Higher Risk Of Cognitive Decline Research Articles

The Utility of High Intensity Interval Training to Improve Cognitive Aging in Heart Disease Patients.

Adults with cardiovascular disease and heart failure are at higher risk of cognitive decline. Cerebral hypoperfusion appears to be a significant contributor, which can result from vascular dysfunction and impairment of cerebral blood flow regulation. In contrast, higher cardiorespiratory fitness shows protection against brain atrophy, reductions in cerebral blood flow, and cognitive decline. Given that high intensity interval training (HIIT) has been shown to be a potent stimulus for improving cardiorespiratory fitness and peripheral vascular function, its utility for improving cognitive aging is an important area of research. This article will review the physiology related to cerebral blood flow regulation and cognitive decline in adults with cardiovascular disease and heart failure, and how HIIT may provide a more optimal stimulus for improving cognitive aging in this population.

Social Support, social ties, and cognitive function of women with breast cancer: findings from the Women’s Health Initiative (WHI) Life and Longevity After Cancer (LILAC) Study

PurposeThis study examined associations between self-reported cognitive functioning and social support as well as social ties among women with breast cancer.MethodsThe study included 3351 women from the Women’s Health Initiative Life and Longevity After Cancer cohort who were diagnosed with breast cancer stages I–III. Social support was assessed using a modified Medical Outcomes Study (MOS) Social Support Survey, and marital status was obtained from the baseline questionnaire. We also assessed social ties (e.g., number of friends, relatives, living children) and cognitive function (Functional Assessment of Cancer Therapy-Cognitive Function [FACT-COG]) on the year-1-follow up questionnaire. Multivariable quantile regression was used to estimate the changes in median cognitive scores. Kruskal–Wallis tests were used to assess the association of cognitive function with social ties.ResultsThe majority of participants were non-Hispanic White (93.3%), presently married (49%), with at least a 4-year college degree (53.2%), and had been diagnosed with localized breast cancer (79%). A 10-point higher social support score correlated to a 0.32 higher (better) median cognitive score (p < 0.001). Women who were presently married tended to have better cognition than women who were divorced/separated or widowed (p = 0.01). Significant associations were also present for having close relatives (p < 0.001) or friends (p < 0.001), with cognitive scores being higher in those with at least one close relative or friend compared to none.ConclusionWomen reporting higher social support and greater numbers of friends or relatives have higher cognitive functioning. Compared to divorced or separated women, married women were likely to have higher cognitive functioning. These findings suggest that social support assessments have the potential to help identify women at higher risk of cognitive decline.

Correlation between Mild Cognitive Impairment and Sarcopenia: The Prospective Role of Lipids and Basal Metabolic Rate in the Link.

There is evidence of correlation between mild cognitive impairment (MCI) and sarcopenia (SA). However, the influencing factors and the mechanism, such as age-related lipid redistribution, remain unknown. This study aimed to clarify the role of dietary fats and erythrocyte lipids profile combined with basal metabolic rate (BMR) in the link between MCI and SA. A total of 1050 participants aged 65 to 85 were divided into control, MCI, SA and MCI and SA groups. Bioelectrical impedance analysis was used to evaluate appendicular lean mass and BMR. Cognition and dietary nutrition were detected by neuropsychological tests and food frequency questionnaires. UHPLC-QExactive-MS/MS and UHPLC-Qtrap-MS/MS were used to conduct the lipidomics analysis. Lower dietary intake of different phospholipids, unsaturated fatty acids and kinds of choline were significantly associated with MCI and SA. Least absolute shrinkage and selection operator, multivariate logistic regression, receiver operating characteristic curve and validation tests provided evidence that specific phospholipids, unsaturated fatty acids and BMR might be the critical factors in the processing of MCI and SA, as well as in their link. The lipidomic analysis observed a clear discrimination of the lipid profiles in the individuals who are in MCI, SA, or MCI and SA, compared with the control. Lower expressions in certain phospholipid species, such as sphingomyelin and phosphatidylethanolamines, decreased phosphatidylcholine with more unsaturated double bonds, lower level of lipids with C20:5 and C20:4, higher level of lipids with C18:2 and lipids with a remodeled length of acyl chain, might be closely related to the link between MCI and SA. Inadequate dietary intake and lower concentrations of the erythrocyte lipid profile of phospholipids and unsaturated fatty acids with a lower level of BMR might be the key points that lead to progress in MCI and SA, as well as in their link. They could be used as the prospective biomarkers for the higher risk of cognitive decline and/or SA in elderly population.

Changes in cognitive function after thoracoscopic and catheter ablation for atrial fibrillation.

Comparative data regarding the effect of percutaneous and thoracoscopic ablation of atrial fibrillation (AF) on cognitive function are very limited. The aim of the study was to determine and compare the effect of both types of ablations on patient cognitive functions in the mid-term. Patients with AF indicated for ablation procedure were included. Forty-six patients underwent thoracoscopic, off-pump ablation using the COBRA Fusion radiofrequency system, followed by a catheter ablation three months afterward (Hybrid group). A comparative cohort of 53 AF patients underwent pulmonary vein isolation only (PVI group). Neuropsychological examinations were done before and nine months after the surgical or catheter ablation procedure. Neuropsychological testing comprised 13 subtests of seven domains, and the results were expressed as post-operative cognitive dysfunction (POCD) nine months after the procedure. Patients in both groups were similar with respect to the baseline clinical characteristics; only non-paroxysmal AF was more common in the hybrid group (98%vs. 34%). Major POCD was present in eight (17.4%) of hybrid patients versus three (5.7%) of PVI patients (p=0.11), combined (major/minor) worsened cognitive decline was present in 10 (21.7%) hybrid patients versus three (5.6%) PVI patients (p=0.034). On the other hand, combined (major/minor) improvement was present in 15 (32.6%) hybrid patients versus nine (16.9%) patients in the PVI group (p=0.099). Hybrid ablation, a combination of thoracoscopic and percutaneous ablation, is associated with a higher risk of cognitive decline compared to sole percutaneous ablation.

Cognitive impairment and the threat of dementia pandemic or the journey of hypertensive patients to self-care deficit.

In the Czech Republic, due to the population aging, the prevalence of cognitive dysfunction is increasing. Researchers estimate that by 2050 the number of patients with dementia in the Czech Republic will more than double. Since dementia cannot be cured, it is important to prevent the cognitive dysfunction development by influencing modifiable risk factors. Arterial hypertension (AH) is one of the main risk factors for the development of cognitive dysfunction and dementia. Elevated blood pressure values in youth are associated with a higher risk of cognitive decline in middle age and with the development of dementia in old age. Blood pressure control in low-risk patients with stage I hypertension reduces the risk of dementia development, including Alzheimers disease. Therefore, improving the AH control in the population since younghood will be needed to influence the emerging cognitive dysfunction pandemic.

Concurrent hearing and vision impairment and 8-year memory decline in community-dwelling older adults.

Hearing and vision impairments are risk factors for cognitive decline; less is known about dual sensory impairment. This study quantifies the association between dual sensory impairment and 8-year change in memory among older adults. Data (N=5552) were from the National Health and Aging Trends Study. Memory (immediate/delayed word recall, subjective memory) was measured annually (2011 to 2019). Hearing and vision impairments were measured by self-report. Association between dual sensory impairment and 8-year change in memory was assessed using multivariate linear mixed effect models and generalized logistic mixed models. Rate of memory decline was most accelerated among participants with dual sensory impairment. For example, 8-year decline in delayed word recall was -1.03 (95% confidene interval: -1.29, -0.77) for dual sensory impairment versus -0.79 (-0.92, -0.67) for single and -0.56 (-0.63, -0.48) for no impairment. Older adults with dual sensory impairment may be at particularly higher risk for cognitive decline.

Utility of online cognitive test in cognitive neurology unit

AbstractBackgroundDelirium is one of the most common complications in hospitalized elders and corresponds with a higher risk of cognitive decline and death. Numerous test batteries exist to assist clinicians in detecting delirium, but it continues to be undiagnosed in up to 88% of patients, particularly those with AD where “confusion” is mistakenly attributed to impaired baseline (1). This pilot study investigated the utility of a digital cognitive assessment (D‐Cog), in the form of an iPad game, which would allow for rapid and routine baseline testing in patients with AD so that delirium‐induced changes can be easily detected.MethodWhile collecting traditional vital signs, medical assistants in the Beth Israel Deaconess Center (BIDMC) Cognitive Neurology Unit (CNU) prompted 67 willing patients to complete the D‐Cog assessment, an adaptive visuospatial span task, on an iPad. We then retrospectively reviewed the medical records of each patient to collect diagnosis, demographics, and pen‐and‐paper neuropsychological scores (e.g., MoCA or MMSE). Of the 67 patients (mean age 67, 29 female), 22 were clinically diagnosed with mild cognitive impairment (MCI) or varying severities of AD.ResultThe assessment was successfully completed by 52 participants. 15 participants, including 5 participants with moderate AD, experienced great difficulty during the task and were subsequently excluded. The 17 included participants with AD (mean age 75, 6 female) averaged a D‐Cog score of 4.1 and a MMSE score of 23.1. In comparison, a control group with no cognitive concerns (n = 16, mean age 60, 9 female) garnered a 6.7 average D‐Cog score and 29.3 MMSE score. The difference in D‐Cog scores was significantly different at p = 0.001.ConclusionThe D‐Cog assessment is feasible in clinical practice for patients with a wide range of cognitive impairments. These scores can act as an attentional baseline to compare against later testing in the event of suspected delirium. While the D‐Cog is derived from traditional pen‐and‐paper testing, its digital framework offers new opportunities for adaptive and remote testing.ReferenceFong TG, Davis D, Grodon ME, Albuquerque A, Inouye SK. The interface between delirium and dementia in elderly adults. Lancet Neruol. 2015; 14(8): 823–32

Do Sex Differences Exist in Cognitive Function in Patients with Atrial Fibrillation?

AbstractBackgroundAtrial fibrillation (AF) is a risk factor for mild cognitive impairment (MCI) and dementia. To address sex differences in AF‐related MCI, we examined disease prevalence and progression among adults with and without AF in the National Alzheimer’s Coordinating Center (NACC) cohort.MethodData freeze/extraction of NACC data (N = 43,746) took place March 2021. Participants with ≥ 3 annual visits, diagnostic data, and AF status (self‐reported or diagnosed) were included. Diagnostic categories were normal, MCI, and dementia. Multinomial logistic regression and Cox proportional hazard model were used to examine association between AF and baseline cognitive diagnosis and time to progression in cognitive diagnosis, respectively. Covariates included age, sex, race, education, BMI, smoking, depression, hypertension, diabetes, hypercholesterolemia, heart failure, stroke, and sleep apnea. Interactions with sex were examined in all models.Result4,593 participants had AF at baseline (46% female, mean age 78.5 years, 81% White, 8% Black, 11% other ethnicities). AF is associated with higher odds of having MCI (OR 3.43 [1.48, 7.91] in females; OR 1.73 [0.81, 3.71] in males) and dementia (OR 3.00 [1.22, 7.38] in females; OR 2.60 [1.16, 5.81] in males) at baseline. Among the 13,683 subjects included in the survival analysis, 4066 (30%) progressed from normal cognition to MCI and 2895 (21%) developed dementia (2434 [18%] AD) with median follow‐up of 4 years. Women with AF had higher risk of disease progression (HR 1.21 [1.04, 1.40]) compared to women without AF, but the association was not significant in men (HR 0.96 [0.83, 1.11]). AF was significantly associated with faster transition from normal cognition to MCI (HR 1.17 [1.03, 1.33]) and from MCI to vascular dementia (HR 2.51 [1.63, 3.85]) but not MCI to AD.ConclusionThis is the first study to examine sex differences in rate of cognitive change in patients with AF. Women with AF are at higher risk of MCI and dementia with more rapid trajectories to dementia than women without AF or men with or without AF. Identification of those at highest risk of cognitive decline will inform future interventions to prevent or slow AF‐related MCI and AD.

Trial Enrichment using Siamese Neural Networks and PET imaging

AbstractBackgroundBiomarker‐based patient selection is expected to increase success rates in AD clinical trials (e.g. identifying subjects that are at highest risk of cognitive decline). We present a computationally feasible modelling framework that provides a score for predicted decline based on a model trained through a Siamese Neural Network.MethodIn this proof‐of‐concept study, we use baseline data from the 1469 ADNI subjects (388 control, 798 MCI, 272 AD) with an FDG PET scan. 80% of the data was used to train a Siamese neural network after clustering subjects into ‘stable’ or ‘decline’ through the method of Bhagwat et al (2018), see Figure 1. 20% of the data was left out for testing.The model outputs points in a metric space, indicating likelihood of future decline (measured using 2‐year MMSE change from baseline). The first PCA component of the model metric space is used as a screening criterion (See Fig 2). Subjects below the threshold (screen failure rates of 30% and 50%) are not included in the trial simulation. Sample sizes are estimated assuming a 25% effect size, 95% alpha and 80% power (Fig 3). Enrichment performance of the model is compared with FDG SUVR and baseline MMSE score.ResultThe neural network provides a separable metric space of future declining and stable subjects. ‘Screening’ out 30% and 50% of subjects based on model‐predicted decline resulted in a sample size reduction of 45% and 64% respectively, a 5% and 10% improvement over the enriched FDG SUVR cohort. MMSE score yields marginal enrichment. Saliency analysis showed the model is sensitive to the precuneus, hippocampus, temporal lobe and cerebellum.ConclusionDeep learning models enable automated trial enrichment strategies, instead of handcrafted features and centralised processing. The saliency analysis shows that the nonlinear framework has identified the relevant regions for the pathology, providing additional support to their use. More work is needed to assess the ability of the developed method to capture multi‐modal biomarker (e.g. Amyloid, Tau, Neurodegeneration) data to obtain a more precise prediction of decline and to assess the trial operational and economic impact of the proposed screening process.

COVID-19 Takes Cognitive Toll on Older Patients

COVID-19 Takes Cognitive Toll on Older Patients

The role of spirituality and religiosity on the cognitive decline of community-dwelling older adults: a 4-year longitudinal study

Objectives This study aims to assess whether having religious beliefs, attending religious services and using spiritual-religious coping (SRC) are longitudinally associated with cognitive decline in community-dwelling older adults. Methods A 4-year longitudinal study of 261 Brazilian older adults was conducted. Hierarchical adjusted linear regression models and logistic regression models were performed to evaluate the longitudinal effects of religious beliefs, church attendance and positive and negative SRC on cognitive decline. Results The findings revealed that spiritual and religious beliefs at baseline could affect cognitive function in two different ways. When older adults use religiosity and spirituality (RS) in a functional positive manner, it results in better cognitive outcomes and a slower rate of decline. However, when used in a negative manner, it results in worse cognitive outcomes. Conclusion These results could help health care professionals address SRC among older adults, particularly those at a higher risk of cognitive decline. Considering that RS is very important for older adults, health care professionals should be aware of the beliefs of their patients and address RS in clinical practice.

Adherence to High Dietary Diversity and Incident Cognitive Impairment for the Oldest-Old: A Community-Based, Nationwide Cohort Study

Dietary diversity change is associated with cognitive function, however, whether the effect still exists among the oldest-old (80+) is unclear. Our aim was to examine the effect of dietary diversity changes on cognitive impairment for the oldest-old in a large prospective cohort. Within the Chinese Longitudinal Healthy Longevity Study, 6237 adults older than 80 years were included. The dietary diversity score (DDS) was assessed by a simplified food frequency questionnaire (FFQ). Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score lower than 18 points. Cognitive decline was defined as a reduction of total MMSE score ≥3 points, and cognitive decline of different subdomains was defined as a reduction of ≥15% in the corresponding cognitive domain. The multivariate-adjusted Cox proportional hazard model evaluated the effects of DDS change on cognitive decline. The linear mixed-effect model was used to test subsequent changes in MMSE over the years. During 32,813 person-years of follow-up, 1829 participants developed cognitive impairment. Relative to the high-high DDS change pattern, participants in the low-low and high-low patterns were associated with an increased risk of cognitive impairment with a hazard ratio (95% confidential interval, CI) of 1.43 (1.25, 1.63) and 1.44 (1.24, 1.67), and a faster decline in the MMSE score over the follow-up year. Participants with the low-high pattern had a similar incidence of cognitive impairment with HRs (95% CI) of 1.03 (0.88, 1.20). Compared with the stable DDS status group (-1-1), the risk of cognitive impairment was higher for those with large declines in DDS (≤-5) and the HR was 1.70 (95% CI: 1.44, 2.01). Even for people older than 80, dietary diversity change is a simple method to identify those who had a high risk of cognitive decline. Keeping high dietary diversity is beneficial for cognitive function and its subdomain even in the final phase of life, especially for females and the illiterate oldest-old.

The Impact of Anticholinergic Use for Overactive Bladder on Cognitive Changes in Adults with Normal Cognition, Mild Cognitive Impairment, or Dementia

BackgroundFew studies have addressed whether anticholinergic (AC) medications for overactive bladder (OAB) cause cognitive decline in individuals with existing cognitive impairment, and whether the APOE ε4 gene increases this risk. ObjectiveTo determine whether OAB AC use is associated with a clinically relevant change in cognitive measures among adults with normal and abnormal cognition. Design, setting, and participantsThis was a retrospective cohort study using data from the National Alzheimer’s Coordinating Center. Patients were enrolled at specialized centers in the USA between 2005 and 2019. Patients with existing OAB AC use, missing APOE ε4 status, and confounding neurologic diagnoses were excluded. New users of an OAB AC were matched 1:1 to patients not taking an OAB AC using propensity scores. InterventionNew use of oxybutynin, tolterodine, solifenacin, trospium, darifenacin, or fesoterodine. Outcome measurements and statistical analysisThe outcome was a change in cognitive function, measured as a ≥1-point increase on the Clinical Dementia Rating (CDR) instrument or a ≥3-point decrease on the Mini-Mental State Examination (MMSE). Conditional logistic regression with odds ratios (ORs) was conducted. We also tested for APOE ε4 effect modification. Results and limitationsAmong 18 835 eligible patients, 782 matched pairs were identified. The most common OAB ACs were oxybutynin (38%) and tolterodine (23%). There was no significant increase in the risk of a clinically relevant cognitive decline among OAB AC users (CDR: OR 1.38, 95% confidence interval [CI] 0.93–2.05; p = 0.11, MMSE: OR 1.06, 95% CI 0.79–1.43; p = 0.70). There was no significant interaction between APOE ε4 status and OAB AC use for the CDR (p = 0.38) or MMSE (p = 0.95) outcomes. Users of oxybutynin or tolterodine had numerically higher odds of a change on the CDR test (OR 1.65, 95% CI 0.98–2.77) that was close to statistical significance (p = 0.06). Limitations include the inability to determine medication dose or duration, and residual confounding. ConclusionsOAB AC use was not associated with a significant change in cognitive function among individuals with normal and abnormal cognition. Further research is necessary to determine if oxybutynin and tolterodine are significantly more likely to cause cognitive decline. Patient summaryUse of a specific class of overactive bladder medication was not associated with negative changes in brain function among patients with either normal or abnormal function. A genetic risk factor for Alzheimer’s disease did not predispose individuals to cognitive decline when taking these drugs. Two of the drugs (oxybutynin and tolterodine) may lead to a higher risk of cognitive decline in comparison to other drugs, and this needs further research.

Pre-frail older adults show improved cognition with StayFitLonger computerized home–based training: a randomized controlled trial

Multidomain interventions have shown tremendous potential for improving cognition in older adults. It is unclear if multidomain interventions can be delivered remotely and whether remote intervention is beneficial for older adults who are vulnerable or at risk of cognitive decline. In a 26-week multi-site, home-based, double-blind, randomized controlled trial, 120 cognitively healthy older adults (75 robust, 45 pre-frail; age range = 60–94) recruited from Switzerland, Canada, and Belgium were randomized to receive either the StayFitLonger (SFL) computerized multidomain training program or an active control intervention. Delivered on tablets, the SFL intervention combined adapted physical exercises (strength, balance, and mobility), cognitive training (divided attention, problem solving, and memory), opportunities for social and contributive interactions, and psychoeducation. The active control intervention provided basic mobilization exercises and access to video games. Cognitive outcomes were global cognition (Z-scores of attention, verbal fluency, and episodic memory for nondemented older adults; ZAVEN), memory, executive function, and processing speed. Linear mixed model analyses indicated improved performance on the ZAVEN global cognition score in the SFL group but not in the active control group. Stratified analyses by frailty status revealed improved ZAVEN global cognition and processing speed scores following SFL in the pre-frail group but not in the robust group. Overall, the study indicates that a computerized program providing a multidomain intervention at home can improve cognition in older adults. Importantly, pre-frail individuals, who are at higher risk of cognitive decline, seem to benefit more from the intervention. Trial registration: ClinicalTrials.gov, NCT037519 Registered on January 22, 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04237519.

Aberrant brain functional networks in type 2 diabetes mellitus: A graph theoretical and support-vector machine approach.

ObjectiveType 2 diabetes mellitus (T2DM) is a high risk of cognitive decline and dementia, but the underlying mechanisms are not yet clearly understood. This study aimed to explore the functional connectivity (FC) and topological properties among whole brain networks and correlations with impaired cognition and distinguish T2DM from healthy controls (HC) to identify potential biomarkers for cognition abnormalities.MethodsA total of 80 T2DM and 55 well-matched HC were recruited in this study. Subjects’ clinical data, neuropsychological tests and resting-state functional magnetic resonance imaging data were acquired. Whole-brain network FC were mapped, the topological characteristics were analyzed using a graph-theoretic approach, the FC and topological characteristics of the network were compared between T2DM and HC using a general linear model, and correlations between networks and clinical and cognitive characteristics were identified. The support vector machine (SVM) model was used to identify differences between T2DM and HC.ResultsIn patients with T2DM, FC was higher in two core regions [precuneus/posterior cingulated cortex (PCC)_1 and later prefrontal cortex_1] in the default mode network and lower in bilateral superior parietal lobes (within dorsal attention network), and decreased between the right medial frontal cortex and left auditory cortex. The FC of the right frontal medial-left auditory cortex was positively correlated with the Montreal Cognitive Assessment scales and negatively correlated with the blood glucose levels. Long-range connectivity between bilateral auditory cortex was missing in the T2DM. The nodal degree centrality and efficiency of PCC were higher in T2DM than in HC (P < 0.005). The nodal degree centrality in the PCC in the SVM model was 97.56% accurate in distinguishing T2DM patients from HC, demonstrating the reliability of the prediction model.ConclusionFunctional abnormalities in the auditory cortex in T2DM may be related to cognitive impairment, such as memory and attention, and nodal degree centrality in the PCC might serve as a potential neuroimaging biomarker to predict and identify T2DM.

Physical activity trajectories and cognitive function: A national cohort study

ObjectiveTo examine the prospective associations between physical activity trajectories, measured from repeated assessments over time, and cognitive function. MethodA total of 2972 participants aged 45 years old and over (median age: 56.0 [interquartile range - IQR 50.0–62.0], 50.8% males]) from the Chinese Health and Retirement Longitudinal Study (CHARLS) study were included. First, our study used the growth mixture modeling to identify physical activity trajectories from the first three surveys of the CHARLS. Second, we performed regression analysis to explore the associations of the trajectories with 3-year cognitive function. ResultsWe identified four physical activity trajectories, characterized by persistently low (N = 1880), initially low then increasing (154), initially moderate then decreasing (584), and initially high then decreasing (354). After 3-year follow-up, compared to individuals with persistently low trajectory, those with initially moderate then decreasing (β = −0.74, 95% CI = (−1.38, −1.10), p = 0.024) and initially high then decreasing (β = −1.12, 95% CI = (−1.91, −0.33), p = 0.005) were significantly associated with cognitive decline. The effects of the decline in physical activity on cognitive function varied by sex. Females’ cognitive function (β = −1.79, 95% CI = (−2.82, −0.77) was more likely to be influenced by decreasing physical activity, but this association was not significant in males. We did not find the significant effect of initially low then increasing trajectory on cognitive function. ConclusionsFast decline in physical activity is related to a higher risk of cognitive decline, especially in females.

Quantifying the post-radiation accelerated brain aging rate in glioma patients with deep learning.

Changes of healthy appearing brain tissue after radiotherapy (RT) have been previously observed. Patients undergoing RT may have a higher risk of cognitive decline, leading to a reduced quality of life. The experienced tissue atrophy is similar to the effects of normal aging in healthy individuals. We propose a new way to quantify tissue changes after cranial RT as accelerated brain aging using the BrainAGE framework. BrainAGE was applied to longitudinal MRI scans of 32 glioma patients. Utilizing a pre-trained deep learning model, brain age is estimated for all patients' pre-radiotherapy planning and follow-up MRI scans to acquire a quantification of the changes occurring in the brain over time. Saliency maps were extracted from the model to spatially identify which areas of the brain the deep learning model weighs highest for predicting age. The predicted ages from the deep learning model were used in a linear mixed effects model to quantify aging of patients after RT. The linear mixed effects model resulted in an accelerated aging rate of 2.78years/year, a significant increase over a normal aging rate of 1 (p<0.05, confidence interval=2.54-3.02). Furthermore, the saliency maps showed numerous anatomically well-defined areas, e.g.: Heschl's gyrus among others, determined by the model as important for brain age prediction. We found that patients undergoing RT are affected by significant post-radiation accelerated aging, with several anatomically well-defined areas contributing to this aging. The estimated brain age could provide a method for quantifying quality of life post-radiotherapy.

The Role of Physical Activity on the Relationships Between Pain, Anxiety, and Sleep Quality in Older Age.

Sleep quality is associated with a range of negative outcomes in older adults, including a higher risk for cognitive decline, greater disability, and poorer quality of life. Pain and anxiety are both important factors associated with poor sleep quality. Physical activity (PA) is frequently recommended to enhance sleep quality and may have additional benefits for pain and anxiety symptoms. However, current models have not examined the interplay among these factors in relation to sleep quality in older adults. We examined survey data from a community sample of 281 older adults (aged 55-98years). Bootstrapped mediation and moderated mediation models using the PROCESS macro in SPSS were used to analyze indirect pathways from pain and anxiety to sleep quality and the conditional effects of exercise. Higher levels of pain and anxiety were significantly and independently associated with poorer sleep quality in older adults. The effect of pain on sleep quality was partially mediated by anxiety symptoms. PA significantly moderated the effects of anxiety on sleep quality, while it did not significantly impact the relationship between pain and sleep quality. The overall indirect effect was not moderated byPA. Pain and anxiety are both significant predictors of sleep quality in older adults, and pain influences sleep quality in older adults partially through its influence on anxiety symptoms. PA may be beneficial for sleep quality for individuals with high anxiety, but patients may see fewer benefits from PA if sleep problems are primarily related to pain.

Distressing dreams, cognitive decline, and risk of dementia: A prospective study of three population-based cohorts.

SummaryBackgroundDistressing dreams are associated with faster cognitive decline and increased dementia risk in people with Parkinson's disease (PD). Whether distressing dreams might be associated with cognitive decline and dementia in people without PD is unknown. This study investigated the association between self-reported distressing dream frequency and the risk of cognitive decline and incident dementia in community-dwelling men and women without cognitive impairment or PD.MethodsRisk of cognitive decline was evaluated in 605 middle-aged adults (mean age = 50 years [IQR 44–57]; 55·7% female) from the Midlife in the United States (MIDUS) study, who were cognitively normal at baseline, and were followed-up for a maximum of 13 years (IQR 9–10). Cognitive decline was defined as having an annual rate of decline in global cognitive function (measured using five cognitive tests) ≥ 1 standard deviation faster than the mean decline rate from baseline to follow-up. Risk of incident all-cause dementia was evaluated in 2600 older adults (mean age = 83 years [IQR 81–84]; 56·7% female) pooled from the Osteoporotic Fractures in Men Study (MrOS) and the Study of Osteoporotic Fractures (SOF), who were dementia-free at baseline, and were followed-up for up a maximum of 7 years (IQR 4–5). Incident dementia was based on doctor-diagnosis. Frequency of distressing dreams was assessed in all cohorts at baseline (January 2002 – March 2012) using item 5h of the Pittsburgh Sleep Quality Index. The association between self-reported distressing dream frequency (“never”, “less than weekly”, “weekly”) and later cognitive outcomes, was evaluated using multivariable logistic regression in both the middle-aged and pooled older adult cohorts.FindingsAfter adjustment for all covariates, a higher frequency of distressing dreams was linearly and statistically significantly associated with higher risk of cognitive decline amongst middle-aged adults (P for trend = 0·016), and higher risk of incident all-cause dementia amongst older adults (P for trend <0·001). Compared with middle-aged adults who reported having no distressing dreams at baseline, those who reported having weekly distressing dreams had a 4-fold risk of experiencing cognitive decline (adjusted odds ratio [aOR] = 3·99; 95% CI: 1·07, 14·85). Amongst older adults, the difference in dementia risk was 2·2-fold (aOR = 2·21; 95% CI: 1·35, 3·62). In sex-stratified analyses, the associations between distressing dreams and both cognitive outcomes were only statistically significant amongst men.InterpretationDistressing dreams predict cognitive decline and all-cause dementia in middle-aged and older adults without cognitive impairment or PD - especially amongst men. These findings may help to identify individuals at risk of dementia and could facilitate early prevention strategies.FundingThe study received no external funding.

Patterns and risk factors of cognitive decline among community-dwelling older adults in South Korea

Dementia prevalence is increasing worldwide. Thus, the global impact of cognitive impairment and dementia have become significant public health issues. This study assessed the patterns of and investigated risk factors associated with cognitive decline over time in community-dwelling Korean adults (age ≥65 years). We enrolled 1,369 older adult respondents without cognitive decline in the baseline survey of the Korean Longitudinal Study of Aging (2006–2016) in South Korea. The risk of first-ever mild-to-moderate or severe cognitive decline during the 10-year follow-up (2006–2016) was comparatively evaluated between the cognitive decline group (comprising participants with mild-to-moderate or severe cognitive decline; n = 728) and the normal cognition group (participants without a cognitive decline event; n = 641). The cognitive decline-free survival rates for up to ten years were measured using Kaplan–Meier analysis. The generalized estimation equations model was used to analyze changes in K-MMSE over time from 2006 to 2016. The adjusted Cox proportional hazards model revealed that increased age, female, lower education level, no religious status, and living in a small city were factors that were associated with a higher risk of cognitive decline, as were health-related factors, including lower handgrip strength, a higher number of chronic diseases, and depressive symptoms. Regular exercise, non-drinking status, and active social engagements reduced the risk of cognitive decline. The identified risk factors could facilitate the development of cognitive decline-prevention programs incorporating individualized risk-modification interventions to prevent cognitive decline in older adults.