample size have low brain variability, improving the accuracy of spatial normalization. Using population-specific template improves accuracy of spatial normalization because brain morphology varies according to ethnicity and age. METHODS: We constructed a brain template of normal Korean elderly (KNE200) using MRI scans 100 male and 100 female aged over 60 years old with normal cognition. We compared the deformation after spatial normalization of the KNE200 template to that of the KNE96, constructed from 96 cognitively normal elderly Koreans and to that of the brain template (OCF), constructed from 434 non-demented older Caucasians to examine the effect of sample size and ethnicity on the accuracy of brain template, respectively. We spatially normalized the MRI scans of elderly Koreans and quantified the amount of deformations associated with spatial normalization using the magnitude of displacement and volumetric changes of voxels. RESULTS: The KNE200 yielded significantly less displacement and volumetric change in the parahippocampal gyrus, medial and posterior orbital gyrus, fusiform gyrus, gyrus rectus, cerebellum and vermis than the KNE96. The KNE200 also yielded much less displacement in the cerebellum, vermis, hippocampus, parahippocampal gyrus and thalamus and much less volumetric change in the cerebellum, vermis, hippocampus and parahippocampal gyrus than the OCF. CONCLUSION: KNE200 had the better accuracy than the KNE96 due to the larger sample size and was far accurate than the template constructed from elderly Caucasians in elderly Koreans.
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Encéfalo , Imageamento por Ressonância Magnética , Humanos , Feminino , Imageamento por Ressonância Magnética/métodos , Masculino , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/anatomia & histologia , Pessoa de Meia-Idade , República da Coreia , Povo Asiático , Idoso de 80 Anos ou mais , Envelhecimento , Processamento de Imagem Assistida por Computador/métodos , População do Leste AsiáticoRESUMO
Differentiating clinical stages based solely on positive findings from amyloid PET is challenging. We aimed to investigate the neuroanatomical characteristics at the whole-brain level that differentiate prodromal Alzheimer's disease (AD) from cognitively unimpaired amyloid-positive individuals (CU A+) in relation to amyloid deposition and regional atrophy. We included 45 CU A+ participants and 135 participants with amyloid-positive prodromal AD matched 1:3 by age, sex, and education. All participants underwent 18F-florbetaben positron emission tomography and 3D structural T1-weighted magnetic resonance imaging. We compared the standardized uptake value ratios (SUVRs) and volumes in 80 regions of interest (ROIs) between CU A+ and prodromal AD groups using independent t-tests, and employed the least absolute selection and shrinkage operator (LASSO) logistic regression model to identify ROIs associated with prodromal AD in relation to amyloid deposition, regional atrophy, and their interaction. After applying False Discovery Rate correction at < 0.1, there were no differences in global and regional SUVR between CU A+ and prodromal AD groups. Regional volume differences between the two groups were observed in the amygdala, hippocampus, entorhinal cortex, insula, parahippocampal gyrus, and inferior temporal and parietal cortices. LASSO logistic regression model showed significant associations between prodromal AD and atrophy in the entorhinal cortex, inferior parietal cortex, both amygdalae, and left hippocampus. The mean SUVR in the right superior parietal cortex (beta coefficient = 0.0172) and its interaction with the regional volume (0.0672) were also selected in the LASSO model. The mean SUVR in the right superior parietal cortex was associated with an increased likelihood of prodromal AD (Odds ratio [OR] 1.602, p = 0.014), particularly in participants with lower regional volume (OR 3.389, p < 0.001). Only regional volume differences, not amyloid deposition, were observed between CU A+ and prodromal AD. The reduced volume in the superior parietal cortex may play a significant role in the progression to prodromal AD through its interaction with amyloid deposition in that region.
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Doença de Alzheimer , Compostos de Anilina , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Sintomas Prodrômicos , Estilbenos , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Masculino , Feminino , Idoso , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Pessoa de Meia-Idade , Atrofia , Peptídeos beta-Amiloides/metabolismo , Cognição , Idoso de 80 Anos ou mais , Amiloide/metabolismoRESUMO
Background: Impaired glymphatic flow on the Alzheimer's disease (AD) spectrum may be evaluated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). Objective: We aimed to validate impaired glymphatic flow and explore its association with gray matter volume, cognitive status, and cerebral amyloid deposition on the AD spectrum. Methods: 80 participants (mean age, 76.9±8.5 years; 57 women) with AD (nâ=â65) and cognitively normal (CN) (nâ=â15) who underwent 3T brain MRI including DTI and/or amyloid PET were included. After adjusting for age, sex, apolipoprotein E status, and burden of white matter hyperintensities, the ALPS-index was compared according to the AD spectrum. The association between the ALPS-index and gray matter volume, cognitive status, and quantitative amyloid from PET was assessed. Results: The ALPS-index in the AD was significantly lower (mean, 1.476; 95% CI, 1.395-1.556) than in the CN (1.784;1.615-1.952; pâ=â0.026). Volumes of the entorhinal cortex, hippocampus, temporal pole, and primary motor cortex showed significant associations with the ALPS-index (all, pâ<â0.05). There was a positive correlation between the ALPS-index and MMSE score (partial râ=â0.435; pâ<â0.001), but there was no significant correlation between the ALPS-index and amyloid SUVRs (all, pâ>â0.05). Conclusions: Decreased glymphatic flow measured by DTI-ALPS in AD may serve as a marker of neurodegeneration correlating with structural atrophy and cognitive decline.
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Doença de Alzheimer , Disfunção Cognitiva , Imagem de Tensor de Difusão , Sistema Glinfático , Substância Cinzenta , Tomografia por Emissão de Pósitrons , Humanos , Feminino , Masculino , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Idoso , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Substância Cinzenta/metabolismo , Sistema Glinfático/diagnóstico por imagem , Sistema Glinfático/patologia , Sistema Glinfático/metabolismo , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/metabolismoRESUMO
INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.
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Demência , Estilo de Vida , Humanos , Demência/epidemiologia , Masculino , Feminino , Fatores de Risco , Idoso , Estudos Prospectivos , IncidênciaRESUMO
Background and objectives: Musculoskeletal (MSK) pain significantly impacts physical activity and quality of life in older adults, potentially influencing mortality. This study explored the relationship between MSK pain, physical activity, muscle mass, and mortality among older adults. Material and Methods: We studied 1000 participants in the Korean Longitudinal Study on Health and Aging (KLoSHA), a prospective, population-based cohort study of people aged 65 years or older. Survival status was tracked over a 5-year period. Correlations between low back pain (LBP), knee pain, regular exercise, appendicular skeletal muscle mass (ASM), and other variables were analyzed. Logistic regression analyses were used to identify independent risk factors for mortality. Results: Of the total participants, 829 (82.9%) survived over a 5-year period. Survivors tended to be younger, had a higher BMI, and were more active in regular exercise. In contrast, non-survivors exhibited a higher prevalence of both LBP and knee pain, along with increased instances of multiple MSK pains. Lower ASM correlated moderately with LBP and knee pain, whereas higher ASM was associated with regular exercise. There was a moderate correlation between LBP and knee pain, both of which were associated with a lack of regular exercise. Age, sex, ASM, and regular exercise were significant predictors, even though MSK pain itself did not directly predict all-cause mortality. Conclusions: This study demonstrated the independent association between ASM, regular exercise, and mortality. Although MSK pain did not directly correlate with all-cause mortality, the non-survivor group had higher levels of both single and multiple MSK pains. Recognizing the interplay of MSK pain, physical activity, and muscle mass for older adults, the research underscores the need for holistic strategies to enhance health outcomes in older individuals with MSK pain.
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Dor Lombar , Dor Musculoesquelética , Humanos , Idoso , Estudos Longitudinais , Estudos de Coortes , Qualidade de Vida , Estudos Prospectivos , Envelhecimento/fisiologia , Exercício Físico , República da Coreia/epidemiologia , MúsculosRESUMO
BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been suggested as a cognitive enhancing agent, though their effect is doubtful. We aimed to examine the effect of n-3 PUFA on the cognitive function of middle-aged or older adults without dementia. METHODS: We reviewed randomized controlled trials of individuals aged 40 years or older. We systematically searched PubMed/MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Library databases. We used the restricted cubic splines model for non-linear dose-response meta-analysis in terms of the standardized mean difference with 95% confidence intervals. RESULTS: The current meta-analysis on 24 studies (n 9660; follow-up 3 to 36 months) found that the beneficial effect on executive function demonstrates an upward trend within the initial 12 months of intervention. This effect is prominently observed with a daily intake surpassing 500 mg of n-3 PUFA and up to 420 mg of eicosapentaenoic acid (EPA). Furthermore, these trends exhibit heightened significance in regions where the levels of blood docosahexaenoic acid (DHA) + EPA are not very low. CONCLUSIONS: Supplementation of n-3 PUFA may confer potential benefits to executive function among the middle-aged and elderly demographic, particularly in individuals whose dietary DHA + EPA level is not substantially diminished.
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Cognição , Ácidos Graxos Ômega-3 , Humanos , Ácidos Graxos Ômega-3/administração & dosagem , Cognição/efeitos dos fármacos , Cognição/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso , Pessoa de Meia-Idade , Adulto , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Demência/tratamento farmacológicoRESUMO
PURPOSE: There is increasing evidence that promoting physical activity can prevent sarcopenia. However, physical activity (PA) decreases with age, and the impact of PA intensity on health is unclear. This study investigated the relationship between the level of PA and sarcopenia, and the association between PA levels and mortality in patients with and without sarcopenia. METHODS: Data were derived from the Korean Longitudinal Study on Health and Aging. PA was classified as sedentary behavior, light PA, or moderate-to-vigorous PA. Each PA level was subdivided based on the median time spent engaged in that activity, yielding eight PA profiles. Logistic regression and Cox proportional hazard models were used to investigate the association between PA level and sarcopenia, and between PA profiles and mortality. RESULTS: This study included 620 participants (50.2% women; mean age 75.7 ± 7.5 years), of whom 130 (21.0%) participants were identified sarcopenia. During follow-up (mean 10.9 ± 4.1 years), 264 (42.6%) participants died. Overall, sarcopenic participants were less physically active than non-sarcopenic participants. After multivariate adjustment, more sedentary behavior and less moderate-to-vigorous PA were associated with sarcopenia and all related variables, except muscle mass. Compared with the reference, non-sarcopenic participants with lower sedentary behavior and concomitantly higher moderate-to-vigorous PA had significantly lower hazard ratios for mortality, while higher light PA reduced mortality in sarcopenic participants regardless of time spent engaged in sedentary behavior or moderate-to-vigorous PA. CONCLUSIONS: PA, especially sedentary behavior and moderate-to-vigorous PA, was associated with sarcopenia and related variables, but the level of PA that prevented death differed according to sarcopenia status. Our findings may help determine the optimal intensity and amount of PA.
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Exercício Físico , Sarcopenia , Comportamento Sedentário , Humanos , Sarcopenia/mortalidade , Feminino , Masculino , Idoso , Estudos Longitudinais , República da Coreia/epidemiologia , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Modelos de Riscos Proporcionais , Mortalidade , Modelos LogísticosRESUMO
BACKGROUND: The relationship between depression and the risk of multimorbidity progression has rarely been studied in older adults. This study was aimed to determine whether depression is associated with progression in the severity and complexity of multimorbidity, considering the influence of depression's severity and subtype. METHODS: As a part of the Korean Longitudinal Study on Cognitive Aging and Dementia, this population-based cohort study followed a random sample of community-dwelling Koreans aged 60 and older for 8 years at 2-year intervals starting in 2010. Participants included those who completed mood and multimorbidity assessments and did not exhibit complex multimorbidity at the study's outset. Depression was assessed using the Geriatric Depression Scale, while multimorbidity was evaluated using the Cumulative Illness Rating Scale. The study quantified multimorbidity complexity by counting affected body systems and measured multimorbidity severity by averaging scores across 14 body systems. FINDINGS: The 2,486 participants (age = 69.1 ± 6.5 years, 57.6% women) were followed for 5.9 ± 2.4 years. Linear mixed models revealed that participants with depression had a faster increase in multimorbidity complexity score (ß = .065, SE = 0.019, p = 0.001) than those without depression, but a comparable increase in multimorbidity severity score (ß = .001, SE = .009, p = 0.870) to those without depression. Cox proportional hazard models revealed that depression was associated with the risk of developing highly complex multimorbidity affecting five or more body systems, particularly in severe or anhedonic depression. INTERPRETATION: Depression was associated with the worsening of multimorbidity in Korean older adults, particularly when severe or anhedonic. Early screening and management of depression may help to reduce the burden of multimorbidity in older adults.
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Depressão , Progressão da Doença , Multimorbidade , Humanos , Feminino , Masculino , Idoso , República da Coreia/epidemiologia , Depressão/epidemiologia , Estudos Longitudinais , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Vida Independente/estatística & dados numéricos , Estudos de CoortesRESUMO
INTRODUCTION: White matter hyperintensities (WMHs) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well documented in populations of different ethnicities and/or from different geographical regions. METHODS: We investigated how WMHs were associated with vascular risk factors and cognition in both Whites and Asians, using data from five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1946). WMH volumes (whole brain, periventricular, and deep) were quantified with UBO Detector and harmonized using the ComBat model. We also harmonized various vascular risk factors and scores for global cognition and individual cognitive domains. RESULTS: Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake, and insufficient physical activity. Hypertension and stroke had stronger associations with WMH volumes in Whites than in Asians. No associations between WMH volumes and cognitive performance were found after correction for multiple testing. CONCLUSION: The current study highlights ethnic differences in the contributions of vascular risk factors to WMHs.
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AIM: Brain volume is influenced by several factors that can change throughout the day. In addition, most of these factors are influenced by sleep quality. This study investigated diurnal variation in brain volume and its relation to overnight sleep quality. METHODS: We enrolled 1,003 healthy Koreans without any psychiatric disorders aged 60 years or older. We assessed sleep quality and average wake time using the Pittsburgh Sleep Quality Index, and divided sleep quality into good, moderate, and poor groups. We estimated the whole and regional brain volumes from three-dimensional T1-weighted brain MRI scans. We divided the interval between average wake-up time and MRI acquisition time (INT) into tertile groups: short (INT1), medium (INT2), and long (INT3). RESULTS: Whole and regional brain volumes showed no significance with respect to INT. However, the `interaction between INT and sleep quality showed significance for whole brain, cerebral gray matter, and cerebrospinal fluid volumes (p < .05). The INT2 group showed significantly lower volumes of whole brain, whole gray matter, cerebral gray matter, cortical gray matter, subcortical gray matter, and cerebrospinal fluid than the INT1 and INT3 groups only in the individuals with good sleep quality. CONCLUSION: Human brain volume changes significantly within a day associated with overnight sleep in the individuals with good sleep quality.
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Encéfalo , Qualidade do Sono , Humanos , Idoso , Estudos Transversais , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: High gait variability is associated with neurodegeneration and cognitive impairments and is predictive of cognitive impairment and dementia. The objective of this study was to identify cortical or subcortical structures of the brain shared by gait variability measured using a body-worn tri-axial accelerometer (TAA) and cognitive function. METHODS: This study is a part of a larger population-based cohort study on cognitive aging and dementia. The study included 207 participants without dementia, with a mean age of 72.6, and 45.4% of them are females. We conducted standardized diagnostic interview including a detailed medical history, physical and neurological examinations, and laboratory tests for cognitive impairment. We obtained gait variability during walking using a body-worn TAA along and measured cortical thickness and subcortical volume from brain magnetic resonance (MR) images. We cross-sectionally investigated the cortical and subcortical neural structures associated with gait variability and the shared neural substrates of gait variability and cognitive function. RESULTS: Higher gait variability was associated with the lower cognitive function and thinner cortical gray matter but not smaller subcortical structures. Among the clusters exhibiting correlations with gait variability, one that included the inferior temporal, entorhinal, parahippocampal, fusiform, and lingual regions in the left hemisphere was also associated with global cognitive and verbal memory function. Mediation analysis results revealed that the cluster's cortical thickness played a mediating role in the association between gait variability and cognitive function. CONCLUSION: Gait variability and cognitive function may share neural substrates, specifically in regions related to memory and visuospatial navigation.
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Disfunção Cognitiva , Demência , Feminino , Humanos , Adulto , Masculino , Estudos de Coortes , Cognição , Marcha , Imageamento por Ressonância Magnética , Demência/complicações , Demência/diagnóstico por imagem , Demência/patologia , Testes NeuropsicológicosRESUMO
Objective: : To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer's dementia and cognitive decline. Methods: : In all, 20 participants with Alzheimer's dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. Results: : The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer's dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. Conclusion: : The higher the GR, the lower the prevalence of Alzheimer's dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer's dementia and cognitive decline.
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BACKGROUND: Integrating a joint approach to chronic disease management within the context of a couple has immense potential as a valuable strategy for both prevention and treatment. Although spousal concordance has been reported in specific chronic illnesses, the impact they cumulatively exert on a spouse in a longitudinal setting has not been investigated. We aimed to determine whether one's cumulative illness burden has a longitudinal impact on that of their spouse. METHODS: Data was acquired from a community-based prospective cohort that included Koreans aged 60 years and over, randomly sampled from 13 districts nationwide. Data from the baseline assessment (conducted from November 2010 to October 2012) up to the 8-year follow-up assessment was analyzed from October 2021 to November 2022. At the last assessment, partners of the index participants were invited, and we included 814 couples in the analysis after excluding 51 with incomplete variables. Chronic illness burden of the participants was measured by the Cumulative Illness Rating Scale (CIRS). Multivariable linear regression and causal mediation analysis were used to examine the longitudinal effects of index chronic illness burden at baseline and its change during follow-up on future index and spouse CIRS scores. RESULTS: Index participants were divided based on baseline CIRS scores (CIRS < 6 points, n = 555, mean [SD] age 66.3 [4.79] years, 43% women; CIRS ≥ 6 points, n = 259, mean [SD] age 67.7 [4.76] years, 36% women). The baseline index CIRS scores and change in index CIRS scores during follow-up were associated with the spouse CIRS scores (ß = 0.154 [SE: 0.039], p < 0.001 for baseline index CIRS; ß = 0.126 [SE: 0.041], p = 0.002 for change in index CIRS) at the 8-year follow-up assessment. Subgroup analysis found similar results only in the high CIRS group. The baseline index CIRS scores and change in index CIRS scores during follow-up had both direct and indirect effects on the spouse CIRS scores at the 8-year follow-up assessment. CONCLUSIONS: The severity and course of one's chronic illnesses had a significant effect on their spouse's future chronic illness particularly when it was severe. Management strategies for chronic diseases that are centered on couples may be more effective.
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Cônjuges , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Doença Crônica , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Texture analysis may capture subtle changes in the gray matter more sensitively than volumetric analysis. We aimed to investigate the patterns of neurodegeneration in semantic variant primary progressive aphasia (svPPA) and Alzheimer's disease (AD) by comparing the temporal gray matter texture and volume between cognitively normal controls and older adults with svPPA and AD. METHODS: We enrolled all participants from three university hospitals in Korea. We obtained T1-weighted magnetic resonance images and compared the gray matter texture and volume of regions of interest (ROIs) between the groups using analysis of variance with Bonferroni posthoc comparisons. We also developed models for classifying svPPA, AD and control groups using logistic regression analyses, and validated the models using receiver operator characteristics analysis. RESULTS: Compared to the AD group, the svPPA group showed lower volumes in five ROIs (bilateral temporal poles, and the left inferior, middle, and superior temporal cortices) and higher texture in these five ROIs and two additional ROIs (right inferior temporal and left entorhinal cortices). The performances of both texture- and volume-based models were good and comparable in classifying svPPA from normal cognition (mean area under the curve [AUC] = 0.914 for texture; mean AUC = 0.894 for volume). However, only the texture-based model achieved a good level of performance in classifying svPPA and AD (mean AUC = 0.775 for texture; mean AUC = 0.658 for volume). CONCLUSION: Texture may be a useful neuroimaging marker for early detection of svPPA in older adults and its differentiation from AD.
Assuntos
Doença de Alzheimer , Afasia Primária Progressiva , Humanos , Idoso , Doença de Alzheimer/diagnóstico , Semântica , Afasia Primária Progressiva/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
Importance: The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested. Objectives: To assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age >60 years) with dementia and the moderating factors of age, sex, and racial group. Data Source and Study Selection: Longitudinal, population-based studies of aging participating in the Cohort Studies of Memory in an International Consortium (COSMIC) group were included. Participants were individuals without dementia at baseline aged 60 to 110 years and were based in 15 different countries (US, Brazil, Australia, China, Korea, Singapore, Central African Republic, Republic of Congo, Nigeria, Germany, Spain, Italy, France, Sweden, and Greece). Data Extraction and Synthesis: Participants were grouped in 3 categories based on previous diagnosis of hypertension and baseline antihypertensive use: healthy controls, treated hypertension, and untreated hypertension. Baseline systolic BP (SBP) and diastolic BP (DBP) were treated as continuous variables. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data reporting guidelines. Main Outcomes and Measures: The key outcome was all-cause dementia. Mixed-effects Cox proportional hazards models were used to assess the associations between the exposures and the key outcome variable. The association between dementia and baseline BP was modeled using nonlinear natural splines. The main analysis was a partially adjusted Cox proportional hazards model controlling for age, age squared, sex, education, racial group, and a random effect for study. Sensitivity analyses included a fully adjusted analysis, a restricted analysis of those individuals with more than 5 years of follow-up data, and models examining the moderating factors of age, sex, and racial group. Results: The analysis included 17 studies with 34â¯519 community dwelling older adults (20â¯160 [58.4%] female) with a mean (SD) age of 72.5 (7.5) years and a mean (SD) follow-up of 4.3 (4.3) years. In the main, partially adjusted analysis including 14 studies, individuals with untreated hypertension had a 42% increased risk of dementia compared with healthy controls (hazard ratio [HR], 1.42; 95% CI 1.15-1.76; P = .001) and 26% increased risk compared with individuals with treated hypertension (HR, 1.26; 95% CI, 1.03-1.53; P = .02). Individuals with treated hypertension had no significant increased dementia risk compared with healthy controls (HR, 1.13; 95% CI, 0.99-1.28; P = .07). The association of antihypertensive use or hypertension status with dementia did not vary with baseline BP. There was no significant association of baseline SBP or DBP with dementia risk in any of the analyses. There were no significant interactions with age, sex, or racial group for any of the analyses. Conclusions and Relevance: This individual patient data meta-analysis of longitudinal cohort studies found that antihypertensive use was associated with decreased dementia risk compared with individuals with untreated hypertension through all ages in late life. Individuals with treated hypertension had no increased risk of dementia compared with healthy controls.