Risk Factor For Cognitive Decline Research Articles

APOE4 and confluent WMH have a synergistic effect on episodic memory impairment in prodromal dementia

AbstractBackgroundWhite matter hyperintensities (WMH) are a known risk factor for cognitive decline (C.Puzo el. al. 2019). While the ε4 allele of apolipoprotein E gene (APOE4) is another risk factor for cognitive decline in concomitance with WMH (D.Tsuang et. al. 2013), it remains unclear how APOE4 affects the relationship between WMH and cognitive decline, specifically in the prodromal stage of dementia. Our objective was thus to determine how APOE4 moderates the relationship between WMH and cognition in prodromal dementia.Method216 participants with prodromal dementia underwent magnetic resonance imaging (MRI), neuropsychological testing (global and domain‐specific), cardiovascular risk factor assessments and APOE genotyping. Visual ratings for WMH as well as total and lobar WMH volumes were quantified. Moderation analysis was performed to determine the influence of APOE4 on the relationship between WMH and performance on global and domain‐specific cognitive measures (executive function, episodic memory, attention, language) in moderation analysis (Figure 1). The role of confluent and non‐confluent WMH subtype on cognition was additionally studied using moderation analysis and logistic regression (Figure 1).ResultAPOE4 carriers (n = 49) had poorer memory and higher global WMH (p = 0.04), temporal WMH (p = 0.01) and occipital WMH (p = 0.02) compared to APOE4 non‐carriers (n = 167). APOE4 strengthened the relationship between higher total WMH burden and worse episodic memory performance (Fig.2a). At the lobar WMH level, APOE4 strengthened associations between frontal, temporal, parietal and occipital WMH and episodic memory performance (Fig.2b, Fig.2c, Fig.2d, and Fig.2e) with large sized effects (β). APOE4 did not interact with either total or lobar WMH to predict worse cognition in other cognitive domains. Moreover, APOE4 strengthened the relationship between frontal WMH with episodic memory in the confluent WMH subgroup (Fig.2f). Logistic regression model showed memory impairment was 4.81 times more likely to develop in patients carrying APOE4 and with confluent WMH compared to APOE4 non‐carriers and those with non‐confluent WMH (OR 4.81, β 1.57, p<0.01).ConclusionThe impact of WMH on memory may be strongest in APOE4 carriers at the prodromal dementia stage. Clinicians targeting WMH would need to consider the APOE4 allele and WMH severity status to strategize cognitive interventions.

Amyloid PET in patients with carotid occlusive disease: Preliminary results of the AMYCODE study

AbstractBackgroundCarotid occlusive disease (COD) is a risk factor for cognitive decline. One of the proposed underlying mechanisms is that cerebral hypoperfusion may result in accelerated accumulation of amyloid‐β in the brain. We hypothesized that patients with longstanding, unilateral COD have an asymmetrical burden of cerebral amyloid‐β, with more amyloid‐β in the hemisphere ipsilateral to the COD than in the contralateral hemisphere.MethodThe AMYCODE study is a cross‐sectional observational study. Inclusion criterion is a unilateral occlusion of the internal carotid artery. Exclusion criteria are: a contralateral stenosis of > 70% and a history of vascular reconstructive surgery. All patients underwent a neuropsychological assessment, MRI‐scan and dynamic 18F Florbetaben positron emission tomography scan (PET). Global relative perfusion (R1) and binding potential (BPND) were determined from the PET‐images using PMOD and a simplified reference tissue model with the cerebellar grey matter as reference region. Distribution Volume ratio (DVR) was calculated as BPND + 1. We performed Wilcoxon signed‐rank tests to examine differences between hemispheres within subjects.ResultTo date, we included eight participants (seven males, age 66.1±7.3 years, MMSE score 28.1±2.0; inclusion ongoing, target n = 20). Mean global DVR was 1.03±0.03 in the ipsilateral hemisphere (i.e. side of the occlusion) and 1.04±0.02 in the contralateral hemisphere (p = 0.064). Mean global R1 was 0.89±0.06 in the ipsilateral hemisphere and 0.91±0.05 in the contralateral hemisphere (p = 0.033).ConclusionPreliminary analyses suggest that patients with unilateral COD had similar amyloid‐β distribution, despite lower cerebral perfusion in the hemisphere ipsilateral to the COD than in the contralateral hemisphere.

Effect of social isolation and loneliness on functional abilities mediated by cognition (E‐cog) in Mexican older adults during the first wave of COVID‐19 pandemic

AbstractBackgroundLoneliness and social isolation are known risk factors for cognitive decline; their effect in older adults (OA) after COVID‐19 lockdown is emerging.ObjectiveTo establish an association between loneliness with functional abilities mediated by cognition in Mexican OA during the first wave of the COVID‐19 pandemic.MethodCross‐sectional study derived from the cohort “The impact of COVID 19 on well‐being, cognition, and discrimination among older adults in the United States and Latin America”, which included 308 older adults recruited between March‐August 2020 whose cognition‐mediated functional abilities were determined with the Everyday Cognition Scale (E‐Cog) questionnaire. The presence of loneliness (The De Jong Gierveld Loneliness Scale) was a binomial variable. Univariate linear regression models were constructed to determine the association between loneliness, and E‐Cog (Ln) scores, which were later adjusted for potentially confounding variables like age and education. In addition, participants were categorized into tertiles of the global E‐Cog score with the following ranges: Tertile 1 (T1): 37.46 ‐46; Tertile 2 (T2): 46.01‐58 and Tertile 3 (T3): 58.01 or more and were compared using ANCOVA. Satistical analyses were conducted using SPSS version 25.0 for MAC (Chicago, IL, USA), figures were made with RStudio (R version 4.1.0, RStudio, Inc., Boston, MA)ResultThe mean age was 65.4 ± 7.9 years and 75.7% were women. The mean E‐Cog was 57.4 (SD: ± 19.1). 84% of participants (n:259) had loneliness. Those with less perception of loneliness had a better performance on E‐Cog by tertiles. The univariate linear model showed a positive and statistically significant association between loneliness and E‐Cog, adjusted by age, sex and education level (β 0.41, 95% CI: 0.22‐0.38, p: <0.01). This model explained 16.1% of the variability of the E‐Cog score.ConclusionOA with self‐reported loneliness had the worst performance in functional abilities mediated by cognition. These data suggest the need for increased vigilance of those who have loneliness due to its potential deleterious effect on cognitive function.

Social isolation, lifestyle and cognitive functioning in midlife and early‐late life: Implications for risk reduction of cognitive decline and dementia

AbstractBackgroundSocial isolation (SI) is considered a modifiable risk factor for cognitive decline and dementia, is associated with unhealthy lifestyle. We investigated independent and combined associations of SI and lifestyle with cognitive functioning (CF) in a midlife to early‐late life population without dementia. This informs developing more targeted preventive strategies against cognitive decline and dementia.MethodThe “LIfestyle for BRAin health” (LIBRA) score was computed for 6,203 baseline participants of the LIFE‐Adult‐Study, a population‐based German cohort. LIBRA is validated for dementia prediction in midlife to early‐late life populations, consisting of 12 modifiable factors (heart disease, kidney disease, diabetes, obesity, hypertension, hypercholesterolemia, alcohol consumption, smoking, physical inactivity, diet, depression, cognitive activity). Higher scores (‐5.9,+12.7) indicate “worse” lifestyle. SI was assessed with the short Lubben Social Network Scale (score < 12). For CF, we calculated a z‐standardized composite score of the Verbal Fluency Test, the Trail Making Test A and B. Associations of SI and LIBRA with CF were investigated using generalized linear modelling. Bootstrapped structural equation modelling (SEM) tested whether LIBRA mediated the association between SI and CF. Sampling weights were applied, variables z‐standardized for SEM.ResultsParticipants were M = 57.7 (SD = 12.0, range: 40‐79) years old; 50.7% were female; 15.8% were socially isolated. SI (β: ‐.17, 95%CI[‐.24,‐.10]; Wald = 21.45, p < .001) and a higher LIBRA score (β: ‐.03, 95%CI[‐.04,‐.02]; Wald = 31.49, p < .001) were independently associated with lower CF; there was no interaction (β: ‐.003, 95%CI[‐.03,.02]; Wald = 0.06, p = .814; Fig.1). Bootstrapped SEM (reps = 10,000; R² = .34) indicated that LIBRA partially mediated the association between SI and CF (IE = ‐.006, 95%CI[‐.008,‐.003], p < .001; proportion mediated = 8.5%; Fig.2).ConclusionCF is lower in socially isolated than socially integrated individuals without dementia. The CF difference can be partially attributed to modifiable health and lifestyle factors; however, only to a small extent. Therefore, public health initiatives aiming at preventing SI might be more effective in promoting good CF than lifestyle interventions in socially isolated individuals in midlife to early‐late life. This would likely benefit risk reduction of cognitive decline and dementia in later life.

Association of HbA1c trajectory and variability with cognitive function

AbstractBackgroundType 2 diabetes (T2D) is an important modifiable risk factor for cognitive decline, and increasing evidence suggests that worse glucose control, in addition to a diagnosis of T2D, may play a role in cognitive function in later life. Despite this increasing concern, evidence regarding the relative contributions of poor glucose control and higher glucose variability to cognitive dysfunction among individuals with overweight or obesity is limited, mostly due to lack of repeated measures in many studies.MethodLook AHEAD MIND Study participants, aged 45‐76 years at baseline (2001‐04) with T2D and overweight or obesity, were randomized to an intensive lifestyle intervention focused on weight loss or a diabetes support and education condition, which were discontinued after ∼10 years. HbA1c levels were evaluated at years 1‐4, 6, 8, and 10. Cognitive function was evaluated up to four times between years 8‐18 with a cognitive battery that assessed memory, attention, and executive function domains. Cognitive scores were binned into four groups based on relative timing of cognitive assessments (8‐9; 10‐11; 12‐14; and 15‐18 years). We classified HbA1c variability according to: Variability Independent of the Mean (VIM), Average Real Variability (ARV), and data‐driven latent trajectories. Mixed linear regression models for standardized composite cognitive scores were adjusted for: repeated measures, order of cognitive test, years from randomization, randomization arm, age, sex, race/ethnicity, years of education, CVD history, and APOE ε4.ResultFour HbA1c trajectories were identified: increasing, decreasing, stable‐high, and stable‐low. Composite cognitive scores were significantly lower for increasing, decreasing, and stable‐high HbA1c trajectories ‐compared to stable‐low HbA1c (Table). In multivariable analysis, higher baseline HbA1c, ARV, and VIM were associated with lower composite cognitive scores, and differences between groups were similar by years since randomization. Estimates for ARV and VIM were attenuated when adjusted for baseline HbA1c (not shown). Estimates were similar for tests from all cognitive domains, with little heterogeneity by randomization arm.ConclusionAmong individuals with T2D, higher HbA1c at baseline and greater HbA1c variability over 10 years were significantly associated with lower cognitive scores, suggesting that maintaining glucose control may be useful for the prevention of cognitive decline.

The analysis of fMRI complexity as a biomarker of cognitive decline compared to tau‐PET

AbstractBackgroundTau‐PET detects the neurofibrillary tangle pathology and is considered a biomarker of neuronal injury and cognitive decline. However, PET imaging has radiation exposure risks and is costly. Recently, brain entropy mapping based on rs‐fMRI has emerged as a brain functionality biomarker that indicates the complexity of BOLD signals. Various studies have implied that reduced brain entropy values correlate significantly with cognitive decline in Alzheimer’s disease. This study analyzes the effect of fMRI complexity as a biomarker of cognitive decline in AD compared to tau‐PET.MethodWe obtained the dataset for this study from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The dataset consisted of 147 subjects (age = 72.5±7.5, M/F = 60/87, CN/MCI/AD = 95/45/7) with a tau‐PET (tracer: 18F‐AV1451) and two fMRI scans. FMRI images underwent standard processing to generate Multi‐Scale Entropy (MSE) maps. We calculated parametric SUVR values based on cerebellar reference regions from tau‐PET images. To determine the ability of MSE and PET images as a risk factor of cognitive decline in AD, convolutional neural networks were used to classify individuals into CN or MCI/AD groups. Each classifier was trained separately with fMRI complexity images or SUVR images. These two models had the same network structures and hyperparameters. We performed a 5‐fold cross‐validation to evaluate each model.ResultThe classifier using fMRI‐MSE achieved an accuracy equivalent to that using tau‐PET (0.7823 vs. 0.7687). We also calculated the Area Under the ROC curve (AUC) to evaluate sensitivity and specificity and observed that the model using fMRI‐MSE achieved AUC of 0.7022, and that using tau‐PET resulted in AUC of 0.6889.ConclusionThe classification performance showed that use of fMRI‐MSE could potentially be an AD biomarker alternative to tau‐PET. Further studies with multisite, larger datasets are required to validate our preliminary results and provide more conclusive evidence.

Factors influencing cognitive decline in living alone by the residence characteristics: A longitudinal study

Purpose: This study aimed to identify the risk factors of cognitive decline in older adults living alone in local communities and to find cognitive nursing methods by the area of residence. Methods: The participants were 164 people living alone for 12 years. The data were analyzed using a generalized estimating equations method. Results: The following factors were identified as statistically significant predictors that increased cognitive decline in older adults living alone: 1) rural areas: age (odds ratio [OR]=1.02, 95% confidence interval [CI]=1.01~1.02), low education (OR=1.53, 95% CI=1.13~2.07), number of diseases (OR=1.07, 95% CI=1.01~1.14), 2) urban areas: women (OR=1.27, 95% CI=1.09~1.49), age (OR=1.02, 95% CI=1.01~1.03), low education (OR=1.26, 95% CI=1.14~1.40), body mass index (OR=0.98, 95% CI=0.96~0.99), instrumental activities of daily living (OR=1.02, 95% CI=1.00~1.04), depressive symptom (OR=1.14, 95% CI=1.03~1.25). Conclusion: The older adults who lived alone had different risk factors for cognitive decline depending on their areas of residence. Preventive management for cognitive decline should be presented according to the areas of residence among older adults living alone.

Detection of Insomnia and Its Relationship with Cognitive Impairment, Depression, and Quality of Life in Older Community-Dwelling Mexicans.

Sleep disturbances are one of the most frequent health problems in old age, among which insomnia stands out. It is characterized by difficulty falling asleep, staying asleep, frequent awakenings, or waking up too early and not having restful sleep, which may be a risk factor for cognitive impairment and depression, affecting functionality and quality of life. Insomnia is a very complex multifactorial problem that requires a multi- and interdisciplinary approach. However, it is frequently not diagnosed in older community-dwelling people, increasing the risk of psychological, cognitive, and quality of life alterations. The aim was to detect insomnia and its relationship with cognitive impairment, depression, and quality of life in older community-dwelling Mexicans. An analytical cross-sectional study was carried out in 107 older adults from Mexico City. The following screening instruments were applied: Athens Insomnia Scale, Mini-Mental State Examination, Geriatric Depression Scale, WHO Quality of Life Questionnaire WHOQoL-Bref, Pittsburgh Sleep Quality Inventory. The frequency of insomnia detected was 57% and its relationship with cognitive impairment, depression, and low quality of life was 31% (OR = 2.5, 95% CI, 1.1-6.6. p < 0.05), 41% (OR = 7.3, 95% CI, 2.3-22.9, p < 0.001), and 59% (OR = 2.5, 95% CI, 1.1-5.4, p < 0.05), respectively. Our findings suggest that insomnia is a frequent clinical disorder that is not diagnosed and a significant risk factor for cognitive decline, depression, and poor quality of life.

The relationship between long-term blood pressure variability and cortical thickness in older adults

High blood pressure variability (BPV) is a risk factor for cognitive decline and dementia, but its association with cortical thickness is not well understood. Here we use a topographical approach, to assess links between long-term BPV and cortical thickness in 478 (54% men at baseline) community dwelling older adults (70–88 years) from the ASPirin in Reducing Events in the Elderly NEURO sub-study. BPV was measured as average real variability, based on annual visits across three years. Higher diastolic BPV was significantly associated with reduced cortical thickness in multiple areas, including temporal (banks of the superior temporal sulcus), parietal (supramarginal gyrus, post-central gyrus), and posterior frontal areas (pre-central gyrus, caudal middle frontal gyrus), while controlling for mean BP. Higher diastolic BPV was associated with faster progression of cortical thinning across the three years. Diastolic BPV is an important predictor of cortical thickness, and trajectory of cortical thickness, independent of mean blood pressure. This finding suggests an important biological link in the relationship between BPV and cognitive decline in older age.

Metabolic syndrome and cognitive deficits in the Greek cohort of Epirus Health Study

BackgroundMetabolic syndrome is considered an important risk factor for cognitive decline and dementia. However, the evidence in middle-aged individuals is still conflicting. The aim of the study was to explore the association between metabolic syndrome and its individual components with cognitive function and to investigate possible interaction between sex, age and genetic predisposition for metabolic syndrome and Alzheimer’s disease in a middle-aged Greek cohort.MethodsA total of 2,077 healthy adults (mean age: 46.7 years) were included in the primary cross-sectional analysis and 305 of them in secondary prospective analyses. Metabolic syndrome was defined by the revised National Cholesterol Education-Adult Treatment Panel III and the International Diabetes Federation criteria. Cognitive function was measured primarily with the Trail Making, Verbal fluency and Logical Memory test, and in secondary prospective analyses with online versions of Posner cueing task, an emotional recognition task, Corsi block-tapping task and Stroop task.ResultsMultivariable linear regressions showed an association of metabolic syndrome with lower performance in attention (β=1.62 seconds, 95% CI=0.20, 3.04) and memory (β=-0.62 words, 95% CI=-1.19, -0.05) that could be driven by associations with elevated fasting glucose and abdominal obesity. Similar associations were observed in the secondary prospective analyses.ConclusionIn summary, metabolic syndrome was associated with cognitive deficits in domains related with the cognitive profile of vascular cognitive impairment.

PO-02-159 ABLATION OF ATRIAL FIBRILLATION AND DEMENTIA RISK REDUCTION DURING LONG-TERM FOLLOW-UP: A NATIONWIDE POPULATION-BASED STUDY

Growing evidence supports the hypothesis that AF is an independent risk factor for cognitive decline and dementia. Few studies have reported results regarding the subtypes of dementia in patients with AF in Asia. This study investigated the epidemiological characteristics of new-onset dementia in patients with AF and the effect of catheter ablation on different subtypes of dementia. We conducted a population-based, retrospective cohort study using data from the Taiwan National Health Insurance Research Database. In total, 136,774 patients without a history of dementia were selected after 1:1 propensity score matching based on age (with AF versus without AF). A competing risk model was used to investigate the three subtypes of dementia: Alzheimer's disease, vascular dementia, and other/mixed dementia. After a median follow-up period of 6.6 years, 8704 events of new-onset dementia occurred. Among all AF patients developing dementia, 73% were classified as having Alzheimer's disease, 16% as having vascular dementia, and 11% as having other/mixed dementia. The crude incidence of dementia in AF patients was higher (total dementia: 18.89 vs. 21.11, Alzheimer's disease: 15.13 vs. 16.81, vascular dementia: 2.08 vs. 3.77, and other/mixed dementia: 2.01 vs. 2.59 [per 1000 person-years, non-AF controls vs. AF patients]; all P < 0.001). In patients with AF undergoing catheter ablation, the total dementia risk decreased significantly (P = 0.015, hazard ratio: 0.74, 95% confidence interval: 0.58−0.94) after multivariable adjustment, but not for the subtype of vascular dementia (P = 0.59, hazard ratio: 0.86, 95% confidence interval: 0.49−1.50). Patients with AF have a higher incidence of all types of dementia, including Alzheimer's disease, vascular dementia, and a mixed type of dementia. Alzheimer's disease is less likely to occur in patients with AF undergoing catheter ablation.

(Zu-)Hören mit alterndem Gehirn – eine kognitive Herausforderung

Hearing impairment has been recently identified as a major modifiable risk factor for cognitive decline in later life and has been becoming of increasing scientific interest. Sensory and cognitive decline are connected by complex bottom-up and top-down processes, a sharp distinction between sensation, perception, and cognition is impossible. This review provides a comprehensive overview on the effects of healthy and pathological aging on auditory as well as cognitive functioning on speech perception and comprehension, as well as specific auditory deficits in the 2 most common neurodegenerative diseases in old age: Alzheimer disease and Parkinson syndrome. Hypotheses linking hearing loss to cognitive decline are discussed, and current knowledge on the effect of hearing rehabilitation on cognitive functioning is presented. This article provides an overview of the complex relationship between hearing and cognition in old age.

Remote Digital Technologies for the Early Detection and Monitoring of Cognitive Decline in Patients With Type 2 Diabetes: Insights From Studies of Neurodegenerative Diseases.

Type 2 diabetes (T2D) is a risk factor for cognitive decline. In neurodegenerative disease research, remote digital cognitive assessments and unobtrusive sensors are gaining traction for their potential to improve early detection and monitoring of cognitive impairment. Given the high prevalence of cognitive impairments in T2D, these digital tools are highly relevant. Further research incorporating remote digital biomarkers of cognition, behavior, and motor functioning may enable comprehensive characterizations of patients with T2D and may ultimately improve clinical care and equitable access to research participation. The aim of this commentary article is to review the feasibility, validity, and limitations of using remote digital cognitive tests and unobtrusive detection methods to identify and monitor cognitive decline in neurodegenerative conditions and apply these insights to patients with T2D.

Methylation status and sulfur amino-acids as risk factors for cognitive decline over 12 years: A longitudinal population based study (P4-6.002)

<h3>Objective:</h3> To investigate the association of vitamin B12, folate, and sulfur amino-acids with cognitive decline in a large sample of community dwelling older adults. <h3>Background:</h3> Impairment of methylation status and raised values of homocysteine and cysteine are common conditions in older adults and may be modifiable risk factors for cognitive decline. <h3>Design/Methods:</h3> From the Swedish National Study of Aging and Care in Kungsholmen (SNAC-K), 2900 dementia-free individuals at baseline aged 60–102 years with comprehensive assessments and Mini-mental state examination (MMSE) were recruited. A total of 2202 participants underwent repeated MMSE assessments up to 5 occasions over 12 years. The association of baseline vitamin B12, holotranscobalamin, folate, homocysteine, methionine, cystathionine, cysteine, glutathione, and methylation status (defined as serum methionine/homocysteine ratio) with rate of cognitive decline was examined using linear mixed models, adjusted for several potential confounders, including common vascular risk factors. <h3>Results:</h3> After adjusting for age, sex, education, creatinine, albumin, smoking status, systolic blood pressure, and <i>APOE</i>ɛ4 status, raised baseline serum total homocysteine and cysteine values were associated with a faster rate of cognitive decline: for the highest quartile compared with the lowest, β coefficient and standard error (SE) were −0.0058 (0.002) for homocysteine (p=0.004) and −0.0051 (0.002) for cysteine (p=0.014). In contrast, a better methylation status was associated with less MMSE decline over 15 years: β (SE) was 0.0058 (0.002) for the highest quartile compared with the lowest (p=0.004). Furthermore, elevated methionine values tended to slow rate of cognitive decline (p=0.079). No relationships were found for other sulfur amino acids, vitamin B12 or folate. <h3>Conclusions:</h3> Markers of methylation status and raised cysteine values were related to more rapid cognitive decline over 12 years, suggesting that optimizing homocysteine, cysteine, and methionine values may be important in reducing the risk of cognitive decline in older adults. <b>Disclosure:</b> Babak Hooshmand has nothing to disclose.

Ultrasound Imaging Markers of Carotid Atherosclerosis are Associated with Cognition Through Cerebral Small Vessel Disease on MRI (S15.001)

Ultrasound Imaging Markers of Carotid Atherosclerosis are Associated with Cognition Through Cerebral Small Vessel Disease on MRI (S15.001)

Analysis of cognitive function and its related factors after treatment in Meniere's disease.

A growing body of research recently suggested the association between vestibular dysfunction and cognitive impairment. Meniere's disease (MD), a common clinical vestibular disorder, is usually accompanied by hearing loss and emotional stress, both of which may mediate the relationship between vestibule dysfunction and cognition. It is currently unknown whether the cognitive decline in MD patients could improve through treatment and how it relates to multiple clinical characteristics, particularly the severity of vertigo. Therefore, in the present study, the MD patients were followed up for 3, 6, and 12 months after treatment, and the cognitive functions, vertigo symptoms, and related physical, functional, and emotional effects of the patients were assessed using the Montreal Cognitive Assessment (MoCA) and Dizziness Handicap Inventory (DHI), aiming to explore the change in cognition before and after therapy and the correlation with various clinical features. It was found that cognitive decline in MD patients compared to healthy controls before therapy. Importantly, this cognitive impairment could improve after effective therapy, which was related to the severity of vertigo, especially in functional and physical impacts. Our results support the view that vestibular dysfunction is a potentially modifiable risk factor for cognitive decline.

Risk Factors for Various Cognitive Function Decline Trajectories in Adults Over 40 Years of Age: A Retrospective Cohort Study.

The aims of our study were to identify distinct trajectories of cognitive function using the group-based trajectory model. We also investigate which demographic factors act as risk factors for cognitive decline in each group. The data from the Seoul National University Hospital Healthcare System Gangnam Center, from 2005 to 2019. The number of study subjects was 637. We used a group-based model to identify cognitive function trajectories. Multinomial logistic regression was employed to define risk factors for cognitive function decline. The cognitive function trajectories among adults over 40 years of age were heterogeneous. We identified four trajectories: high (27.3%), medium (41.0%), low (22.7%), and rapid decline (9.1%). Older age, male, low educational level, bad dietary habits, diabetes mellitus, technical worker, and lower income increased the likelihood of a cognitive function decline. A younger age, a higher educational level, professional worker, good dietary habits, no diabetes mellitus, and no obesity improved cognitive function. A combination of these factors can improve "cognitive reserve" and delay cognitive decline. Interventions to prevent cognitive decline are needed after identification of high-risk groups for cognitive decline.

Cognitive heterogeneity reveals molecular signatures of age-related impairment.

The greatest risk factor for cognitive decline is aging. The biological mechanisms for this decline remain enigmatic due, in part, to the confounding of normal aging mechanisms and those that contribute to cognitive impairment. Importantly, many individuals exhibit impaired cognition in age, while some retain functionality despite their age. Here, we establish a behavioral testing paradigm to characterize age-related cognitive heterogeneity in inbred aged C57BL/6 mice and reliably separate animals into cognitively "intact" (resilient) and "impaired" subgroups using a high-resolution home-cage testing paradigm for spatial discrimination. RNA sequencing and subsequent pathway analyses of cognitively stratified mice revealed molecular signatures unique to cognitively impaired animals, including transcriptional down-regulation of genes involved in mitochondrial oxidative phosphorylation (OXPHOS) and sirtuin (Sirt1 and Sirt3) expression in the hippocampus. Mitochondrial function assessed using high-resolution respirometry indicated a reduced OXPHOS coupling efficiency in cognitively impaired animals with subsequent hippocampal analyses revealing an increase in the oxidative damage marker (3-nitrotyrosine) and an up-regulation of antioxidant enzymes (Sod2, Sod1, Prdx6, etc.). Aged-impaired animals also showed increased levels of IL-6 and TNF-α gene expression in the hippocampus and increased serum levels of proinflammatory cytokines, including IL-6. These results provide critical insight into the diversity of brain aging in inbred animals and reveal the unique mechanisms that separate cognitive resilience from cognitive impairment. Our data indicate the importance of cognitive stratification of aging animals to delineate the mechanisms underlying cognitive impairment and test the efficacy of therapeutic interventions.

Exploring the secrets of super-aging: a UK Biobank study on brain health and cognitive function.

Communities across the globe are faced with a rapidly aging society, where age is the main risk factor for cognitive decline and development of Alzheimer's and related diseases. Despite extensive research, there have been no successful treatments yet. A rare group of individuals called "super-agers" have been noted to thrive with their exceptional ability to maintain a healthy brain and normal cognitive function even in old age. Studying their traits, lifestyles, and environments may provide valuable insight. This study used a data-driven approach to identify potential super-agers among 7121 UK Biobank participants and found that these individuals have the highest total brain volume, best cognitive performance, and lowest functional connectivity. The researchers suggest a novel hypothesis that these super-agers possess enhanced neural processing efficiency that increases with age and introduce a definition of the "neural efficiency index." Furthermore, several other types of aging were identified and significant structural-functional differences were observed between them, highlighting the benefit of research efforts in personalized medicine and precision nutrition.

Impact of Hearing Aids on Progression of Cognitive Decline, Depression, and Quality of Life Among People with Cognitive Impairment and Dementia.

Hearing loss is common in people with dementia (PwD) and a modifiable risk factor for cognitive decline. Recent studies revealed that hearing loss could cause social isolation and depression, which is associated with health-related quality of life (HRQoL). However, there is a lack of knowledge about the impact of the utilization of hearing aids on these outcomes. To assess whether hearing aids use might be positively associated with the progression of cognitive function, depression, and HRQoL among PwD. We analyzed two-year follow-up data from 258 PwD (≥70 years, living at home). Cognitive decline was measured with Mini-Mental Status Examination (MMSE), depression using Geriatric Depression Scale (GDS), and HRQoL with Quality of Life in Alzheimer's Disease Scale (QoL-AD). The impact of hearing aid utilization on the progression of outcomes was assessed using multivariate regression models. 123 patients had hearing loss (47.7%), from which n = 54 (43.9%) used hearing aids. Patients with hearing loss were older and had a lower HRQoL than those without hearing loss. Use of hearing aids in patients with hearing loss was associated with a lower increase in depressive symptoms (b = -0.74, CI95 -1.48 --0.01, p = 0.047) over time as compared to those not using hearing aids. There was no effect on PwD's cognition, and the association with higher HRQoL was significant after one, but not consistently over two years. Early detection and intervention of presbycusis using hearing aids might improve mental health and HRQoL in dementia.