Assessing rapid spatial working memory in community-living older adults in a virtual adaptation of the rodent water maze paradigm.

Aging often leads to a decline in various cognitive domains, potentially contributing to spatial navigation challenges among older individuals. While the Morris water maze is a common tool in rodents research for evaluating allocentric spatial memory function, its translation to studying aging in humans, particularly its association with hippocampal dysfunction, has predominantly focused on spatial reference memory assessments. This study expanded the adaptation of the Morris water maze for older adults to assess flexible, rapid, one-trial working memory. This adaptation involved a spatial search task guided by allocentric cues within a 3-D virtual reality (VR) environment. The sensitivity of this approach to aging was examined in 146 community-living adults from three Chinese cities, categorized into three age groups. Significant performance deficits were observed in participants over 60 years old compared to younger adults aged between 18 and 43. However, interpreting these findings was complicated by factors such as psychomotor slowness and potential variations in task engagement, except during the probe tests. Notably, the transition from the 60 s to the 70 s was not associated with a substantial deterioration of performance. A distinction only emerged when the pattern of spatial search over the entire maze was examined in the probe tests when the target location was never revealed. The VR task's sensitivity to overall cognitive function in older adults was reinforced by the correlation between Montreal Cognitive Assessment (MoCA) scores and probe test performance, demonstrating up to 17 % shared variance beyond that predicted by chronological age alone. In conclusion, while implementing a VR-based adaptation of rodent water maze paradigms in older adults was feasible, our experience highlighted specific interpretative challenges that must be addressed before such a test can effectively supplement traditional cognitive assessment tools in evaluating age-related cognitive decline.

Factors influencing physical activity behavior in older adults with subjective cognitive decline: an empirical study using SEM and fsQCA methods.

Objectives: Despite the evident potential benefits of engaging in physical activity (PA) for older adults with subjective cognitive decline (SCD), their PA levels remains low. Previous research has predominantly focused on PA behaviors in individuals with dementia/mild cognitive impairment, with limited attention given to those with SCD. Therefore, this study aims to identify key factors influencing PA behavior in older adults with SCD based on the Self-Determination Theory (SDT) and the capability-opportunity-motivation (COM-B) model. Methods: Three hundred and three individuals aged 60 and above with SCD participated in this study. A face-to-face structured questionnaire survey was conducted. Data were analyzed using Structural Equation Modeling (SEM) and Fuzzy Set Qualitative Comparative Analysis (fsQCA). Results: SEM results indicate that PA social support primarily influences PA behavior through three indirect pathways: the separate mediating effect of basic psychological needs, the separate mediating effect of motivation, and the chained mediating effect of both. Physical literacy, on the other hand, influences PA behavior through the separate mediating effect of motivation. Necessary conditions analysis by fsQCA reveals that no single factor is necessary for promoting PA behavior in older adults with SCD, while sufficiency analysis identifies four different combinations of factors leading to PA behavior. Conclusion: The model derived from the framework of SDT and the COM-B model effectively explains and predicts the interrelationships among variables. Physical activity behavior in older individuals with SCD is the result of multifactorial synergies.

Citrus supplementation in subjective cognitive decline: results of a 36-week, randomized, placebo-controlled trial.

BACKGROUND: Developing interventions for older adults with subjective cognitive decline (SCD) has the potential to prevent dementia in this at-risk group. Preclinical models indicate that Citrus-derived phytochemicals could benefit cognition and inflammatory processes, but results from clinical trials are still preliminary. The aim of this study is to determine the effects of long-term supplementation with Citrus peel extract on cognitive performance and inflammation in individuals with SCD. METHODS: Eighty participants were randomly assigned to active treatment (400 mg of Citrus peel extract containing 3.0 mg of naringenin and 0.1 mg of auraptene) or placebo at 1:1 ratio for 36 weeks. The primary endpoint was the change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score across the 36-week trial period. Other cognitive outcomes included tests and scales evaluating verbal memory, attention, executive and visuospatial functions, and memory concerns. The secondary endpoint was the change of interleukin-8 (IL-8) levels over the 36-week trial period in a subsample of 60 consecutive participants. An Intention-to-treat approach with generalized linear mixed models was used for data analysis. RESULTS: The RBANS total score showed significant improvement in both Citrus peel extract and placebo groups at 36 weeks (p for time < .001, d = 0.36, p time x treatment = .910). Significant time effects were also found in cognitive domains of short- and long-term verbal memory (p < .001) and scales of subjective memory (p < .01), with no significant time x treatment interaction. The largest effect sizes were observed in verbal memory in the placebo group (d = 0.69 in short-term, and d = 0.78 in long-term verbal memory). Increased IL-8 levels were found at 36-week follow-up in both Citrus peel extract and placebo groups (p for time = .010, d = 0.21, p time x treatment = .772). Adverse events were balanced between groups. CONCLUSIONS: In this randomized clinical trial, long-term Citrus peel extract supplementation did not show cognitive benefits over placebo in participants with SCD, possibly due to high placebo response. These findings might have specific implications for designing future nutraceutical trials in individuals experiencing SCD. TRIAL REGISTRATION: The trial has been registered at the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT04744922 on February 9th, 2021 ( https://www. CLINICALTRIALS: gov/ct2/show/NCT04744922 ).

Exploring the Association Between Cognitive Decline and Triglyceride-Glucose Index: A Systematic Review and Meta-Analysis.

BACKGROUND: Cognitive decline and dementia are debilitating conditions that compromise the quality of life and charge the healthcare system with a substantial socioeconomic burden. In this context, emerging evidence supports an association between the triglyceride-glucose index (TyG), a surrogate insulin resistance marker, and cognitive decline and dementia. Hence, we systematically reviewed the studies assessing the TyG index in patients with cognitive decline and their controls. METHODS: Online international databases (PubMed, Scopus, Embase, and the Web of Science) were searched comprehensively for studies showing the TyG index in patients with cognitive decline/impairment. Random-effect meta-analyses were conducted to calculate the standardized mean difference (SMD), pooled odds ratio (OR), and pooled area under the curve (AUC), in addition to 95% confidence intervals (CIs) for the comparisons of groups. RESULTS: Seventeen studies were included in our analysis. Then, we conducted a meta-analysis, demonstrating that patients with cognitive decline had significantly higher levels of TyG index than those without (SMD 0.83, 95% CI 0.16 to 1.50, p = 0.015). Moreover, our data showed that a 1-unit increase in the TyG index was associated with higher odds of cognitive decline (adjusted OR [aOR] 2.86, 95% CI 1.49 to 5.50, p = 0.002). Further, we observed that patients in the fourth TyG quartile with higher values of the TyG index than the first quartile presented with more increased cognitive decline (aOR 1.62, 95%CI 1.11 to 2.38, p = 0.013). Finally, pooled AUC data for the diagnostic performance of the TyG index resulted in an overall AUC value of 0.73 (95% CI 0.66 to 0.79). Sensitivity and specificity were also calculated as 0.695 and 0.687, respectively. CONCLUSION: This study supports the clinical utility of the TyG index in patients with cognitive decline and solicits more focused studies to consolidate its usage in clinical settings and real-world practice.

Non-Alzheimer's amnestic mild cognitive impairment with medial temporal hypometabolism.

INTRODUCTION: The increasing use of Alzheimer's disease (AD) biomarkers has led to the recognition of a subgroup of non-AD amnestic mild cognitive impairment (aMCI) patients who have medial temporal hypometabolism on fluorodeoxyglucose-positron emission tomography (FDG-PET). METHODS: In this academic memory-clinic-based consecutive series, 16 non-AD aMCI patients and 28 AD controls matched for sex, age, and baseline Mini-Mental State Examination (MMSE) were followed for a median duration of 4.5 years. Our primary outcome was the MMSE decline rate over the subsequent years. We also determined the final diagnosis over time. RESULTS: FDG-PET showed more pronounced medial temporal hypometabolism in non-AD cases and more inferior parietal lobule hypometabolism in AD controls. MMSE decline was slower in non-AD (ß = -0.51) than in AD (ß = -2.00) patients. Five non-AD cases developed frontotemporal dementia years after symptom onset, and one developed dementia with Lewy bodies. DISCUSSION: Non-AD aMCI patients with medial temporal hypometabolism show slower cognitive decline. Highlights: Non-AD aMCI with medial temporal hypometabolism shows slower cognitive decline than AD.FDG-PET revealed distinct metabolic patterns between non-AD aMCI and AD patients.Approximately one-third of non-AD aMCI cases developed frontotemporal dementia.Comprehensive diagnostic biomarkers are crucial for non-AD aMCI characterization.

Individualized and Biomarker-Based Prognosis of Longitudinal Cognitive Decline in Early Symptomatic Alzheimer's Disease.

Background: Although individualized models using demographic, MRI, and biological markers have recently been applied in mild cognitive impairment (MCI), a similar study is lacking for patients with early Alzheimer's disease (AD) with biomarker evidence of abnormal amyloid in the brain. Objective: We aimed to develop prognostic models for individualized prediction of cognitive change in early AD. Methods: A total of 421 individuals with early AD (MCI or mild dementia due to AD) having biomarker evidence of abnormal amyloid in the brain were included in the current study. The primary cognitive outcome was the slope of change in Alzheimer's Disease Assessment Scale-cognitive subscale-13 (ADAS-Cog-13) over a period of up to 5 years. Results: A model combining demographics, baseline cognition, neurodegenerative markers, and CSF AD biomarkers provided the best predictive performance, achieving an overfitting-corrected R2 of 0.59 (bootstrapping validation). A nomogram was created to enable clinicians or trialists to easily and visually estimate the individualized magnitude of cognitive change in the context of patient characteristics. Simulated clinical trials suggested that the inclusion of our nomogram into the enrichment strategy would lead to a substantial reduction of sample size in a trial of early AD. Conclusions: Our findings may be of great clinical relevance to identify individuals with early AD who are likely to experience fast cognitive deterioration in clinical practice and in clinical trials.

Efficacy of community groups as a social prescription for senior health-insights from a natural experiment during the COVID-19 lockdown.

Loneliness and associated physical and cognitive health decline among the aging population is an important medical concern, exacerbated in times of abnormal isolation like the 2020-2021 Covid-19 pandemic lockdown. In this backdrop, recent "social prescribing" based health policy initiatives such as community groups as a support structure for the aging population assumes great importance. In this paper, we evaluate and quantify the impact of such social prescribing policies in combatting loneliness and related health degeneration of the aging population in times of abnormal isolation. To this end, we conduct a natural experiment across a sample of 618 individuals aged 65 and over with varying access to community groups during the Covid-19 lockdown period. Using a random-effects, probit model to compare the differences in health outcomes of participants with access to community groups (target) with those without access (control), we find that the target group was 2.65 times less likely to suffer from loneliness as compared to the control group, along with lower incidences of reported cardiovascular and cognitive health decline. These initial findings provide preliminary support in favor of the interventional power of social prescription tools in mitigating loneliness and its consequent negative health impact on the aging population.

Plasma neurofilament light chain as prognostic marker of cognitive decline in neurodegenerative diseases, a clinical setting study.

BACKGROUND: Analysis of selected research cohorts has highlighted an association between plasma neurofilament light (NfL) protein and cross-sectional cognitive impairment as well as longitudinal cognitive decline. However, the findings have yielded inconsistent results regarding its possible application in clinical practice. Despite its potential prognostic significance, the role of plasma NfL in daily clinical practice with unselected patients suffering from cognitive impairment remains largely unexplored. METHODS: This retrospective, cross-sectional and longitudinal monocentric study enrolled 320 patients with Alzheimer's disease ([AD], n = 158), dementia with Lewy body ([DLB], n = 30), frontotemporal dementia ([FTD], n = 32), non-neurodegenerative diseases ([NND], n = 59) or subjective cognitive decline ([SCD], n = 41). Plasma NfL levels were measured at baseline on the Simoa platform. AD, DLB, and FTD patients were also analyzed altogether as a 'degenerative conditions' subgroup, whereas SCD and NND were grouped as a 'non-degenerative conditions' subgroup. We assessed the relationship between plasma NfL levels and cross-sectional cognitive performance, including global cognition and six specific cognitive domains. A subset of 239 patients had follow-up mini-mental state examinations (MMSE) up to 60 months. Models were adjusted on age, education level, glomerular filtration rate and body mass index. RESULTS: In 320 patients, baseline plasma NfL levels were negatively associated with global cognition (ß=-1.28 (-1.81 ; -0.75) P < 0.001), memory (ß=-1.48 (-2.38 ; -0.59), P = 0.001), language (ß=-1.72(-2.49 ; -0.95) P < 0.001), praxis (ß=-2.02 (-2.91 ; -1.13) P < 0.001) and executive functions (ß=-0.81, P < 0.001). Across diagnosis, plasma NfL levels were negatively associated with cross-sectional global cognition in all but the SCD subgroup, specifically with executive functions and memory in AD (respectively ß=-0.71(-1.21 ; -0.211), P = 0.005 and ß=-1.29 (-2.17 ; -0.42), P = 0.004), and with attention in LBD (ß=-0.81(-1.16 ; -0.002), P = 0.03). Linear mixed-effects models showed that plasma NfL predicted MMSE decline in the global population (ßPlasmaNfLxTime=-0.15 (-0.26 ; -0.04), P = 0.006), as in the neurodegenerative condition subgroup (ßPlasmaNfLxTime=-0.21 (-0.37 ; - 0.06), P = 0.007), but not in non-neurodegenerative condition subgroup. CONCLUSION: In our clinical cohort, plasma NfL was associated with faster cognitive decline in neurodegenerative dementia, which corroborates data obtained in research cohorts. Yet, plasma NfL was not predictive of accelerated cognitive decline in individuals without neurodegeneration, suggesting its use as a neurodegeneration-specific predictive biomarker.

Abnormal resting-state functional connectivity of hippocampal subregions in type 2 diabetes mellitus-associated cognitive decline.

Objective: Type 2 diabetes mellitus (T2DM) over time predisposes to inflammatory responses and abnormalities in functional brain networks that damage learning, memory, or executive function. The hippocampus is a key region often reporting connectivity abnormalities in memory disorders. Here, we investigated peripheral inflammatory responses and resting-state functional connectivity (RSFC) changes characterized of hippocampal subregions in type 2 diabetes-associated cognitive decline (T2DACD). Methods: The study included 16 patients with T2DM, 16 patients with T2DACD and 25 healthy controls (HCs). Subjects were assessed for cognitive performance, tested for the expression of inflammatory factors IL-6, IL-10 and TNF-α in peripheral serum, underwent resting-state functional magnetic resonance imaging scans, and analyzed for RSFC using the hippocampal subregions as seeds. We also calculated the correlation between cognitive performance and RSFC of hippocampal subregion, and analyzed the significantly altered RSFC values of T2DACD for Receiver Operating Characteristic (ROC) analysis. Results: T2DACD patients showed a decline in their ability to complete cognitive assessment scales and experimental paradigms, and T2DM did not show abnormal cognitive performance. IL-6 expression was increased in peripheral serum in both T2DACD and T2DM. Compared with HCs, T2DACD showed abnormalities RSFC of the left anterior hippocampus with left precentral gyrus and left angular gyrus. T2DM showed abnormalities RSFC of the left middle hippocampus with right medial frontal gyrus, right anterior and middle hippocampus with left precuneus, left anterior hippocampus with right precuneus and right posterior middle temporal gyrus. Compared with T2DM, T2DACD showed abnormalities RSFC of the left posterior hippocampus and right middle hippocampus with left precuneus. In addition, RSFC in the left posterior hippocampus with left precuneus of T2DACD was positively correlated with Flanker conflict response time (r=0.766, P=0.001). In the ROC analysis, the significantly altered RSFC values of T2DACD achieved significant performance. Conclusions: T2DACD showed a significant decrease in attentional inhibition and working memory, peripheral pro-inflammatory response increased, and abnormalities RSFC of the hippocampal subregions with default mode network and sensory-motor network. T2DM did not show a significant cognitive decline, but peripheral pro-inflammatory response increased and abnormalities RSFC of the hippocampus subregions occurred in the brain. In addition, the left precuneus may be a key brain region in the conversion of T2DM to T2DACD. The results of this study may provide a basis for the preliminary diagnosis of T2DACD.

Mind Language Disturbances and PET-Signs of Depression vs Alzheimer's Disease: Are There Any Common Patterns Identified?

BACKGROUND: There is a broad appreciation that a diagnosis of depression (D) in the elderly is a strong risk factor for incident dementia, particularly Alzheimer's disease (AD). Indeed, the two disorders might constitute a dyad, although their causal relationship is uncertain, given the likely bidirectional and compounding effects of social withdrawal and loss of previous activities, and the manifestation of language disturbances, cognitive dysfunction, and social disruption that are typical of both conditions. We argue that language declines in D and AD share common patterns and biological underpinnings, and that D/AD patients might benefit from intensive language remediation training aiming to improve the functioning of neural networks that are linked to similar cognitive impairments. METHODS: A literature search in PubMed database included topics of language disturbances, cognitive impairments, and molecular brain imaging by positron emission tomography (PET) to identify common patterns in D and AD regarding language decline and its neurobiological underpinnings. RESULTS: Language disturbances show a particular commonality in the two disorders, manifesting in simplified language and particular speech markers (e.g., lexical and semantic repetitions, arguably due to ruminations in D and memory deficits in AD). PET can reveal abnormal protein deposits that are practically diagnostic of AD, but cerebrometabolic deficits to PET with the glucose tracer FDG show a certain commonality in D and AD. Typical findings of hypometabolism in the frontal lobes doubtless underlie the executive function deficits, where frontal hypometabolism in prodromal D increases with AD progression. This may reflect overlapping changes in noradrenaline and other neurotransmitter (e.g. serotonin) changes. Cerebrometabolic deficits associated with language dysfunction may inform targeted language remediation treatments in the D/AD progression. CONCLUSIONS: Language remediation techniques targeting specific language disturbances might present an important complimentary treatment strategy along with an adjusted pharmacotherapy approach and standard psychosocial rehabilitation interventions. We see a need for investigations of language remediation informed by the overlapping pathologies and language disturbances in D and AD.

An effective screening model for subjective cognitive decline in community-dwelling older adults based on gait analysis and eye tracking.

Objective: To evaluate the effectiveness of multimodal features based on gait analysis and eye tracking for elderly people screening with subjective cognitive decline in the community. Methods: In the study, 412 cognitively normal older adults aged over 65 years were included. Among them, 230 individuals were diagnosed with non-subjective cognitive decline and 182 with subjective cognitive decline. All participants underwent assessments using three screening tools: the traditional SCD9 scale, gait analysis, and eye tracking. The gait analysis involved three tasks: the single task, the counting backwards dual task, and the naming animals dual task. Eye tracking included six paradigms: smooth pursuit, median fixation, lateral fixation, overlap saccade, gap saccade, and anti-saccade tasks. Using the XGBoost machine learning algorithm, several models were developed based on gait analysis and eye tracking to classify subjective cognitive decline. Results: A total of 161 gait and eye-tracking features were measured. 22 parameters, including 9 gait and 13 eye-tracking features, showed significant differences between the two groups (p < 0.05). The top three eye-tracking paradigms were anti-saccade, gap saccade, and median fixation, with AUCs of 0.911, 0.904, and 0.891, respectively. The gait analysis features had an AUC of 0.862, indicating better discriminatory efficacy compared to the SCD9 scale, which had an AUC of 0.762. The model based on single and dual task gait, anti-saccade, gap saccade, and median fixation achieved the best efficacy in SCD screening (AUC = 0.969). Conclusion: The gait analysis, eye-tracking multimodal assessment tool is an objective and accurate screening method that showed better detection of subjective cognitive decline. This finding provides another option for early identification of subjective cognitive decline in the community.

Cerebral Proteomic Changes in the rTg-D Rat Model of Cerebral Amyloid Angiopathy Type-2 With Cortical Microhemorrhages and Cognitive Impairments.

Cerebral amyloid angiopathy (CAA) is a common disorder of the elderly, a prominent comorbidity of Alzheimer's disease, and causes vascular cognitive impairment and dementia. Previously, we generated a novel transgenic rat model (rTg-D) that produces human familial CAA Dutch E22Q mutant amyloid ß-protein (Aß) in brain and develops arteriolar CAA type-2. Here, we show that deposition of fibrillar Aß promotes arteriolar smooth muscle cell loss and cerebral microhemorrhages that can be detected by magnetic resonance imaging and confirmed by histopathology. Aged rTg-D rats also present with cognitive deficits. Cerebral proteomic analyses revealed 241 proteins that were significantly elevated with an increase of >50% in rTg-D rats presenting with CAA compared to wild-type rats. Fewer proteins were significantly decreased in rTg-D rats. Of note, high temperature requirement peptidase A (HTRA1), a proteinase linked to transforming growth factor beta 1 (TGF-ß1) signaling, was elevated and found to accumulate in cerebral vessels harboring amyloid deposits. Pathway analysis indicated elevation of the TGF-ß1 pathway and increased TGF-ß1 levels were detected in rTg-D rats. In conclusion, the present findings provide new molecular insights into the pathogenesis of CAA and suggest a role for interactions between HTRA1 and TGF-ß1 in the disease process.

Neuroprotective effects of magnesium: implications for neuroinflammation and cognitive decline.

Neurodegenerative diseases, which are characterized by progressive neuronal loss and cognitive decline, are a significant concern for the aging population. Neuroinflammation, a shared characteristic of these diseases, is implicated in their pathogenesis. This article briefly summarizes the role of magnesium, an essential mineral involved in numerous enzymatic reactions and critical for neuronal bioactivity, in the context of neuroinflammation and cognitive decline. The potential neuroprotective effects of magnesium, including the mechanisms of neuroprotection by magnesium through maintaining neuronal ion homeostasis, reducing inflammation, and preventing excitotoxicity, are also described. Additionally, we discuss the impact of inadequate magnesium on neuroinflammation and its potential as a therapeutic agent for attenuating cognitive decline to improve neurodegenerative conditions.

Comparison of brief olfactory and cognitive assessments to neuroimaging biomarkers in the prediction of cognitive decline and dementia in the MCSA cohort.

INTRODUCTION: We evaluated impaired odor identification and global cognition as simple, cost-effective alternatives to neuroimaging biomarkers to predict cognitive decline and dementia in the Mayo Clinic Study of Aging. METHODS: Six hundred forty-seven participants (mean 8.1, standard deviation 3.4 years' follow-up) had the following baseline procedures: modified Blessed Information Memory Concentration Test (BIMCT), 12-item Brief Smell Identification Test (BSIT), structural brain magnetic resonance imaging (MRI), and positron emission tomography (PET) imaging with 11C-Pittsburgh compound B (11C-PiB) and fluorodeoxyglucose (FDG; subset). RESULTS: Cognitive decline developed in 102 participants and dementia in 34 participants. In survival analyses, PiB PET showed robust prediction for cognitive decline. Impaired BSIT, impaired BIMCT, MRI, and FDG measures were also significant predictors. The combination of demographics + BSIT + BIMCT showed strong predictive utility (C-index 0.81), similar to demographics + PiB PET (C-index 0.80). Similar but stronger results were obtained for prediction of dementia. DISCUSSION: Impairment in both odor identification test and global cognition was comparable to PiB PET for predicting cognitive decline and dementia. HIGHLIGHTS: In 647 participants in the population-based Mayo Clinic Study of Aging, several clinical markers and biomarkers each predicted cognitive decline or dementia during an average 8 years of follow-up. The combination of the demographic variables of age, sex, and education with a brief odor identification test (BSIT) and a global cognitive test (Blessed Information Memory Concentration Test) showed strong predictive utility (C-index 0.81) for cognitive decline that was similar to the demographic variables combined with Pittsburgh Compound B amyloid imaging (C-index 0.80). Combining a brief odor identification test with a brief cognitive test needs consideration as a simple, cost-effective option in the clinical assessment of individuals at risk of cognitive decline and dementia, as well as a potential tool to identify individuals who may benefit from disease-modifying treatments and to screen participants for prevention trials.

Associations of benzodiazepine use with cognitive ability and age-related cognitive decline.

BACKGROUND: It remains uncertain whether long-term use of benzodiazepines is associated with age-related cognitive decline, and if cognitive ability in early life is the driver of any association. This study examines the association of cognitive ability in young adulthood with later use of benzodiazepines and explores whether the use of benzodiazepines during adult life is associated with cognitive decline in late midlife. METHODS: The study samples include cognitive tests on the Børge Priens Prøve (BPP) from the conscription board examination (age 19 years) from 335 513 men born 1949-1961 and data from re-examinations of 5183 men 44 years later. Cognitive decline was defined as the difference between scores at the conscription board and the re-examination. Information on purchases of benzodiazepines was obtained from the Danish National Prescription Registry, 1995-2022. Associations were analysed using Cox proportional hazards and linear regression. RESULTS: In total, 120 911 (36%) men purchased benzodiazepines during a follow-up of 20 years. Lower cognitive scores in young adulthood were associated with a higher risk of initiating benzodiazepines (hazard ratio [95% CI] = 0.71[0.68-0.75]). Men with the highest cumulative use of benzodiazepines had larger cognitive decline (ß-coefficient [95% CI] = -1.66 [-2.09 to -1.23] BPP scores) compared with never users. Current benzodiazepine users showed a larger cognitive decline than never users (ß-coefficient [95% CI] = -2.42[-3.18 to -1.66] BPP scores) and this partially explained the above association. These estimates for cognitive decline were relatively small and may lack clinical relevance. CONCLUSION: Low cognitive ability increases the risk of benzodiazepine use in adulthood and cognitive decline is more pronounced in those with the highest benzodiazepine use compared with never-use, but the difference lacks clinical significance.

Changes in S100 calcium-binding protein ß (S100ß) and cognitive function from pre- to post-chemotherapy among women with breast cancer.

Many patients with cancer experience cancer-related cognitive decline (CRCD). Previous studies have shown that elevated S100ß, a calcium-binding protein commonly found in glial cells, can exhibit neurotoxic effects, including disruption of the blood-brain barrier (BBB). We studied changes in S100ß levels in patients with breast cancer receiving chemotherapy, and the relationship to changes in cognitive function. A total of 505 women with breast cancer (mean (sd) age; 53.4 (53.6)) and 336 age-matched controls without cancer (52.8 (10.3)) were included from a nationwide study as part of the National Cancer Institute Community Oncology Research Program (NCORP). Both groups provided blood samples and completed neurocognitive assessments within 7 days before the patients with breast cancer received their first chemotherapy dose (pre-chemotherapy; T1) and within 1 month of their last chemotherapy administration (post-chemotherapy; T2). Utilizing a linear mixed model, multivariate linear regressions, and Spearman rank correlations (rs), we investigated longitudinal changes in serum S100ß concentrations and their relationships to changes in neurocognitive outcomes over time. We observed an increase in S100ß for patients with breast cancer (p = 0.002), but not for controls without cancer over time (p = 0.683). Additionally, we identified subtle relationships between increases in serum S100ß and worsening in cognitive performance on the Backward Counting test (rs = 0.11, p = 0.041) and self-reported FACT-Cog Perceived Cognitive Abilities (rs = -0.10, p = 0.025). Regression analyses adjusted for age, race, body-mass index (BMI), education, menopausal status, anxiety, and depression revealed a trend remained for the relationship of S100ß with Backward Counting. In conclusion, we found that patients with breast cancer experience a significant increase in concentration of serum S100ß over the course of chemotherapy. This increase is correlated with worsening in some neurocognitive outcomes from pre-to post-chemotherapy, with trending results remaining following adjustment for covariates.

Minocycline prevents early age-related cognitive decline in a mouse model of intellectual disability caused by ZBTB18/RP58 haploinsufficiency.

Haploinsufficiency of the transcriptional repressor ZBTB18/RP58 is associated with intellectual disability. However, the mechanisms causing this disability are unknown, and preventative measures and treatments are not available. Here, we assessed multiple behaviors in Zbtb18/Rp58 heterozygous-knockout mice, and examined local field potentials, DNA fragmentation, mitochondrial morphology, and performed histochemical and transcriptome analyses in the hippocampus to evaluate chronic inflammation. In wild-type mice, object location memory was present at a similar level at 2 and 4-5 months of age, and became impaired at 12-18 months. In contrast, Zbtb18/Rp58 heterozygous-knockout mice displayed early onset impairments in object location memory by 4-5 months of age. These mice also exhibited earlier accumulation of DNA and mitochondrial damage, and activated microglia in the dentate gyrus, which are associated with defective DNA repair. Notably, chronic minocycline therapy, which has neuroprotective and anti-inflammatory effects, attenuated age-related phenotypes, including accumulation of DNA damage, increased microglial activation, and impairment of object location memory. Our results suggest that Zbtb18/Rp58 activity is required for DNA repair and its reduction results in DNA and mitochondrial damage, increased activation of microglia, and inflammation, leading to accelerated declines in cognitive functions. Minocycline has potential as a therapeutic agent for the treatment of ZBTB18/RP58 haploinsufficiency-associated cognitive dysfunction.

Impact of Androgen Deprivation Therapy on Cognitive Function of Elderly Men With Prostate Cancer.

Background Prostate cancer affects millions of men worldwide. Androgen deprivation therapy is the most prescribed medication for elderly men with prostatic cancer to slow and suppress the disease progression. Androgen deprivation therapy works on decreasing testosterone levels, and that can cause multiple side effects, including potential cognitive affection in the form of accelerating cognitive aging and potentially increasing the risk of dementia. This study is aimed at evaluating the impact of androgen deprivation therapy on the cognitive function of elderly men recently diagnosed with prostate cancer. Methods The current research is a prospective cohort study conducted on 85 elderly patients recently diagnosed with prostate cancer who are about to start androgen deprivation therapy within two weeks of the diagnosis. These patients were recruited from the oncology and geriatrics outpatient clinics of Ain Shams University hospitals and were followed up on androgen deprivation therapy for at least six months. Cognitive and depression assessments were done using the Montreal Cognitive Assessment Test and Montreal Cognitive Assessment Test-Basic (according to their education) and the Patient Health Questionnaire-9. The cases were assessed at the start, after two months, and after six months of androgen deprivation therapy use. Cognitively impaired or depressed patients were excluded at the beginning of the study. Results This study showed that 49 out of 85 (57.6%) of the studied participants had a lower Montreal cognitive assessment test score average after six months, indicating mild cognitive impairment. Cognitive domains such as visuospatial, language, and attention were affected. About one-third of the participants were diagnosed with depression after six months of the androgen deprivation therapy. All the depressed participants had cognitive impairment. Conclusion The use of androgen deprivation therapy carries the risk of cognitive decline and regression of some of the cognitive domains such as language, visuospatial, attention, and depression in the elderly with recently diagnosed prostate cancer who received ADT for six months. Conversely, depression could not be linked to cognitive decline. Further research should continue exploring the relationship between cognitive decline and ADT and seek strategies to mitigate these effects, ensuring comprehensive patient care targeting cognitive and psychological well-being.

Association between mobility limitations and cognitive decline in community-dwelling older adults: the English Longitudinal Study of Ageing.

BACKGROUND AND OBJECTIVES: Mobility limitations has been linked to cognition. However, little is known about the relationship between mobility decline and cognitive decline. This study investigated the effect of mobility limitations and decline on cognitive decline in a population-based cohort of older adults. RESULT DESIGN AND METHODS: A population-based cohort of 9695 cognitively intact participants (mean age = 65.4 years, standard deviation [SD] = 10.4) was assessed. Mobility limitation scores ranging from 0-10 were assessed at baseline (wave 4) by using self-reporting difficulty in a set of 10 activities, and a higher score indicated worse mobility. A subset of 9250 participants underwent two mobility assessments at waves 3 and 4, and were categorized into normal mobility or mobility decline (defined as wave 4 - wave 3 > 1 SD of wave 3). Linear mixed models were used to assess the longitudinal contribution of mobility limitations and decline to cognitive decline. RESULTS: During a median follow-up period of 9.4 years (SD 1.8), the participants in the highest quartile of mobility scores displayed an accelerated cognitive decline (-0.191 SD/year, 95% CI = -0.223, -0.159) compared with those in the lowest quartile. Notably, individuals experiencing mobility decline exhibited a marked cognitive decline (-0.179 SD/year, 95% CI = -0.220, -0.139), potentially influenced by factors such as physical activity and depression. DISCUSSION AND IMPLICATIONS: Mobility limitations and decline significantly correlate with cognitive decline in older adults, highlighting that mobility-focused interventions in healthcare strategies to preserve cognition.

Latent classes of sleep problems and subjective cognitive decline among middle-aged and older adults in the United States.

OBJECTIVE: Previous studies have linked sleep problems to subjective cognitive decline (SCD) using a variable-centered approach (e.g., adding sleep symptoms to form a score); however, sleep problems may cluster differently between individuals. Thus, employing a person-centered approach, we aimed to: 1) identify profiles of self-reported sleep problems among U.S. middle-aged and older adults; 2) examine the cross-sectional association between these classes and SCD. METHODS: We studied 33,922 adults aged 45+ years from the 2017 U.S. Behavioral Risk Factor Surveillance System (BRFSS) with data on sleep problems, including short or long sleep duration, trouble falling or staying asleep, unintentionally falling asleep, snoring loudly, and observed apneas. Latent class analysis classified participants based on their responses to sleep items. We then used a subsample from Oregon, the only state that administered both sleep and SCD modules (n = 2,747), to examine the association between class membership and SCD using logistic regression, adjusting for sociodemographic and health-related characteristics. RESULTS: We identified and labeled four classes: "Healthy Sleep" (48.0 %); "Primarily Apnea" (25.8 %); "Primarily Insomnia" (17.6 %); and "Comorbid Insomnia and Sleep Apnea (COMISA)" (8.6 %). In adjusted models, individuals in the "COMISA" class had almost twice the odds of SCD, compared to those in the "Healthy Sleep" class (OR=1.91, 95 % CI =1.15-3.15). CONCLUSIONS: Compared to U.S. middle-aged and older adults with healthy sleep, those with COMISA were significantly more likely to report SCD, which is a risk factor for dementia. Studies are needed investigating whether sleep interventions delay cognitive decline in these individuals.