BACKGROUND: Depression has been found to be associated with cognitive decline, but whether longer depressive durations lead to more severe cognitive declines has not been investigated. We aimed to estimate the association between depressive duration and cognitive decline in middle-aged and older Americans based on a large-scale representative population study.
METHODS: We included 27,886 participants from the Health and Retirement Study (HRS) in 2010-2018. Four datasets with 2-, 4-, 6-, and 8-year consecutive interviews were further derived which involving persistent depressed and persistent depression-free individuals. Multiple linear regressions were constructed to estimate the effects of each depressive duration on the decline in global cognition, memory and mental status. Meta-regressions were performed to test the linear trends and to explore the heterogeneity between sex, age and baseline cognitive function along with subgroup analyses.
RESULTS: Depressive durations of 2, 4, 6, and 8 years were associated with reductions in global cognitive scores of 0.62 points (95 % CI: 0.51-0.73), 0.77 points (95 % CI: 0.60-0.94), 0.83 points (95 % CI: 0.55-1.10), and 1.09 points (95 % CI: 0.63-1.55), respectively, indicating a linear trend (P = 0.016). More pronounced associations were observed in middle-aged adults and females. Similar patterns were found in the associations between depressive duration and two subdomains, i.e., memory and mental health.
CONCLUSIONS: This study is essentially a cross-sectional study and therefore cannot provide causal associations.
CONCLUSIONS: Longer depressive durations were linearly related to more severe cognitive declines. Timely intervention for depression targeted middle-aged adults can more effectively alleviate cognition-related burdens.

BACKGROUND: Older Latino adults with HIV are at increased risk for mild cognitive impairment and earlier onset of aging-related cognitive decline. Improvements in cognitive functioning and cognitive outcomes are possible among people with HIV who adopt health promotion behaviors. However, health promotion interventions for older Latino adults with HIV have not been extensively used or widely recognized as viable treatment options. Happy Older Latinos are Active (HOLA) is a multicomponent, health promotion intervention that is uniquely tailored for older Latino adults with HIV.
OBJECTIVE: This study aims to (1) determine the feasibility and acceptability of an adapted version of HOLA aimed at improving cognitive functioning among older Latino adults with HIV; (2) explore whether HOLA will produce changes in cognitive functioning; (3) explore whether HOLA will produce changes in activity, psychosocial functioning, or biomarkers of cognition; and (4) explore whether changes in activity, psychosocial functioning or cognitive biomarkers correlate with changes in cognition, while accounting for genetic risk for dementia.
METHODS: A single-arm pilot trial with 30 Latino (aged 50 years and older) men and women with HIV was conducted to assess feasibility, acceptability, and preliminary effects on cognition. Participants were assessed at 2 time points (baseline and postintervention) on measures of neurocognitive and psychosocial functioning. In addition, blood samples were collected to determine biomarkers of cognition at baseline and postintervention. Successful recruitment was defined as meeting 100% of the targeted sample (N=30), with 20% (n=6) or less of eligible participants refusing to participate. Adequate retention was defined as 85% (n=25) or more of participants completing the postintervention assessment and acceptability was defined as 80% (n=38) or more of sessions attended by participants.
RESULTS: Participant recruitment began on February 22, 2022, and was completed on August 15, 2022. The last study visit took place on February 20, 2023. Data analysis is currently ongoing.
CONCLUSIONS: Encouraging findings from this exploratory study may provide a blueprint for scaling up the HOLA intervention to a larger cohort of older Latino adults with HIV who may be currently experiencing or are at risk for HIV-related cognitive challenges.
BACKGROUND: ClinicalTrials.gov NCT04791709; https://clinicaltrials.gov/study/NCT04791709.
UNASSIGNED: DERR1-10.2196/55507.

BACKGROUND: Whether circulating levels of sphingolipids are prospectively associated with cognitive decline and dementia risk is uncertain.
METHODS: We measured 14 sphingolipid species in plasma samples from 4488 participants (mean age 76.2 years; 40% male; and 25% apolipoprotein E (APOE) ε4 allele carriers). Cognitive decline was assessed annually across 6 years using modified Mini-Mental State Examination (3MSE) and Digital Symbol Substitution Test (DSST). Additionally, a subset of 3050 participants were followed for clinically adjudicated dementia.
RESULTS: Higher plasma levels of sphingomyelin-d18:1/16:0 (SM-16) were associated with a faster cognitive decline measured with 3MSE, in contrast, higher levels of sphingomyelin-d18:1/22:0 (SM-22) were associated with slower decline in cognition measured with DSST. In Cox regression, higher levels of SM-16 (hazard ration [HR] = 1.24 [95% confidence interval [CI]: 1.08-1.44]) and ceramide-d18:1/16:0 (Cer-16) (HR = 1.26 [95% CI: 1.10-1.45]) were associated with higher risk of incident dementia.
CONCLUSIONS: Several sphingolipid species appear to be involved in cognitive decline and dementia risk.
UNASSIGNED: Plasma levels of sphingolipids were associated with cognitive decline and dementia risk.Ceramides and sphingomyelins with palmitic acid were associated with faster annual cognitive decline and increased risk of dementia.The direction of association depended on the covalently bound saturated fatty acid chain length in analysis of cognitive decline.

UNASSIGNED: Age-related cognitive decline is accelerated by vascular risk factors for cerebral small vessel disease. However, the association of vascular risk factors with cerebral small vessel disease contributing to the sex differences in cognitive decline remains unclear.
UNASSIGNED: The purpose of this study was to evaluate sex differences in cognitive decline and the association between vascular risk factors and cognitive decline by sex.
UNASSIGNED: We used data from the UK Biobank (>55 years of age; n = 19,067) to assess cognitive tests (executive function, processing speed, and memory) while adjusting for baseline measurements to examine how vascular risk factors affect cognition. A univariate regression analysis was used to assess sex differences at the first time point (2014). A repeated measure analysis with a mixed effect model was used to determine cognitive decline (between 2014 and 2019). Any significant interaction between vascular risk factors and sex was investigated.
UNASSIGNED: Females had lower scores in all 3 domains at the first cognitive tests (2014). We found a significant sex-by-time interaction over a 5-year period in matrix pattern completion (P = 0.03). After adjusting for vascular risk factors, this interaction was reduced (P = 0.08). High low-density lipoprotein, low education, and high blood pressure had a greater effect on the rate of cognitive decline in the executive function for females compared to males for the sex∗vascular risk factor interaction (P < 0.05).
UNASSIGNED: The rate of cognitive decline did not differ significantly between males and females. However, the impact of several vascular risk factors on cognitive decline was greater in females than in males.

BACKGROUND: Falls in older adults significantly impact overall health and healthcare costs. Intrinsic capacity (IC) reflects functional reserve and is an indicator of healthy aging.
OBJECTIVE: To explore the association between IC and recent falls (≤ 90 days) in community-dwelling octogenarians from the Aging and Longevity in the Sirente geographic area (IlSIRENTE) study.
METHODS: The Minimum Data Set for Home Care (MDS-HC) and supplementary questionnaires and tests were used to assess the five IC domains: locomotion, cognition, vitality, psychology, and sensory. Scores in each domain were rescaled using the percent of maximum possible score method and averaged to obtain an overall IC score (range 0-100).
RESULTS: The study included 319 participants (mean age 85.5 ± 4.8 years, 67.1% women). Mean IC score was 80.5 ± 14.2. The optimal IC score cut-off for predicting the two-year risk of incident loss of at least one activity of daily living (ADL) was determined and validated in a subset of 240 individuals without ADL disability at baseline (mean age 84.7 ± 4.4 years, 67.1% women). Participants were then stratified into low (< 77.6) and high (≥ 77.6) IC categories. Those with high IC (63.9%) were younger, more often males, and had lower prevalence of recent falls, disability, multimorbidity, and polypharmacy. Logistic regression models including IC as a continuous variable revealed a significant association between higher IC and lower odds of falls. This association was significant in the unadjusted (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.94-0.98, p < 0.001), age- and sex-adjusted (OR 0.96, 95% CI 0.94-0.98, p < 0.001), and fully adjusted models (OR 0.96, 95% CI 0.93-0.99, p = 0.003). When considering IC as a categorical variable, unadjusted logistic regression showed a strong association between high IC and lower odds of falls (OR 0.31, 95% CI 0.16-0.60, p < 0.001). This association remained significant in both the age- and sex-adjusted (OR 0.30, 95% CI 0.15-0.59, p < 0.001) and fully adjusted models (OR 0.33, 95% CI 0.16-0.82, p = 0.007). The locomotion domain was independently associated with falls in the unadjusted (OR 0.98, 95% CI 0.97-0.99, p < 0.001), age- and sex-adjusted (OR 0.97, 95% CI 0.96-0.99, p < 0.001), and fully adjusted model (OR 0.98, 95% CI 0.96-0.99, p < 0.001).
CONCLUSIONS: This is the first study using an MDS-HC-derived instrument to assess IC. Individuals with higher IC were less likely to report recent falls, with locomotion being an independently associated domain.
CONCLUSIONS: Lower IC is linked to increased odds of falls. Interventions to maintain and improve IC, especially the locomotion domain, may reduce fall risk in community-dwelling octogenarians.

BACKGROUND: Our current understanding of how computerized brain training drives cognitive and functional benefits remains incomplete. This paper describes the protocol for Improving Neurological Health in Aging via Neuroplasticity-based Computerized Exercise (INHANCE), a randomized controlled trial in healthy older adults designed to evaluate whether brain training improves cholinergic signaling.
OBJECTIVE: INHANCE evaluates whether 2 computerized training programs alter acetylcholine binding using the vesicular acetylcholine transporter ligand [18F] fluoroethoxybenzovesamicol ([18F] FEOBV) and positron emission tomography (PET).
METHODS: In this phase IIb, prospective, double-blind, parallel-arm, active-controlled randomized trial, a minimum of 92 community-dwelling healthy adults aged 65 years and older are randomly assigned to a brain training program designed using the principles of neuroplasticity (BrainHQ by Posit Science) or to an active control program of computer games designed for entertainment (eg, Solitaire). Both programs consist of 30-minute sessions, 7 times per week for 10 weeks (35 total hours), completed remotely at home using either loaned or personal devices. The primary outcome is the change in FEOBV binding in the anterior cingulate cortex, assessed at baseline and posttest. Exploratory cognitive and behavioral outcomes sensitive to acetylcholine are evaluated before, immediately after, and 3 months following the intervention to assess the maintenance of observed effects.
RESULTS: The trial was funded in September 2019. The study received approval from the Western Institutional Review Board in October 2020 with Research Ethics Board of McGill University Health Centre and Health Canada approvals in June 2021. The trial is currently ongoing. The first participant was enrolled in July 2021, enrollment closed when 93 participants were randomized in December 2023, and the trial will conclude in June 2024. The study team will be unblinded to conduct analyses after the final participant exits the study. We expect to publish the results in the fourth quarter of 2024.
CONCLUSIONS: There remains a critical need to identify effective and scalable nonpharmaceutical interventions to enhance cognition in older adults. This trial contributes to our understanding of brain training by providing a potential neurochemical explanation of cognitive benefit.
BACKGROUND: ClinicalTrials.gov NCT04149457; https://clinicaltrials.gov/ct2/show/NCT04149457.
UNASSIGNED: DERR1-10.2196/59705.

OBJECTIVE: Hyperlipidemia and postoperative delirium (POD) significantly affect patients\' quality of life; however, the question of whether hyperlipidemia constitutes a risk factor for POD remain unclear. This study aimed to investigate whether patients with hyperlipidemia face elevated risks of developing POD and to identify potential causes for this increased risk.
METHODS: A prospective cohort study.
METHODS: Operating room.
METHODS: Patients were adults scheduled for colorectal cancer surgery in 2023.
METHODS: The exposure factor was hyperlipidemia, and the patients were divided into hyperlipidemia group and non-hyperlipidemia group.
METHODS: POD occurrence within three days post-surgery was assessed using the 3-Minute Diagnostic Interview for Confusion Assessment Method. Over one year, these patients were monitored through telephone to evaluate their survival and cognitive function. Logistic regression analysis was performed to evaluate the risk factors for POD development in patients with hyperlipidemia and to construct a clinical prediction model.
RESULTS: This study included 555 patients. POD incidence was 21.6% in the hyperlipidemia group and 12.7% in the non-hyperlipidemia group. One year following surgery, patients with hyperlipidemia and POD exhibited significantly higher rates of mortality and cognitive decline than did those without POD (p < 0.001). A multifactorial logistic clinical prediction model was constructed from seven independent risk factors for POD development in patients with hyperlipidemia, including education, preoperative total cholesterol (TC), preoperative triglyceride (TG), diet, history of hypertension, Sedation-Agitation Scale, and postoperative trimethylamine N-oxide expression level, and it had the highest predictive value for POD development in patients with hyperlipidemia.
CONCLUSIONS: Compared with those without hyperlipidemia, patients with hyperlipidemia had higher POD incidence. Elevated serum TC and TG levels are independent risk factors for POD in patients with hyperlipidemia. The study\'s findings could help develop strategies for improving POD and hyperlipidemia treatment.

The predictive abilities of computer-based screening devices for early cognitive decline (CD) in older adults have rarely been longitudinally examined. Therefore, this study examined the ability of CogEvo, a short-duration, computer-based cognitive screening device requiring little professional involvement, to predict CD among community-dwelling older adults. We determined whether 119 individuals aged ≥ 65 years living in Japanese rural communities who scored ≥ 24 on the Mini-Mental State Examination (MMSE) at baseline developed CD by annually administering the MMSE to them. CD was defined as an MMSE score of ≤23. At baseline, the overall CogEvo judgment grade, with lower grades indicating better cognitive function, was calculated from the results of various cognitive tasks. Over 2 years, 10 participants developed CD. Participants with grades of 4 had a higher percentage of CD cases than those with grades of ≤3 (p < 0.01). This relationship remained significant after controlling for possible confounders, including the MMSE score at baseline. The sensitivity and specificity of the CogEvo grade cutoff of 4 were 50.0% and 93.6%, respectively. In conclusion, CogEvo may be an efficient tool for identifying individuals at a high risk for dementia. The possibility of missing CD cases should be considered when using CogEvo for screening.

BACKGROUND: School-based social support for Black students may mediate or modify the association between school segregation and late-life cognition.
METHODS: Study of Healthy Aging in African Americans participants (n = 574) reported segregated school attendance and school-based social support. Associations of segregated schooling with domain-specific cognitive outcomes and effect modification or mediation by school-based social support were evaluated with linear mixed models.
RESULTS: Segregated school attendance was associated with increased likelihood of school-based social support. Segregated (vs. desegregated in 6th grade) school attendance was associated with lower executive function (β = -0.18 [-0.34, -0.02]) and semantic memory z-scores (β = -0.31 [-0.48, -0.13]). Social support did not mediate these associations. Estimates for segregated school attendance were attenuated among those who felt supported, although there was limited evidence of statistically significant effect modification.
CONCLUSIONS: Early-childhood school segregation was associated with poorer cognitive function. Sources of resilience within racialized educational experiences should be further evaluated to bridge inequities.
CONCLUSIONS: School segregation is a form of structural racism that affected the educational experiences of Black youth with potentially lasting consequences for healthy brain aging. Black students who attended a segregated school experienced greater school-based social support, which may highlight a potential source of resilience and resistance against the effects of racism-related stressors on cognitive function. The estimated adverse association between attending a segregated school on cognition was larger for students without an adult at school who cared about them versus those with an adult at school who cared about them, but estimates were imprecise.

Vitamin B12 deficiency can present with a variety of neurological and cognitive symptoms. Especially in elderly patients, vitamin B12 deficiency can be easily overlooked because symptoms may be attributed to comorbid conditions or solely to the aging process. In this case study, we present two patients, a 71-year-old man and a 74-year-old female, with vitamin B12 deficiency. The male patient had a history of (partial) resection of the ileum/jejunum/colon because of intestinal ischemia. The female patient had a history of hypothyroidism, type 2 diabetes with complications (including peripheral neuropathy), mitochondrial myopathy, and chronic lymphocytic leukemia. Both patients presented with severe fatigue, cognitive impairment, and impaired walking. Next to this, the male patient suffered from depressive symptoms and mild disorientation, and the female patient experienced neuropathic pain. She also mentioned a positive family history for B12 deficiency. The first patient had normal to high B12 levels because he was already on B12 injections (once every three weeks) because of an earlier diagnosed B12 deficiency. The female patient had B12 levels within normal range (holotranscobalamin 54 pmol/L) and her diagnosis was confirmed by elevated homocysteine and methylmalonic acid levels. Treatment with frequent hydroxocobalamin injections and other supplements significantly improved their cognitive, emotional, and motor functions. These cases underscore the need for a high level of clinical suspicion in elderly patients, also in cases of normal B12 levels but with clinical signs of deficiency and a positive risk factor, such as stomach or small bowel surgery or positive family history.
Plain language titleA case study of two elderly patients with vitamin B12 deficiency and neurological and cognitive complaintsPlain language summaryVitamin B12 deficiency in elderly patients can be easily overlooked as symptoms can also be caused by other age-related diseases or the aging process. In our article we present two elderly patients, a 71-year-old male and a 74-year-old female, with neurological complaints, such as severe fatigue, cognitive decline, and walking impairment. The male patient had a history of small bowel surgery, and the female patient mentioned that she had several siblings with B12 deficiency. Additionally, the male patient suffered from depressive symptoms and mild disorientation, and the female had severe pain in her legs. The male patient already received B12 injections because of an earlier B12 diagnosis, but with a relatively low frequency. The B12 levels of the female patients were within the normal range. However, her diagnoses could be confirmed with additional laboratory measurements, such as homocysteine and methylmalonic acid. Treatment with frequent B12 injections and other supplements significantly improved their cognitive, emotional, and motor functions. Our study shows that clinicians should carefully consider the possibility of B12 deficiency in elderly patients with cognitive and neurological complaints, also in patients with B12 levels within the normal range, but with risk factors such as family members with B12 deficiency or conditions that may impair the vitamin B12 uptake, such as previous stomach or small bowel surgery.