Risk Factor For Cognitive Decline Research Articles

Loneliness and cognitive function in older adults: Longitudinal analysis in 15 countries.

This study aims to evaluate the directionality of the association between loneliness and cognitive performance in older adults, accounting for confounding factors. Data were from 55,662 adults aged ≥ 50 years who participated in Waves 5-8 of the Survey of Health, Ageing and Retirement in Europe (SHARE). Loneliness was assessed with the Three-Item Loneliness Scale (TILS) and with a one-item direct question. Cognitive performance was assessed with four measures: verbal fluency, numeracy, immediate recall, and delayed recall. Age, sex, geographical area, educational attainment, partnership status, depressive symptoms, and previous chronic diseases at baseline were used as covariates. We analyzed the associations with three-wave random intercept cross-lagged panel models (RI-CLPM) and conducted age-stratified analysis among those younger versus older than 65 years. Full information maximum likelihood estimators were used to handle missing values in Waves 6-8 in the main analyses. We also conducted additional sensitivity analyses stratified by retirement status (retired vs. not) at baseline. At the within-person level, loneliness and cognitive performance were not associated with each other among those aged 50-64 years in the main time-lagged analysis. Among those aged ≥ 65 years, loneliness was associated with lower cognitive performance in the next wave in all four cognitive domains. In addition, lower verbal fluency predicted greater loneliness in the next waves among this age group. Similar patterns were found independently of retirement status at baseline. These results suggest that loneliness is a psychosocial risk factor for cognitive decline among older adults (≥ 65 years). (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Causal inference on strategies to increase conversational engagement for socially isolated older adults

AbstractBackgroundSocial isolation, characterized by a small social network and lack of contact, negatively impact the quality of life. Older adults are at an increased risk for social isolation, which is found to be a risk factor of cognitive decline and dementia. Enhancing social connectedness or interactions has been shown to be an effective intervention for slowing age‐associated cognitive decline and possibly delaying the onset of dementia. Here we aim to develop conversational chatbots which can provide engaging conversations with older adults with mild cognitive impairment (OAwMCI) to mitigate social isolation. To resemble human human interactions, chatbots have to adapt certain human strategies, such as empathy, during conversation.MethodOur study utilized causal structural learning and causal inference approaches to examine the dialogue strategy for engaging OAwMCI. We analyzed transcriptions from a clinical trial, I‐CONECT (ClinicalTrials.gov #: NCT02871921), which involved semi‐structured conversations between facilitators and participants. By using emotion recognition in conversation and dialogue act modeling, we produced a time series data of state (participant’s emotions and length of utterance per conversation turn), intervention (facilitator’s conversational strategies), and outcome (participant’s following emotions and engagement). A R package, pcalg, was used to identify causal relationships between the state, intervention, and outcome variables.ResultGraphical models implying causal relationships between certain factors were generated. Our analysis revealed that facilitators adjusted their dialogue strategies according to the participants' emotions and utterance. For example, facilitators expressed appreciation when a participant showed . Additionally, we found that the dialogue acts from facilitators influenced participants' emotions and engagement in the conversation. For instance, non‐opinion statements and yes/no questions from facilitators may affect participants’ verbal engagement and level of anger during the conversation.ConclusionFindings from this study are in line with real‐world human‐human conversation, and our next step is to explore how to use these findings to improve conversational chatbots. Future work shall also consider other crucial features into the state variable that might influence the dynamics of participants' status during the conversation, such as cognitive capacity and dialogue coherence. Our findings have the potential to inform the development of conversational tools and strategies to reduce social isolation among OAwMCI.

Are changes in muscular strength following head‐down bed rest independently associated with improved cognitive function in older adults? A secondary analysis of a randomized controlled trial

AbstractBackgroundPhysical inactivity is common among older adults and is a risk factor for cognitive decline. Even a brief period of physical inactivity, such as bed rest due to hospitalization, in older adults has significant negative impacts. Exercise is strategy to counter the negative effects of physical inactivity. Exercise‐induced improvements in cardiorespiratory fitness is associated with improved cognitive function. Less is known regarding the contribution of exercise‐induced changes in muscle strength to changes in cognitive function. Thus, we aimed to examine the independent contribution of: 1) change in cardiorespiratory fitness; and 2) change in peak muscle torque of the lower extremity to changes in cognitive function in a randomized controlled trial (RCT) of head‐down bed rest (HDBR) vs. HDBR with exercise in healthy older adults.MethodAn analysis of a non‐blinded, parallel‐group, RCT of 22 healthy older adults (11 males and 11 females) aged 55‐65 years. Participants were randomized to: 1) 14 days of 6° HDBR (CON); or 2) HDBR with daily resistance and aerobic exercise training (EX). Outcome measures were taken at baseline and HDBR completion. The Flanker Inhibitory Control and Attention Task measured executive function. Physical fitness measures included: 1) maximal aerobic capacity (VO2max) using a bicycle ergometry test; and 2) knee extension isokinetic muscular strength (KE) using a Biodex dynamometer. We performed two separate multiple linear regressions to determine whether following 14 days of HDBR: 1) VO2max was associated with Flanker score, after accounting for ΔKE; and 2) KE was associated with Flanker score, after accounting for ΔVO2max. Each model was also adjusted for baseline Flanker score and the baseline physical fitness measure of interest.ResultAt baseline, average Flanker t‐score was 48.33, mean VO2max was 32.527 ml/kg/min, and knee extension strength was 64.472 Nm. VO2max at follow‐up was not significantly associated with Flanker performance (b = 0.232 ± 0.716; p = 0.635; R2 adj. = 0.285). However, greater KE strength was significantly associated with better Flanker performance (b = 2.023 ± 0.389; p = 0.043; R2 adj. = 0.633) at HDBR completion.ConclusionThe maintenance of muscle strength even during brief periods of physical inactivity appears to be critical for cognitive health in older adults.

Late‐life hypertension acts together with amyloid‐β pathology to promote early cognitive decline

AbstractBackgroundMidlife hypertension (HTN) is a known risk factor for Alzheimer’s Disease (AD) development. However, whether the same effect is observed in older individuals, at risk for AD, remains to be elucidated. Here, we aimed to assess whether late‐life HTN and the presence of amyloid‐β pathology (Aβ) interact to promote longitudinal cognitive decline in cognitively unimpaired (CU) individuals, and if systolic blood pressure (SBP) levels moderate this interaction. Interactive effect of disease pathophysiology is crucial for dementia prevention strategies.MethodWe used two independent cohorts. We evaluated 475 CU individuals over 65 years of age from the ADNI cohort, with available baseline medical data and CSF Elecsys biomarkers (Aβ1‐42 and p‐tau181), as well as longitudinal clinical assessments with neuropsychological testing (up to 6 years); the individuals were classified as (A)+ or (A)‐ based on a previously proposed cut‐off of CSF p‐tau181/Aβ1‐42 lower than 0.025. We also evaluated 162 CU individuals over 65 years of age from the TRIAD cohort with baseline clinical data and Aβ‐PET, as well as longitudinal clinical assessments with neuropsychological testing (up to 3 years). The individuals were classified as (A)+ or (A)‐ based on Aβ‐PET positivity. All individuals were classified as positive or negative for hypertension based on medical history. For the ADNI cohort, we could also evaluate the SBP levels as a continuous variable.ResultLinear mixed‐effects (LME) models showed that HTN and Aβ acted together to promote longitudinal cognitive decline (ADNI: HTN X Aβ X Time, β = ‐0.44, p = 0.001, figure 1, TRIAD: HTN X Aβ X Time, β = ‐0.64, p < 0.001, figure 2). Also, we could see that higher SBP levels acted together with Aβ to promote further cognitive decline (SBP values X Aβ X Time, β = ‐0.011, p = 0.03, figure 3).ConclusionOur results support a framework in which late‐life HTN is a modifiable risk factor for cognitive decline in CU individuals at increased risk for AD. This supports further investigation in determining the best target of SBP levels for individuals at risk for AD, in the context of offering precision medicine for this population.

Socioeconomic position, modifiable dementia risk and cognitive decline: results of 12‐year Maastricht Aging Study

AbstractBackgroundEvidence of modifiable risk factors for cognitive decline and dementia is accumulating, showing the potential of dementia risk reduction via lifestyle modification and cardiovascular risk management. People with low socioeconomic status (SES) have increased dementia risk and on average worse health. This study investigated whether the association between a modifiable dementia risk score and rate of cognitive decline differs across SES strata.MethodData were used from Maastricht Aging Study (MAAS), a prospective cohort study with a 12‐year follow‐up. Participants aged ≥40 years with complete dementia risk profiles were included (n = 1223). The validated ’LIfestyle for BRAin health’ (LIBRA) index was used to assess the modifiable dementia risk fraction. Cognitive performance was serially assessed at baseline, 6 and 12 years and measured in the domains of information processing speed, executive functioning and verbal memory function. A SES compound score was calculated from equivalent income and educational level and divided into tertiles (low, middle, high). Linear mixed models were used to study the association between LIBRA, SES and their interaction on the rate of cognitive decline.ResultParticipants in the lowest SES tertile displayed more decline in information processing speed (vs. middle SES: X2 = 7.08, p = 0.029; vs. high SES: X2 = 9.49, p = 0.009) and verbal memory (vs. middle SES: X2 = 9.28, p<0.001; vs. high SES: X2 = 16.68, p<0.001) compared to their middle‐ and high‐SES counterparts. Higher (unhealthier) LIBRA scores were also associated with more decline in information processing speed (X2 = 12.66, p = 0.002) and verbal memory (X2 = 4.63, p = 0.032). No consistent effect modification by SES on the association between LIBRA and cognition was found.ConclusionThis study shows that lower SES and higher modifiable dementia risk predict faster decline in information processing speed and verbal memory function over 12 years. Results suggest that lifestyle is an important determinant of cognitive decline across SES groups. Yet, people with low SES had a more unfavourable modifiable risk score suggesting more potential for lifestyle‐based interventions. LIBRA could be useful as a participant selection tool or as a surrogate outcome measure in lifestyle intervention trials, and can inform people about individual risk behaviours as part of public health initiatives.

5 LIfestyle for BRAin Health (LIBRA) Modifiable Factors Risk Score and Concussion History Associations with Cognition in Older Former National Football League Players.

Objective:Traumatic brain injury is one of several recognized risk factors for cognitive decline and neurodegenerative disease. Currently, risk scores involving modifiable risk/protective factors for dementia have not incorporated head injury history as part of their overall weighted risk calculation. We investigated the association between the LIfestyle for BRAin Health (LIBRA) risk score with odds of mild cognitive impairment (MCI) diagnosis and cognitive function in older former National Football League (NFL) players, both with and without the influence of concussion history.Participants and Methods:Former NFL players, ages ≥ 50 (N=1050; mean age=61.1±5.4-years), completed a general health survey including self-reported medical history and ratings of function across several domains. LIBRA factors (weighted value) included cardiovascular disease (+1.0), hypertension (+1.6), hyperlipidemia (+1.4), diabetes (+1.3), kidney disease (+1.1), cigarette use history (+1.5), obesity (+1.6), depression (+2.1), social/cognitive activity (-3.2), physical inactivity (+1.1), low/moderate alcohol use (-1.0), healthy diet (-1.7). Within Group 1 (n=761), logistic regression models assessed the association of LIBRA scores and independent contribution of concussion history with the odds of MCI diagnosis. A modified-LIBRA score incorporated concussion history at the level planned contrasts showed significant associations across concussion history groups (0, 1-2, 3-5, 6-9, 10+). The weighted value for concussion history (+1.9) within the modified-LIBRA score was based on its proportional contribution to dementia relative to other LIBRA risk factors, as proposed by the 2020 Lancet Commission Report on Dementia Prevention. Associations of the modified-LIBRA score with odds of MCI and cognitive function were assessed via logistic and linear regression, respectively, in a subset of the sample (Group 2; n=289) who also completed the Brief Test of Adult Cognition by Telephone (BTACT). Race was included as a covariate in all models.Results:The median LIBRA score in the Group 1 was 1.6(IQR= -1, 3.6). Standard and modified-LIBRA median scores were 1.1(IQR= -1.3, 3.3) and 2(IQR= -0.4, 4.6), respectively, within Group 2. In Group 1, LIBRA score was significantly associated with odds of MCI diagnosis (odds ratio[95% confidence interval]=1.27[1.19, 1.28], p <.001). Concussion history provided additional information beyond LIBRA scores and was independently associated with odds of MCI; specifically, odds of MCI were higher among those with 6-9 (Odds Ratio[95% confidence interval]; OR=2.54[1.21, 5.32], p<.001), and 10+ (OR=4.55;[2.21, 9.36], p<.001) concussions, compared with those with no prior concussions. Within Group 2, the modified-LIBRA score was associated with higher odds of MCI (OR=1.61[1.15, 2.25]), and incrementally improved model information (0.04 increase in Nagelkerke R2) above standard LIBRA scores in the same model. Modified-LIBRA scores were inversely associated with BTACT Executive Function (B=-0.53[0.08], p=.002) and Episodic Memory scores (B=-0.53[0.08], p=.002).Conclusions:Numerous modifiable risk/protective factors for dementia are reported in former professional football players, but incorporating concussion history may aid the multifactorial appraisal of cognitive decline risk and identification of areas for prevention and intervention. Integration of multi-modal biomarkers will advance this person-centered, holistic approach toward dementia reduction, detection, and intervention.

6 Improved verbal fluency following unilateral right hemisphere subthalamic nucleus deep brain stimulation for Parkinson’s disease: Is implant hemisphere a modifiable risk factor for cognitive decline?

Objective:Non-motor symptoms, such as mild cognitive impairment and dementia, are an overwhelming cause of disability in Parkinson’s disease (PD). While subthalamic nucleus deep brain stimulation (STN DBS) is safe and effective for motor symptoms, declines in verbal fluency after bilateral DBS surgery have been widely replicated. However, little is known about cognitive outcomes following unilateral surgeries.Participants and Methods:We enrolled 31 PD patients who underwent unilateral STN-DBS in a randomized, cross-over, double-blind study (SUNDIAL Trial). Targets were chosen based on treatment of the most symptomatic side (n = 17 left hemisphere and 14 right hemisphere). All participants completed a neuropsychological battery (FAS/CFL, AVLT, DKEFS Color-Word Test) at baseline, then 2, 4, and 6 months post-surgery. Outcomes include raw scores for verbal fluency, immediate and delayed recall, and DKEFS Color-Word Inhibition trial (Trial 3) completion time. At 2, 4, and 6 months, the neurostimulation type (directional versus ring mode) was randomized for each participant. We compared baseline scores for all cognitive outcome measures using Welch’s two-sample t-tests and used linear mixed effects models to examine longitudinal effects of hemisphere and stimulation on cognition. This test battery was converted to a teleneuropsychology administration because of COVID-19 mid-study, and this was included as a covariate in all statistical models, along with years of education, baseline cognitive scores, and levodopa equivalent medication dose at each time point.Results:At baseline, patients who underwent left hemisphere implants scored lower on verbal fluency than right implants (t(20.66) = -2.49, p = 0.02). There were not significant differences between hemispheres in immediate recall (p = 0.57), delayed recall (p = 0.22), or response inhibition (p = 0.51). Post-operatively, left STN DBS patients experienced significant declines in verbal fluency over the study period (p = 0.02), while patients with right-sided stimulation demonstrated improvements (p < .001). There was no main effect of stimulation parameters (directional versus ring) on verbal fluency, memory, or inhibition, but there was a three-way interaction between time, stimulation parameters, and hemisphere on inhibition, such that left STN DBS patients receiving ring stimulation completed the inhibition trial faster (p = 0.035). After surgery, right STN DBS patients displayed faster inhibition times than patients with left implants (p = 0.015).Conclusions:Declines in verbal fluency after bilateral stimulation are the most commonly reported cognitive sequalae of DBS for movement disorders. Here we found group level declines in verbal fluency after unilateral left STN implants, but not right STN DBS up to 6 months after surgery. Patients with right hemisphere implants displayed improvements in verbal fluency. Compared to bilateral DBS, unilateral DBS surgery, particularly in the right hemisphere, is likely a modifiable risk factor for verbal fluency declines in patients with Parkinson’s disease.

Effects of bariatric surgery on cognitive function in older adults: a prospective longitudinal study.

Obesity is now well-recognized as an independent risk factor for cognitive decline. Although extensive research has been conducted on cognitive outcomes following bariatric surgery in young adults, very little is known about the impact of advanced age on the cognitive benefits of weight-loss procedures. This study aimed to assess cognitive function in older Iranian patients before and after bariatric surgery. University Hospital METHODS: In this prospective longitudinal study, 24 older adults were examined before and 4months after bariatric surgery using the Digit Span Test (DGS), the computerized version of the Wisconsin Card Sorting Test-64 (WCST-64), and the paper-and-pencil versions of the Trail Making Test (TMT), parts A and B, spanning the 4 cognitive domains of attention, working memory, processing speed, and executive functioning. The bariatric surgery group was simultaneously compared to a waiting list control group. At 4months of follow-up, comparisons between the groups revealed that the surgical group performed significantly better than the control group on the forward DGS, WCST, and TMT parts A and B. In contrast, there was no significant difference between groups on the backward DGS. Further within-group comparisons demonstrated significant improvements from baseline in forward DGS, WCST, and TMT components A and B. Nevertheless, the same variables did not alter significantly over time in the control group. The study suggests measurable cognitive benefits following bariatric surgery in older adults.

89 The Effect of Personality Traits on the Development of Predementia Cognitive States: Results from the Einstein Aging Study

Objective:Recent research has found associations between the Five Factor Model (FFM) personality traits (Openness to Experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism) and risk of developing subjective cognitive decline (SCD), mild cognitive impairment (MCI), and/or dementia. It has therefore been proposed that personality should be incorporated into conceptual models of dementia risk, as personality assessments have utility as readily available, low-cost measures to predict who is at greater risk for developing pathological cognitive decline. The objective of the present study was to explore the relationship between FFM personality traits and predementia cognitive syndromes including SCD, amnestic MCI (aMCI), and non-amnestic MCI (naMCI). The first aim was to compare baseline personality traits between participants who transitioned from healthy cognition or SCD to aMCI vs. naMCI. The second aim was to determine the relationship between FFM personality traits and risk of transition between predementia cognitive states. The third aim was to explore relationships between levels of FFM personality traits and performance on a comprehensive cognitive battery.Participants and Methods:The participants for this study were 562 (Aim 3; Mean Age = 78.90) older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment (Aims 1 & 2; Mean Age = 78.60). Baseline levels of FFM personality traits were measured in the EAS using the 50-item International Personality Item Pool (IPIP) version of the NEO-Personality Inventory. Baseline levels of anxiety and depressive symptoms, medical history, performance on a cognitive battery and age sex, and years of education were also collected. A multistate Markov approach was used to model the risk of transition across the four predementia states (cognitively healthy, SCD, aMCI, and naMCI) with each FFM personality trait as covariates.Results:Regarding Aim 1, Mann-Whitney U tests revealed no differences in levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. Regarding Aim 2, the multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, the model revealed that higher levels of extraversion were protective against developing naMCI. Finally, regarding Aim 3, exploratory correlations revealed many positive associations between levels of openness to experience and performance on neuropsychological tests. Few associations were found for the other FFM personality traits.Conclusions:Results from this study suggest that premorbid personality traits may play a predictive role in the risk for or protection against specific predementia syndromes. Thus, FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. These personality measures could be used (in addition to other established risk factors for cognitive decline) to enrich clinical trials by targeting individuals who are at greatest risk for developing specific forms of cognitive decline. Such measures may also be useful in diagnostic prediction models for predementia syndromes. These results should be replicated in future studies with larger sample sizes and younger participants.

Poster Symposium: How Well do Western Methods Used to Assess Atypical Aging in Western Countries Generalize to Sub-Saharan African Countries?

Summary Abstract:Risk factors associated with development of neurodegenerative disease has been well-studied in Western and European populations. However, there has been considerably less research in the assessment of such risk factors in developing countries, notably sub-Saharan Africa. There is a paucity of data at the micro level (e.g. neuroimaging and biomarker data) and macro level (e.g. cognitive assessment and psychosocial/environmental risk factors) for development of neurodegenerative conditions in these populations.This symposium examines Western methods of assessment of risk factors and cognitive profiles of older adults at risk for neurodegenerative disorder to determine if they are relevant to sub-Saharan African populations, specifically older Congolese adults. This symposium utilizes an older adult sample that has been comprehensively assessed both at the cellular level (via blood biomarkers and neuroimaging typically used for assessment of dementia in Western populations), to the individual functional level (via cognitive assessment), to finally, psychosocial and environmental risk factors for dementia seen at a community level. First, Dr. Ikanga will present on the association between performance on the African Neuropsychological Battery (ANB) with biomarkers specific to Alzhemer's disease and more general vascular risk factors for cognitive decline. Second, Dr. Hickle will present on structural neuroimaging data of mesial temporal lobe atrophy in comparison with performance on the ANB. Dr. Reyes will then discuss the utility of a cognitive screener developed for use in Sub-Saharan Africa on older adults from the Democratic Republic of Congo, with specific emphasis on educational corrections. Finally, Dr. De Wit will discuss health and psychosocial predictors of depressive symptoms as well as the relation between depressive symptoms and neuropsychological functioning in Congolese older adults, to determine if neurocognitive profiles are similar in Sub-Saharan Africa relative to Western populations. This "micro to macro" approach is unique in providing a comprehensive overview of risks associated with dementia in Congolese adults. This is the first study of its kind to utilize a multi-method approach for older adults at risk for dementia in Sub-Saharan Africa, and results suggest that some approaches are more valid in this population than others. Future areas of research will be discussed, as well as feasibility and validity of Western approaches in assessment of dementia to non-Western populations.

2 Contributions of Cardiovascular Disease Burden and Concussion History on Cognitive Function in Older Former National Football League Players.

Objective:Traumatic brain injury and cardiovascular disease (CVD) are modifiable risk factors for cognitive decline and dementia. Greater concussion history can potentially increase risk for cerebrovascular changes associated with cognitive decline and may compound effects of CVD. We investigated the independent and dynamic effects of CVD/risk factor burden and concussion history on cognitive function and odds of mild cognitive impairment (MCI) diagnoses in older former National Football League (NFL) players.Participants and Methods:Former NFL players, ages 50-70 (N=289; mean age=61.02±5.33 years), reported medical history and completed the Brief Test of Adult Cognition by Telephone (BTACT). CVD/risk factor burden was characterized as ordinal (0-3+) based on the sum of the following conditions: coronary artery disease/myocardial infarction, chronic obstructive pulmonary disease, hypertension, hyperlipidemia, sleep apnea, type-I and II diabetes. Cognitive outcomes included BTACT Executive Function and Episodic Memory Composite Z-scores (standardized on age- and education-based normative data), and the presence of physician diagnosed (self-reported) MCI. Concussion history was discretized into five groups: 0, 1-2, 3-5, 6-9, 10+. Linear and logistic regression models were fit to test independent and joint effects of concussion history and CVD burden on cognitive outcomes and odds of MCI. Race (dichotomized as White and Non-white due to sample distribution) was included in models as a covariate.Results:Greater CVD burden (unstandardized beta [standard error]; B=-0.10[0.42], p=.013, and race (B=0.622[0.09], p<.001), were associated with lower executive functioning. Compared to those with 0 prior concussions, no significant differences were observed for those with 1-2, 3-5, 6-9, or 10+ prior concussions (ps >.05). Race (B=0.61[.13], p<.001), but not concussion history or CVD burden, was associated with episodic memory. There was a trend for lower episodic memory scores among those with 10+ prior concussion compared to those with no prior concussions (B=-0.49[.25], p=.052). There were no significant differences in episodic memory among those with 1-2, 3-5, or 6-9 prior concussions compared to those with 0 prior concussions (ps>.05). CVD burden (B=0.35[.13], p=.008), race (greater odds in Non-white group; B=0.82[.29], p=.005), and greater concussion history (higher odds of diagnosis in 10+ group compared to those with 0 prior concussions; B=2.19[0.78], p<.005) were associated with higher odds of MCI diagnosis. Significant interaction effects between concussion history and CVD burden were not observed for any outcome (ps >.05).Conclusions:Lower executive functioning and higher odds of MCI diagnosis were associated with higher CVD burden and race. Very high concussion history (10+) was selectively associated with higher odds of MCI diagnosis. Reduction of these modifiable factors may mitigate adverse outcomes in older contact sport athletes. In former athletes, consideration of CVD burden is particularly pertinent when assessing executive dysfunction, considered to be a common cognitive feature of traumatic encephalopathy syndrome, as designated by the recent diagnostic criteria. Further research should investigate the social and structural determinants contributing to racial disparities in long-term health outcomes within former NFL players.

Tinnitus and Cognitive Decline

Tinnitus, defined as the perception of sound in the absence of any external stimuli, is a condition which affects a significant number of people worldwide. Although the pathophysiology of tinnitus is not fully understood, hearing loss is known to be a major contributor. To date, many studies have investigated the relationship between hearing loss and cognitive function, and hearing loss is now considered a modifiable risk factor for cognitive decline. In this context, recent studies have investigated whether tinnitus, which is closely associated with hearing loss, is also a risk factor for cognitive decline. However, conflicting results have been reported regarding the relationship between these two conditions. Several studies have reported cognitive decline in tinnitus patients, particularly in areas related to working memory and attention. The consideration of patient age is crucial, as older people seem to be more affected by tinnitus-related cognitive issues. In contrast, some studies have indicated no direct association between tinnitus and cognitive decline, with some even indicating potential cognitive improvement in tinnitus patients. In this article, we review the current research on the relationship between tinnitus and cognitive function and discuss the potential association between these two conditions.

The joint effects of sarcopenia and cardiometabolic risk factors on declined cognitive function: Evidence from a 7-year cohort study

BackgroundSarcopenia and cardiometabolic risk factors are very common in the middle-aged and older population. This study aimed to explore the joint effect of sarcopenia and cardiometabolic risk factors on cognitive performance and cognitive decline. MethodsThe definition of sarcopenia status was referenced in the AWGS 2019 algorithm. Linear regression models were used to explore the association of sarcopenia status with cognitive performance at baseline. Mixed effect models and multinomial logistic regression models were used to evaluate the long-term effect of sarcopenia status. The additive interaction between the effects of sarcopenia and cardiometabolic risk factors on cognitive performance was also evaluated. ResultsIn the cross-sectional analysis, sarcopenia and possible sarcopenia were associated with worse cognitive performance. In the longitudinal analysis, the participant with sarcopenia had a 0.34 [95 % CI (−0.43, −0.24)] lower global cognition score, and those with possible sarcopenia had a 0.20 [95 % CI (−0.27, −0.14)] lower global cognition score, compared with participants with no-sarcopenia. Sarcopenia and possible sarcopenia were identified as significant risk factors for cognitive decline. Sarcopenia combined with hypertension, type 2 diabetes, dyslipidemia, or abdominal obesity was associated with worse cognitive function. LimitationsThe assessment of cognitive function was not diagnosed accurately. ConclusionsSarcopenia and possible sarcopenia had adverse effects on cognitive performance and cognitive decline, sarcopenia combined with cardiometabolic risk factors can significantly enhance these effects. Therefore, the prevention of sarcopenia in the older population is crucial.

Association of Chronic Pain with Biomarkers of Neurodegeneration, Microglial Activation, and Inflammation in Cerebrospinal Fluid and Impaired Cognitive Function.

Debate surrounds the role of chronic pain as a risk factor for cognitive decline and dementia. This study aimed at examining the association of chronic pain with biomarkers of neurodegeneration using data from the Alzheimer's Disease Neuroimaging Initiative. Participants were classified using the ATN (amyloid, tau, neurodegeneration) classification. Chronic pain was defined as persistent or recurrent pain reported at baseline. For each ATN group, analysis of covariance models identified differences in cerebrospinal fluid (CSF) levels of amyloid β1-42 , phosphorylated tau 181 (ptau181 ), total tau (t-tau), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and cognitive function between chronic pain states. Differences in CSF levels of inflammatory markers between chronic pain states were further analyzed. Linear mixed effect models examined longitudinal changes. The study included 995 individuals, with 605 (60.81%) reporting chronic pain at baseline. At baseline, individuals with suspected non-Alzheimer pathophysiology and chronic pain showed increased CSF levels of t-tau and sTREM2. Chronic pain was associated with increased tumor necrosis factor α levels, irrespective of the ATN group. Longitudinally, an increase in ptau181 CSF levels was observed in chronic pain patients with negative amyloid and neurodegeneration markers. Amyloid-positive and neurodegeneration-negative chronic pain patients showed higher memory function cross-sectionally. No significant longitudinal decline in cognitive function was observed for any ATN group. Our study suggests that chronic pain induces neuronal damage and microglial activation in particular subgroups of patients along the AD spectrum. Further studies are needed to confirm these findings. ANN NEUROL 2023.

Specific quinone reductase 2 inhibitors reduce metabolic burden and reverse Alzheimer's disease phenotype in mice.

Biological aging can be described as accumulative, prolonged metabolic stress and is the major risk factor for cognitive decline and Alzheimer's disease (AD). Recently, we identified and described a quinone reductase 2 (QR2) pathway in the brain, in which QR2 acts as a removable memory constraint and metabolic buffer within neurons. QR2 becomes overexpressed with age, and it is possibly a novel contributing factor to age-related metabolic stress and cognitive deficit. We found that, in human cells, genetic removal of QR2 produced a shift in the proteome opposing that found in AD brains while simultaneously reducing oxidative stress. We therefore created highly specific QR2 inhibitors (QR2is) to enable evaluation of chronic QR2 inhibition as a means to reduce biological age-related metabolic stress and cognitive decline. QR2is replicated results obtained by genetic removal of QR2, while local QR2i microinjection improved hippocampal and cortical-dependent learning in rats and mice. Continuous consumption of QR2is in drinking water improved cognition and reduced pathology in the brains of AD-model mice (5xFAD), with a noticeable between-sex effect on treatment duration. These results demonstrate the importance of QR2 activity and pathway function in the healthy and neurodegenerative brain and what we believe to be the great therapeutic potential of QR2is as first-in-class drugs.

Basic Mechanisms of Brain Injury and Cognitive Decline in Hypertension.

Dementia affects almost 50 million adults worldwide, and remains a major cause of death and disability. Hypertension is a leading risk factor for dementia, including Alzheimer disease and Alzheimer disease-related dementias. Although this association is well-established, the mechanisms underlying hypertension-induced cognitive decline remain poorly understood. By exploring the mechanisms mediating the detrimental effects of hypertension on the brain, studies have aimed to provide therapeutic insights and strategies on how to protect the brain from the effects of blood pressure elevation. In this review, we focus on the basic mechanisms contributing to the cerebrovascular adaptions to elevated blood pressure and hypertension-induced microvascular injury. We also assess the cellular mechanisms of neurovascular unit dysfunction, focusing on the premise that cognitive impairment ensues when the dynamic metabolic demands of neurons are not met due to neurovascular uncoupling, and summarize cognitive deficits across various rodent models of hypertension as a resource for investigators. Despite significant advances in antihypertensive therapy, hypertension remains a critical risk factor for cognitive decline, and several questions remain about the development and progression of hypertension-induced cognitive impairment.

Interaction between air pollution and risk factors for cognitive decline: a comparison study in China and the UK cohorts

Interaction between air pollution and risk factors for cognitive decline: a comparison study in China and the UK cohorts

Cognitive transitions based on functional status in older adults with heart failure: a population-based study.

Cognitive impairment and functional status are both important determinants of poor outcomes in heart failure (HF). However, little is known about how functional status impacts the changes in cognitive status during the disease course. This study aimed to describe the cognitive transitions in patients with HF and assess the relationship of these transitions to functional status, which was assessed by the dependency of activities of daily living (ADL). This retrospective cohort study included 1764 patients with an International Classification of Diseases-10 code of HF (≥65years, mean age 82.3±7.9years, 39% male) from a long-term care and medical insurance database from Nobeoka city, a rural city of south-western Japan. Cognitive status at baseline and 6, 12, 18, and 24month time points was collected, and participants were stratified based on ADL status at baseline. Generalized estimating equations and multi-state modelling were used to examine associations between ADL dependency and cognitive changes/mortality. Transition probabilities were estimated using multi-state modelling. At baseline, there were 1279 (73%) and 485 (27%) patients with independent and dependent ADL, respectively. In overall patients, 1656 (93.9%) patients had normal/mild cognitive status and 108 (6%) patients had a moderate/severe cognitive status at baseline. The majority [104 (96%) patients] of patients with moderate/severe cognitive status at baseline had dependent ADL. In patients with moderate/severe cognitive status, the number of patients with dependent ADL always outnumbered that of the independent ADL throughout the follow-up. Multi-state modelling estimated that patients with dependent ADL and normal/mild cognitive status at baseline had 47% probability of maintaining the same cognitive status at 24months, while the probability of maintaining the same cognitive status was 86% for those with independent ADL. Patients with normal/mild cognitive status in the dependent ADL group at baseline had a higher risk of experiencing a transition to moderate/severe cognitive status at any time point during 24months compared with those with independent ADL [hazard ratio 5.24 (95% confidence interval 3.47-7.90)]. In older patients with HF, the prevalence of cognitive impairment was always higher for those with reduced functional status. Despite having a normal/mild cognitive status at baseline, patients with dependent ADL are at high risk of experiencing cognitive decline over 24months with substantially less chance of maintaining their cognitive status. ADL dependency was an important risk factor of cognitive decline in patients with HF.

Identifying predictors of cognitive decline in long-term care: a scoping review

BackgroundCognitive impairment can cause social, emotional, and financial burdens on individuals, caregivers, and healthcare providers. This is especially important in settings such as long-term care (LTC) homes which largely consist of vulnerable older adults. Thus, the objective of this study is to review and summarize current research examining risk factors of cognitive decline in older adults within LTC.MethodsThis scoping review includes primary observational research studies assessing within-person change in cognition over time in LTC or equivalent settings in high resource countries. A mean participant age of ≥ 65 years was required. Searches were conducted in Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PyscInfo on June 27th, 2022 and included articles published during or after the year 2000. Title, abstract, and full-text screening was performed by two independent reviewers using Covidence. Specific predictors along with their associated relation with cognitive decline were extracted by a team of reviewers into a spreadsheet.ResultsThirty-eight studies were included in this review. The mean sample size was 14 620. Eighty-seven unique predictors were examined in relation to cognitive decline. Dementia was the most studied predictor (examined by 9 of 38 studies), and the most conclusive, with eight of those studies identifying it as a risk factor for cognitive decline. Other predictors that were identified as risk factors included arterial stiffness (identified by 2 of 2 studies), physical frailty (2 of 2 studies), sub-syndromal delirium (2 of 2 studies), and undergoing the first wave of COVID-19 lockdowns (2 of 2 studies). ADL independence was the most conclusive protective factor (3 of 4 studies), followed by social engagement (2 of 3 studies). Many remaining predictors showed no association and/or conflicting results.ConclusionsDementia was the most common risk factor, while ADL independence was the most common protective factor associated with cognitive decline in LTC residents. This information can be used to stratify residents by risk severity and provide better personalized care for older adults through the targeted management of cognitive decline.

Depression, Inflammation, and Intestinal Permeability: Associations with Subjective and Objective Cognitive Functioning throughout Breast Cancer Survivorship.

About one-in-three breast cancer survivors have lingering cognitive complaints and objective cognitive impairment. Chronic inflammation and intestinal permeability (i.e., leaky gut), two risk factors for cognitive decline, can also fuel depression-another vulnerability for cognitive decline. The current study tested whether depression accompanied by high levels of inflammation or intestinal permeability predicted lower subjective and objective cognitive function in breast cancer survivors. We combined data from four breast cancer survivor studies (n = 613); some had repeated measurements for a total of 1015 study visits. All participants had a blood draw to obtain baseline measures of lipopolysaccharide binding protein-a measure of intestinal permeability, as well as three inflammatory markers that were incorporated into an inflammatory index: C-reactive protein, interleukin-6, and tumor necrosis factor-α. They reported depressive symptoms on the Center for Epidemiological Studies depression scale (CES-D), and a binary variable indicated clinically significant depressive symptoms (CES-D ≥ 16). The Kohli (749 observations) and the Breast Cancer Prevention Trial (591 observations) scales assessed subjective cognitive function. Objective cognitive function tests included the trail-making test, Hopkins verbal learning test, Conners continuous performance test, n-back test, FAS test, and animal-naming test (239-246 observations). Adjusting for education, age, BMI, cancer treatment type, time since treatment, study visit, and fatigue, women who had clinically elevated depressive symptoms accompanied by heightened inflammation or intestinal permeability reported poorer focus and marginally poorer memory. However, poorer performance across objective cognitive measures was not specific to inflammation-associated depression. Rather, there was some evidence of lower verbal fluency; poorer attention, verbal learning and memory, and working memory; and difficulties with visuospatial search among depressed survivors, regardless of inflammation. By themselves, inflammation and intestinal permeability less consistently predicted subjective or objective cognitive function. Breast cancer survivors with clinically significant depressive symptoms accompanied by either elevated inflammation or intestinal permeability may perceive greater cognitive difficulty, even though depression-related objective cognitive deficits may not be specific to inflammation- or leaky-gut-associated depression.