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PubMed2026

Prognostic Value of Blood-Based P-Tau217 Levels for Progression to Cognitive Impairment.

IMPORTANCE: Blood-based biomarkers for Alzheimer disease, particularly plasma phosphorylated tau 217 (p-tau217), accurately reflect early Alzheimer disease brain pathology in cognitively unimpaired individuals, but estimates of absolute risk of progression to cognitive impairment across multiple cohorts are needed. OBJECTIVE: To estimate absolute risk of progression to cognitive impairment and rates of cognitive decline based on plasma p-tau217 across cognitively unimpaired older adults. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal cohort study using harmonized data from 2684 cognitively unimpaired older adults (defined within cohort) across 6 observational and clinical trial cohorts based in North America, Japan, and Australia. The earliest enrollment was in 2004, with most recent follow-up in 2025. EXPOSURE: Baseline plasma p-tau217. MAIN OUTCOMES AND MEASURES: The primary outcome was time to progression to cognitive impairment (mild cognitive impairment, dementia, or 2 consecutive global Clinical Dementia Rating scores ≥0.5). The secondary outcome was longitudinal change on the latent Preclinical Alzheimer Cognitive Composite (PACC; higher values indicate better performance). RESULTS: Among the 2684 participants (median [IQR] age, 69.6 [66.2-74.2] years; 1697 [63%] female), there were 478 events of progression to cognitive impairment over a median follow-up of 5.4 years (maximum follow-up of 13.5 years). Each 1-SD increase in baseline p-tau217 level was associated with an increased risk of progression to cognitive impairment (hazard ratio, 1.38 [95% CI, 1.30-1.46]), and the association remained significant after adjustment, including β-amyloid positron emission tomography scan Centiloids (hazard ratio, 1.32 [95% CI, 1.24-1.41]). Participants with high (1.1-2.4 SD) and very high (>2.5 SD) baseline p-tau217 had 24% (95% CI, 20%-28%) and 38% (95% CI, 33%-43%) absolute risk of progression over 5 years, respectively, and risk was markedly higher over 10 years, although longer-term estimates were constrained by limited data. Elevated p-tau217 was also associated with faster cognitive decline based on change in latent PACC score. Among the overall sample, baseline latent PACC scores ranged from -0.8 to 2.7. The 5-year annualized decline for the very high p-tau217 group was -0.07 latent PACC units/y (95% CI, -0.10 to -0.05), relative to 0.03 units/y (95% CI, 0.02-0.04) in the low p-tau217 group. CONCLUSIONS AND RELEVANCE: In a pooled sample of multiple selected cohorts of cognitively unimpaired older adults, higher plasma p-tau217 levels were consistently associated with increased risk of clinical progression and accelerated cognitive decline. By providing time-specific absolute risk estimates, these findings support the potential of p-tau217 for prognostic model development, with direct implications for future trial design. Further validation in unselected populations is needed to inform individual prognosis and clinical decision-making in cognitively unimpaired individuals.

Aged↗

PubMed2026

Cognitive-metabolic relationship in temporal lobe epilepsy: A systematic review.

OBJECTIVE: To summarize the current literature on neurometabolic dysfunction identified through brain imaging and its cognitive correlates in temporal lobe epilepsy (TLE). BACKGROUND: Cognitive decline contributes to chronic disability in TLE. The pathophysiology of cognitive decline in TLE is poorly understood, limiting therapeutic advances. Characterizing metabolic changes in patients with TLE and cognitive impairment may identify biomarkers and inform new treatment strategies. DESIGN/METHODS: We conducted a systematic review of five major databases, gathering studies published through December 2024, in accordance with PRISMA guidelines. We included all observational studies describing associations between metabolic imaging findings and cognitive measures in TLE. RESULTS: Of 1449 reports, 38 met the inclusion criteria, encompassing 1161 patients with TLE aged 5-66 years. Twenty-two studies applied fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to assess interictal brain glucose metabolism. Two studies utilized PET with other tracers to assess more specific metabolic aspects. Fourteen studies used proton magnetic resonance spectroscopy (1H-MRS) to quantify local concentrations of brain metabolites. Impairment of verbal memory was consistently associated with left temporal lobe metabolite changes. Non-memory cognitive impairments correlated with changes in glucose metabolism, N-acetylaspartate, and gamma-aminobutyrate in both temporal and extratemporal areas. CONCLUSION: 18F-FDG PET remains the most widely used imaging modality to assess cognitive-metabolic correlates in TLE, while other PET tracers and 1H-MRS are potentially underexplored. Verbal memory impairment correlates robustly with left temporal dysmetabolism. Cognitive impairment in TLE is multifaceted and correlates with measurable changes in metabolism in both temporal and extratemporal regions. While our synthesis was restricted by some methodological limitations, these neurometabolic signatures may hold promise as potential biomarkers for identifying risk of cognitive decline and highlight avenues for future research.

Humans↗

PubMed2026

TACR3 variant confers resilience to aging and Alzheimer's disease.

BACKGROUND: While genetic factors strongly influence brain aging trajectories, variants conferring cognitive resilience remain poorly characterized. The neurokinin-3 receptor (NK3-R), encoded by Tachykinin Receptor 3 (TACR3), modulates cholinergic signaling in memory circuits vulnerable to aging. Previous studies linked the non-WT expression of the TACR3 variant rs2765 with cognitive decline and reduced volume of the hippocampus and basal forebrain, but systematic replication and mechanistic validation were lacking. METHODS: We investigated rs2765 in the preregistered AgeGain cohort of cognitively healthy older adults (n=188) with independent validation in the ADNI cohort (n=809) which includes persons with and without Alzheimer's Disease (AD) that show healthy cognition, mild cognitive impairment or dementia. Analyses integrated structural neuroimaging, longitudinal cognitive assessments, epigenetic aging (PhenoAge), genome-wide methylation profiling, and mechanistic validation through luciferase assays and cross-species protein expression studies. RESULTS: The infrequent protective rs2765 WT variant, found in 12.8% of Europeans, conferred 49% slower cognitive decline (p = 0.002) for amyloid-positive individuals of the ADNI cohort and 3.7 years younger epigenetic age (p = 0.013, 95% CI: 0.79-6.67 years) in the cognitively healthy AgeGain cohort. WT carriers showed larger hippocampal and basal forebrain volumes across cohorts, with Allen Brain Atlas integration revealing these outcomes to occur exclusively in regions where TACR3 expression positively correlated with gray matter volume. Mechanistically, the non-WT variant ameliorated RBMX-mediated post-transcriptional regulation, reducing NK3-R protein expression by 25-40% in vitro and ex vivo murine brain slice models. Senescence-accelerated mice exhibited reduced endogenous NK3-R expression, phenocopying the predicted functional consequences of the variant. In AgeGain participants, genome-wide methylation profiling identified 2,313 differentially methylated CpGs affecting 228 pathways spanning glutamatergic signaling, acetylcholine receptor pathways, chromatin remodeling, and angiogenesis, suggesting coordinated molecular reprogramming from synaptic function to systemic aging. CONCLUSIONS: rs2765 WT confers resilience to age- and AD-related cognitive decline through RBMX-dependent regulation of NK3-R expression, with effects of remarkable size cascading from memory to systemic aging. rs2765 genotyping could stratify individuals for NK3-R modulator therapy (e.g., fezolinetant or senktides) and identify those maintaining function despite pathological burden, complementing APOE-based risk assessment in precision geromedicine.

Journal Article↗

PubMed2025

Association Between Ratio of Triglycerides to HDL-C and Cognitive Impairment: A Longitudinal Population-Based Analysis and Mendelian Randomization Study.

OBJECTIVES: This study aimed to explore the longitudinal association between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and cognitive impairment in older adults and further assess potential causality using Mendelian randomization (MR). DESIGN: Longitudinal population-based analysis combined with two-sample MR. Data from Waves 6-8 (2015-2019) of the Survey of Health, Ageing, and Retirement in Europe (SHARE) were analyzed using hierarchical regression models and mixed linear effects models. MR utilized genome-wide association studies (GWAS) summary data. PARTICIPANTS: 11,444 adults aged ≥60 years from SHARE Wave 6, with longitudinal follow-up in Waves 7 (N = 2,775) and 8 (N = 5,469). MEASUREMENTS: TG/HDL-C ratio, cognitive function (orientation, immediate/delayed recall, verbal fluency, numeracy), and cognitive impairment (defined as scores >1.5 SD below age-group mean). Covariates included socio-demographics, health behaviors, comorbidities, and national-level factors. MR employed genetic variants associated with TG/HDL-C as instrumental variables. RESULTS: Higher TG/HDL-C ratios were negatively associated with total cognitive scores (β = -0.115, χ² = 15.44, df = 1, p < 0.001), immediate recall (β = -0.029, χ² = 12.34, df = 1, p < 0.001), delayed recall (β = -0.028, χ² = 7.33, df = 1, p < 0.001), verbal fluency (β = -0.038, χ² = 11.53, df = 1, p < 0.001), and numeracy (β = -0.019, χ² = 4.55, df = 1, p < 0.05) in fully adjusted models. Longitudinal analysis revealed increased cognitive impairment risk in the highest TG/HDL-C quartile (OR=1.43, 95% CI:1.01-2.03, χ² = 9.24, df = 1) over 4 years. MR supported a causal link between elevated TG/HDL-C and cognitive decline. CONCLUSIONS: Elevated TG/HDL-C ratios are longitudinally associated with cognitive decline in older adults. Managing lipid metabolism may mitigate cognitive impairment, highlighting the importance of TG/HDL-C as a modifiable risk factor in aging populations.

Humans↗

PubMed1977

Do cognitive abilities decline with age?

Explore the source record for details and available documents.

Aged↗

PubMed2026

Social support and cognitive function in postmenopausal women.

OBJECTIVE: An active social lifestyle may protect against cognitive decline in older adults, but few studies have examined specific social support dimensions in relation to specific cognitive domains. This study examines associations between social support dimensions and cognitive function in older women. METHODS: The Early versus Late Intervention Trial with Estradiol (ELITE) was a randomized, double-blinded, placebo-controlled trial of oral 17β-estradiol versus placebo in postmenopausal women, designed primarily to evaluate the timing hypothesis on atherosclerosis progression and cognitive decline; the present analysis is a secondary, hypothesis-generating examination of the psychosocial substudy data (2009-2012). A total of 448 women completed psychosocial assessments every 6 months. Cognitive function was assessed at baseline, 2.5, and 5 years using composite scores for executive function, verbal memory, visual memory, and global cognition derived from 14 standardized tests. Perceived social support was assessed using the Medical Outcomes Study-Social Support Survey (MOS-SSS; 0-100 scale). Paired cognitive-psychosocial assessments were analyzed using linear mixed-effects models adjusted for age, marital status, blood pressure medication, BMI, education, income, race, and randomized treatment (hormone therapy or placebo). RESULTS: A total of 298 women (mean age 60.3 y) provided 322 paired visits. Positive associations were observed between instrumental social support and visual memory (β(SE)=0.0044(0.0022), 95% CI: -0.00002 to 0.0088, P=0.051) and between positive social interaction and global cognition (β(SE)=0.0092(0.0046), 95% CI: 0.0001-0.0182, P=0.047). In age-stratified analyses, the positive social interaction-global cognition association was significant among women <65 years (P=0.042) but not women ≥65 years (P=0.34). No association survived false discovery rate (FDR) correction for multiple comparisons. CONCLUSIONS: In this sample of healthy middle- to older-aged women, no association between specific dimensions of social support and cognitive domains was statistically significant after correction for multiple comparisons. These hypothesis-generating findings suggest any association is modest at best and warrant confirmation in studies designed specifically for this question.

Cognitive function↗

PubMed2026

Longitudinal Neurocognitive Changes for Patients With Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplantation: A Systematic Review With Structured Narrative Synthesis.

OBJECTIVES: Neurocognitive changes in hematological malignancies (HM) and as a sequela of hematopoietic stem cell transplantation (HSCT) remain under-recognized. These changes may substantially affect patients' quality of life. Therefore, this review systematically evaluated longitudinal neurocognitive changes in patients with HM undergoing HSCT. METHODS: Following PRISMA guidelines, PubMed, Scopus, and CINAHL were searched on October 30, 2025. Longitudinal studies assessing neurocognitive changes in patients with HM undergoing HSCT, with or without healthy controls, were included. Risk of bias was assessed using an adapted National Institutes of Health quality assessment tool for before-after studies. Effect sizes with 95% confidence intervals were calculated to quantify changes in neurocognitive performance. RESULTS: Nine of 2012 studies met the inclusion criteria, with overall moderate study quality. Improvements may occur post-HSCT; however, allogeneic HSCT and myeloablative conditioning were main risk factors identified for persistent cognitive decline. In line with white matter damage, executive function and attention/processing speed impairments likely represent core deficits, which may affect other cognitive impairments. Post-HSCT changes depend on task characteristics, cognitive load, and conditioning intensity. CONCLUSIONS: Future research should emphasize regular neurocognitive assessment to guide cognitive rehabilitation, implement pre-transplant cognitive rehabilitation strategies to mitigate post-HSCT cognitive decline, and enhance treatment outcomes.

Humans↗

PubMed2025

The Effect of APOE ε4 Allele on Dynamic Local Spontaneous Brain Activity and Functional Integration in Alzheimer's Disease.

The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for sporadic Alzheimer's disease (AD), yet its mechanisms in AD pathology and cognitive decline remain unclear. Using a sliding-time window approach to directly quantify the instantaneous fluctuations of various local metrics based on continuous time series and calculate voxel-wise concordance of these metrics, we explored the impact of APOE ε4 on dynamic local brain activity and functional integration in AD, and its interrelations with plasma biomarkers and cognition. Results showed that APOE ε4 widely affected dALFF, dReHo, dGSCorr, and voxel-wise concordance. For AD patients, APOE ε4 carriers uniquely exhibited correlations between dALFF in the right angular gyrus/supramarginal gyrus and MoCA scores and orientation function, and between voxel-wise concordance in the right caudate nucleus (CAU) and general cognition, attention, language function, orientation function, plasma Aβ42. Critically, APOE ε4-related altered voxel-wise concordance in the right CAU mediated the relationship between plasma Aβ and language cognition in AD. Moreover, the combined model incorporating dynamic metrics, plasma AD biomarkers, and demographic data effectively distinguished AD from NC (AUC = 0.94, sensitivity = 87.69%, specificity = 86.84%). In conclusion, the APOE ε4 allele might play a pivotal role in modulating brain dynamic functional activities in AD, which may contribute to the association between Aβ pathology and cognitive decline. Our findings may provide imaging markers and targets for the diagnosis and treatment of AD.

Humans↗

PubMed2025

Protective Effects of Genetic Proxies of Cognitive Reserve in Parkinson's Disease: A Longitudinal Multi-Cohort Study.

BACKGROUND: Resilience factors are crucial in the progression of neurodegenerative diseases. However, it remains unclear whether a genetic predisposition to cognitive reserve influences clinical heterogeneity in the prognosis of Parkinson's disease (PD). OBJECTIVES: The aim is to evaluate the utility of polygenic scores (PGSs) for cognitive reserve proxies, including intelligence (INT), educational attainment (EA), and occupational attainment (OA), in predicting the clinical progression of PD. METHODS: Genetic and clinical data for progression of PD (progression to Hoehn and Yahr stage ≥3, progression to a Montreal Cognitive Assessment score ≤24, and occurrence of psychosis) were obtained from the Accelerating Medicine Partnership Parkinson's Disease database. We conducted multivariate Cox regression analysis, adjusting for relevant covariates, including years of education, variants in APOE, GBA1, LRRK2, and other cognitive reserve-related PGSs. RESULTS: All cognitive reserve-related PGSs significantly reduced the risk of cognitive decline, and EA-PGS (hazard ratio [HR], 0.550; 95% confidence interval [CI], 0.447-0.676; P < 0.001) remained significant after controlling for INT-PGS and OA-PGS. EA-PGS (HR, 0.805; 95% CI, 0.672-0.964; P = 0.019) was significantly associated with better motor prognosis after controlling for other PGSs. OA-PGS was linked to a decreased risk of developing psychosis in PD and remained significant after adjusting for others (HR, 0.784; 95% CI, 0.631-0.975; P = 0.029). CONCLUSIONS: Genetic proxies of cognitive reserve are associated with a reduced risk of cognitive decline, motor progression, and development of psychosis in PD. These findings may enhance our understanding of individual differences in resilience in progression of PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Humans↗

PubMed2025

Patient stratification by genetic risk in Alzheimer's disease is only effective in the presence of phenotypic heterogeneity.

Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science. In four cohorts (n = 7241), we performed genome-wide association studies (GWAS) and Mendelian randomization (MR) to discover novel targets associated with progression and assess causal relationships. We tested opportunities for patient stratification by deriving polygenic risk scores (PRS) for AD risk and severity and tested the value of these scores in predicting progression. Genome-wide association studies identified no loci associated with progression at genome-wide significance (α = 5×10-8); MR analyses provided no significant evidence of an association between cognitive decline in AD patients and protein levels in brain, cerebrospinal fluid (CSF), and plasma. Polygenic risk scores for AD risk did not reliably stratify fast from slow progressors; however, a deeper investigation found that APOE ε4 status predicts amyloid-β and tau positive versus negative patients (odds ratio for an additional APOE ε4 allele = 5.78 [95% confidence interval: 3.76-8.89], P<0.001) when restricting to a subset of patients with available CSF biomarker data. These results provided no evidence for large-effect, common-variant loci involved in the rate of memory decline, suggesting that patient stratification based on common genetic risk factors for progression may have limited utility. Where clinically relevant biomarkers suggest diagnostic heterogeneity, there is evidence that a priori identified genetic risk factors may have value in patient stratification. Mendelian randomization was less tractable due to the lack of large-effect loci, and future analyses with increased samples sizes are needed to replicate and validate our results.

Alzheimer Disease↗

PubMed2026

Loss of ovarian function and estrogen therapy remodel the brain's synaptic and metabolic proteome.

Menopause is linked to cognitive decline and reduced brain metabolism, whereas estrogen (E2) therapy has been shown to mitigate these effects. Understanding the molecular mechanisms by which ovarian hormones and E2 influence neuroprotection is essential for developing strategies to maintain brain health in women. In this study, we examined how the loss of ovarian hormones, with or without E2 treatment, affects the brain proteome and mitochondrial energy production in aged female C57BL/6J mice (36-40 wk). The mice underwent sham or ovariectomy (OVX) surgery and were fed a high-fat diet for 10 wk; 6 wk after surgery, OVX mice received either sesame oil or E2 treatment for 4 wk. Proteomic analysis of brain homogenates revealed 4,992 proteins regulated by E2, with pathway analysis showing increased signaling proteins related to synaptogenesis. OVX reduced proteins involved in synaptic function, branched-chain amino acid and ketone metabolism, the tricarboxylic acid cycle, and oxidative phosphorylation (Complexes I, IV, and V), whereas E2 restored protein expression within these pathways. Despite alterations in OxPhos proteins, basal and state 3 mitochondrial respiration remained unchanged, although notable impairments in Complex IV enzymatic activity were apparent in OVX, which were partially reversed by E2 treatment. Overall, these results indicate that E2 supports brain health by maintaining proteins crucial for synaptic integrity and metabolism, while partially offsetting the functional decline in mitochondrial bioenergetics associated with menopause.NEW & NOTEWORTHY The menopausal transition, marked by declining estrogen levels, alters cognition, neuroplasticity, and brain metabolism. Although hormone therapy benefits cognition, its molecular effects on the brain remain unclear. Using whole-brain proteomics in aged ovariectomized (OVX) mice with or without estrogen treatment, we found that OVX reduced proteins linked to synaptogenesis and mitochondrial metabolism. Estrogen reversed these declines, restoring pathways supporting neuronal signaling and energy balance, identifying estrogen-regulated proteins critical for maintaining brain health during menopause.

Animals↗

PubMed2025

Phenotypic and Genetic Associations Between Cardiovascular Disease Subtypes and Alzheimer's Disease.

BACKGROUND: Cardiovascular disease (CVD) and Alzheimer's disease (AD) are major public health concerns that share overlapping risk factors and potential mechanistic pathways. While vascular contributions to cognitive decline are well-documented, the specific relationships between AD and different CVD subtypes remain poorly understood. METHODS: We examined associations between AD and 11 CVD subtypes using logistic regression models in two large biobanks: the UK Biobank (n = 502,133) and the All of Us Research Program (n = 287,011). Models were adjusted for demographic, lifestyle, and clinical covariates. We also explored genetic overlap between AD and CVD traits through colocalization of significant single nucleotide polymorphisms (SNPs) (p < 5×10-8) using genome-wide association study (GWAS) data. RESULTS: Most CVD subtypes were significantly associated with AD in both cohorts. Hypotension had the strongest and most consistent association, followed by hypertension and cerebral infarction. Acute myocardial infarction was the only subtype not significantly linked to AD. Genetic analyses revealed shared loci between AD and CVD-related traits, particularly in regions near APOE, MAPT, and genes influencing myocardial structure and vascular function. CONCLUSIONS: This study identifies subtype-specific CVD associations with AD across two diverse cohorts and highlights shared genetic architecture underlying heart-brain interactions. These findings underscore the importance of vascular health in AD risk and suggest that certain CVD subtypes, especially hypotension, may play underrecognized roles in cognitive decline.

Alzheimer’s disease↗

PubMed2024

Polygenic burden and its association with baseline cognitive function and postoperative cognitive outcome in temporal lobe epilepsy.

OBJECTIVE: Demographic and disease factors are associated with cognitive deficits and postoperative cognitive declines in adults with pharmacoresistant temporal lobe epilepsy (TLE), but the role of genetic factors in cognition in TLE is not well understood. Polygenic scores (PGS) for neurological and neuropsychiatric disorders and IQ have been associated with cognition in patient and healthy populations. In this exploratory study, we examined the relationship between PGS for Alzheimer's disease (AD), depression, and IQ and cognitive outcomes in adults with TLE. METHODS: 202 adults with pharmacoresistant TLE had genotyping and completed neuropsychological evaluations as part of a presurgical work-up. A subset (n = 116) underwent temporal lobe resection and returned for postoperative cognitive testing. Logistic regression was used to determine if PGS for AD, depression, and IQ predicted baseline domain-specific cognitive function and cognitive phenotypes as well as postoperative language and memory decline. RESULTS: No significant findings survived correction for multiple comparisons. Prior to correction, higher PGS for AD and depression (i.e., increased genetic risk for the disorder), but lower PGS for IQ (i.e., decreased genetic likelihood of high IQ) appeared possibly associated with baseline cognitive impairment in TLE. In comparison, higher PGS for AD and IQ appeared as possible risk factors for cognitive decline following temporal lobectomy, while the possible relationship between PGS for depression and post-operative cognitive outcome was mixed. SIGNIFICANCE: We did not observe any relationships of large effect between PGS and cognitive function or postsurgical outcome; however, results highlight several promising trends in the data that warrant future investigation in larger samples better powered to detect small genetic effects.

Adult↗

PubMed2026

Effectiveness of psychosocial and lifestyle interventions in promoting behaviour change and improving cognitive outcomes in older people with memory concerns: A systematic review.

BACKGROUND: Older adults with mild cognitive impairment or subjective cognitive decline have a greater dementia risk, particularly those from minority ethnic and socioeconomically disadvantaged backgrounds. Psychosocial and lifestyle interventions targeting modifiable risk factors offer hope for reducing risk, yet behavioural mechanisms remain unclear. This systematic review examines these mechanisms and associated outcomes. METHOD: We searched PubMed, Embase (Ovid), PsycINFO (Ovid), Web of Science, and Scopus for randomised control trials testing interventions that aimed to improve lifestyle and cognition in older adults with memory concerns. We explored behavioural mechanisms using the COM-B model and synthesised intervention effectiveness, overall and within underserved groups. We prioritised lower risk of bias studies. RESULTS: 26 studies described 23 randomised controlled trials (14 multidomain, 9 single domain interventions). Certainty of evidence that behaviour change was associated with cognition was low. Moderate-certainty evidence indicated that interventions providing a socially supportive environment and combining nutritional education and counselling for 6 + months improved diet. Physical activity improved primarily in interventions incorporating education, structured training, and enablement strategies (e.g., tailored programmes, providing tools). Interventions simultaneously targeting capability, opportunity and motivation showed greater overall effectiveness. Few studies recorded ethnicity (13%) or sociodemographic status (9%), and none explored their impact. CONCLUSIONS: Non-pharmacological interventions can help this population improve their lifestyles if they feel capable, equipped and motivated, highlighting the value of careful design and implementation. There is scarce evidence on how these interventions work for underserved populations. Future research should explore this to inform tailored interventions and develop equitable dementia prevention strategies.

Humans↗

PubMed1992

A new systematic method of measurement and diagnosis of "mild cognitive impairment" and dementia according to ICD-10 and DSM-III-R criteria.

Normative data were collected in a study population of 150 randomly selected elderly subjects. Using the SIDAM (Structured Interview for the Diagnosis of Dementia of the Alzheimer Type, multi-infarct dementia, and dementias of other etiology according to DSM-III-R and ICD-10), both the dimensional and the categorical aspects of dementia and "mild cognitive impairment" are considered. With the SIDAM score (SISCO) [range 0 (minimum)-55 (maximum, no cognitive impairment)] and the SIDAM Mini-Mental State Examination (MMSE) (range 0-30), appropriate cutoffs for the category of DSM-III-R and ICD-10 dementia and "mild cognitive impairment" were defined. MMSE scores of 0-22 were found to be indicative of DSM-III-R and ICD-10 dementia. For "mild cognitive impairment," MMSE scores ranged from 23-27 according to a DSM-III-R definition (ICD-10: 23-28). An MMSE score of 22 or less was found to differentiate between DSM-III-R/ICD-10 dementia and "mild cognitive impairment," with a specificity of 92% (ICD-10: 95.6) and a sensitivity of 96% (ICD-10: 96%). With the SIDAM-based DSM-III-R/ICD-10 diagnoses of dementia as the criterion, the SISCO was 97.3% specific (ICD-10: 99%) and 94% sensitive (ICD-10: 94%) in detecting dementia. A SISCO of 0-33 was highly indicative of DSM-III-R and ICD-10 dementia. For "mild cognitive impairment," a SISCO between 34-47 (ICD-10: 34-51) was found. The SISCO covers a broader range of cognitive functions than the MMSE and is more useful in detecting even very mild cognitive decline. Furthermore, the newly defined category of "mild cognitive impairment" could be validated successfully by means of GDS Stages 2-3 and CDR Stage 0.5. These findings confirm the value of the SIDAM as a short diagnostic instrument for measurement and diagnosis of dementia and "mild cognitive impairment."

Aged↗

PubMed2026

Investigating the relationship between Toll-like receptor activity, low-grade inflammation, cognitive deficits, and antipsychotic drug dose in schizophrenia patients: a moderation analysis.

BACKGROUND: Schizophrenia (SZ) is a debilitating psychiatric disorder where patients experience cognitive decline. Antipsychotic drugs alleviate positive symptoms but do not improve cognitive performance. We previously demonstrated that Toll-like receptors (TLRs), involved in cytokine production, can predict cognitive deficits in SZ patients. In this study, we aim to investigate the potential moderating effects of antipsychotic drugs on the associations between cytokines, TLRs, and cognition. METHODS: In total, 280 participants (201 controls and 79 cases of SZ) were recruited in Ireland. Venous blood from the participants was stimulated with TLR ligands. Levels of cytokines were measured from plasma and post-blood stimulation. The participants were administered a battery of cognitive tasks using the Cambridge Neuropsychological Test Automated Battery and Wechsler Adult Intelligence Scale-IIIR. Olanzapine equivalents were calculated using the defined daily dose method. RESULTS: The results indicate that antipsychotic drug dose does not predict TLR activity or cognition, indicating that antipsychotic drug dose does not have a direct effect on cognition or TLR activity. However, the relationship between TLR4 activity and visual learning and memory is moderated by the antipsychotic drug dose (B = -0.065; p < 0.001), where increasing doses have a decreasing impact on their relationship. CONCLUSIONS: Our data indicate that the dose of antipsychotic drugs alone cannot predict changes in cognitive performance and TLR4-activity. It also suggests that antipsychotic drug doses significantly affect TLR activity and its relationship with cognition. These effects are more pronounced on some domains than others. These findings open up new avenues for understanding the complex interplay between antipsychotic drugs, TLRs, and cognitive deficits in SZ.

Humans↗

PubMed2025

Impact of Chewing Behavior Change on Cognition and Cerebral Hemodynamics.

BACKGROUND: Impaired chewing ability is a recognized risk factor for cognitive decline in older adults, potentially due to reduced neural stimulation in cognition-related brain regions. While short-term studies have demonstrated transient increases in neural activity from chewing, the sustained cognitive and neurophysiological effects of encouraging thorough chewing habits in daily life remain unclear. OBJECTIVE: This randomized controlled trial investigated whether promoting thorough chewing during meals could improve cognitive function and cerebral hemodynamics in older adults. METHODS: Fifty participants aged 65 y or older were randomly assigned to either a 1-mo intervention group, which used a wearable device to monitor and increase chewing strokes during meals, or a control group that maintained usual chewing habits. Chewing behavior, cognitive performance (including memory and executive function via the color Stroop test), and cerebral hemodynamics in the dorsolateral prefrontal cortex (DLPFC) were measured at baseline and after 1 mo. Statistical analyses included t tests, chi-square tests, 2-way analysis of variance with post hoc tests, Pearson correlations, and generalized linear models to evaluate group differences and associations between chewing and cognitive outcomes. RESULTS: Significant time-by-group interactions were observed for memory, F(1, 48) = 6.24, P = 0.043, and hemodynamic responses in the left DLPFC, F(1, 48) = 6.19, P = 0.013. The intervention group showed increased chewing frequency (P = 0.017), improved memory performance, and reduced left DLPFC responses compared with controls. Chewing frequency was positively correlated with Stroop test scores (r = 0.53, P = 0.010) and negatively with hemodynamic changes in the left DLPFC (r = -0.30, P = 0.040). Although improvements in other cognitive outcomes and hemodynamic measures favored the intervention group, these differences did not reach statistical significance. CONCLUSIONS: Promoting intentional chewing habits for 1 mo may enhance memory-related cognitive performance and neural efficiency in the DLPFC during working memory tasks in older adults. This nonpharmacologic, low-burden strategy warrants further research with longer interventions to support cognitive health and dementia prevention. TRIAL REGISTRATION ID: UMIN000044280Knowledge Transfer Statement:This study demonstrates that promoting thorough chewing habits in older adults can improve memory and enhance neural efficiency in the brain. Encouraging intentional mastication is a simple, nonpharmacologic approach that may help maintain cognitive health and prevent dementia, providing a practical strategy for clinicians and policymakers to support healthy aging.

Humans↗

PubMed2026

Association between Kidney Tubular Secretory Clearance with Cognitive Function among Adults with CKD in the Systolic Blood Pressure Intervention Trial.

BACKGROUND: Persons with CKD are disproportionally affected with cognitive impairment, yet the pathophysiology linking the two conditions is unclear. Because kidney tubule secretion is essential for clearance of medications, uremic toxins, and metabolites, we hypothesized that worse tubular secretion would be associated with reduced cognitive function in CKD. METHODS: The Systolic Blood Pressure Intervention Trial tested a systolic blood pressure target <120 mmHg vs. <140 mmHg in hypertensive individuals at high cardiovascular risk. In paired blood and urine specimens from 1,937 participants with eGFR <60 ml/min/1.73m2, we measured 10 endogenous tubule-secreted metabolites and calculated a urine/plasma ratio for each, then averaged these to generate a summary secretion score. We used unadjusted and multivariable-adjusted linear regression and mixed models to evaluate cross-sectional and longitudinal associations of the secretion score with the Montreal Cognitive Assessment, Digit Symbol Coding, and Logical Memory immediate and delayed tests-measured at baseline and months 24 and 48 of follow-up. Multivariable Cox regression evaluated associations with incident probable dementia and mild cognitive impairment, adjudicated by prespecified criteria. RESULTS: Mean age was 73 ± 9 years, 41% were women, mean eGFR was 48.2 ± 11.4 ml/min/1.73m2, median albuminuria was 14.8 [7.1-48.6] mg/g. Lower secretion score was associated with a 0.06 higher adjusted logical memory delayed score (95% CI: 0.02, 0.11) but not with other cognitive tests at baseline or longitudinal cognitive decline. After a median 4.1 years of follow-up, 118 developed probable dementia and 187 developed mild cognitive impairment. Each 1-SD lower secretion score was associated with lower risk of probable dementia (HR 0.78, 95% CI: 0.63, 0.98) but not mild cognitive impairment. CONCLUSIONS: Among Systolic Blood Pressure Intervention Trial participants with CKD, lower estimated tubular secretion was not associated with worse cognition at baseline or during longitudinal follow-up.

Journal Article↗