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PubMed2026

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n = 15,765) consisted of UK Biobank participants (MDD only n = 1230; T2DM only n = 3644; comorbid T2DM + MDD n = 721). Individuals with T2DM + MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR = 4.44, 95% CI = [3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM + MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM + MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM + MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans↗

PubMed2026

Polygenic Risk Scores for Incident Dementia in the Multi-Ethnic Study of Atherosclerosis.

Over 75 Alzheimer's disease (AD) and dementia-associated variants have been identified through genome-wide association studies, but the utility of polygenic risk scores (PRS) for predicting AD and dementia in diverse and admixed populations remains unclear. We compared how PRS approaches differing in p-value thresholds, variant weights, and source ancestry perform in predicting dementia in 6338 African American, Chinese, Hispanic, and White individuals from the Multi-Ethnic Study of Atherosclerosis. We tested clumping and thresholding (C+T) methods with varying parameters against Bayesian approaches (PRS-CS, PRS-CSx). We compared the ability of each method to predict incident dementia in all participants and in groups stratified by self-reported race/ethnicity. We additionally analyzed performance across groups stratified by estimated proportion of non-Finnish European (NFE)-like ancestry. Including more variants does not improve performance. We found comparable associations between dementia and PRS when comparing a C+T method with only 15 SNPs and PRS derived from Bayesian models that include > 800,000 SNPs (HR5e-08 = 1.18, 95% CI: 1.08-1.28; HRCSx = 1.17, 95% CI: 1.07-1.27). The p < 5e-08 C+T method was more strongly associated with incident dementia in populations genetically dissimilar from the source data (HRlowNFE_5e-08 = 1.27, 95% CI: 1.08-1.50; HRlowNFE_CSx = 1.12, 95% CI: 0.94-1.33). More selective PRS models using genome-wide significant SNPs may be preferable for dementia prediction in diverse populations.

Aged↗

PubMed2026

Association between oxidative balance score and cardiovascular risk factors, aging, and incidence of dementia risk score: A prospective cohort study.

BackgroundOxidative stress is a key contributor to the pathogenesis of Alzheimer's disease and other dementias. The oxidative balance score (OBS), which reflects combined dietary and lifestyle exposure to pro-oxidant and antioxidant factors, serves as an integrated measure of oxidative stress burden.ObjectiveTo investigate the association between OBS and predicted late-life dementia risk using the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score.MethodsWe analyzed data from 5088 participants aged 40-69 years without dementia at baseline from the Korean Genome and Epidemiology Study. Participants were categorized by OBS tertiles. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for developing a high risk of late-life dementia, defined by a CAIDE score ≥8. Longitudinal changes in CAIDE scores were assessed using linear mixed-effects models.ResultsDuring a mean follow-up of 12.8 years, 1468 participants (28.9%) progressed to CAIDE-predicted high risk for late-life dementia. Compared with the lowest OBS tertile (T1), participants in the highest tertile (T3) had a significantly lower risk for developing high-risk late-life dementia (HR 0.74, 95% CI 0.65-0.84) and exhibited the lowest CAIDE scores (p < 0.001). Each one-point increase in the OBS was associated with a 3% reduction in CAIDE-predicted dementia risk.ConclusionsA higher OBS was significantly associated with a lower predicted risk of late-life dementia. These findings suggest that maintaining an antioxidant-rich diet and a healthy lifestyle during midlife may be effective strategies for dementia prevention.

Alzheimer's disease↗

PubMed2026

The interplay between impaired kidney function and hypertension in dementia: A 13-year longitudinal study.

BackgroundHypertension and kidney function impairment (KFI) are established risk factors for dementia and may reinforce each other. However, whether their coexistence confers excess dementia risk remains unclear.ObjectiveTo examine the multiplicative and additive interactions between hypertension and KFI in relation to incident dementia and explore potential biological pathways.MethodsWe included 218,858 dementia-free adults followed for a mean of 13.2 years. KFI was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. Cox proportional hazards models assessed independent associations and multiplicative interaction, while additive interaction was evaluated using the relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). Plasma proteomic data on 2911 proteins were available for 6127 participants.ResultsHypertension was associated with dementia risk (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.17-1.31; p < 0.001), whereas KFI was not (HR, 1.02; 95% CI, 0.94-1.11; p = 0.571). A significant multiplicative interaction was observed (p = 0.018). KFI was associated with dementia only among participants with hypertension (HR, 1.15; 95% CI, 1.01-1.29; p = 0.023). A positive additive interaction was also observed (RERI, 0.27; 95% CI, 0.05-0.49; AP, 0.17; 95% CI, 0.05-0.29; SI, 1.84; 95% CI, 1.11-3.07), although it was attenuated after full adjustment. Proteomic analyses implicated immune and inflammatory pathways.ConclusionsHypertension may modify the association between impaired kidney function and dementia risk. Their coexistence may identify individuals at higher risk, but further studies are needed to confirm these findings and clarify the underlying mechanisms.

Humans↗

PubMed2025

The Role of Genomic-Informed Risk Assessments in Predicting Dementia Outcomes.

INTRODUCTION: By integrating genetic and clinical risk factors into genomic-informed dementia risk reports, healthcare providers can offer patients detailed risk profiles to facilitate understanding of individual risk and support the implementation of personalized strategies for promoting brain health. METHODS: We constructed an additive score comprising the modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Score (mCAIDE), family history of dementia, APOE genotype, and an AD polygenic risk score in NACC and ADNI, and assessed its association with progression to all-cause dementia. RESULTS: 81% of participants had at least one high-risk indicator for dementia, with each additional risk indicator linked to a 34% increase in the hazard of dementia onset. DISCUSSION: We found that most participants in memory and aging clinics had at least one high-risk indicator for dementia. Furthermore, we observed a dose-response relationship where a greater number of risk indicators was associated with an increased risk of incident dementia.

dementia risk scores↗

PubMed2025

Associations Between Walking Pace, APOE-ε4 Genotype, and Brain Health in Middle-Aged to Older Adults.

PURPOSE: This study aimed to investigate whether self-reported walking pace (a marker of physical function) and the presence of APOE-ε4 allele interact to modify brain health outcomes. METHODS: We used data from a prospective cohort study of middle-aged to older adults from the UK Biobank who self-reported walking pace (slow or steady-to-brisk) and who were initially free of dementia ( n = 415,110). Incident all-cause dementia was obtained from hospital and death registry records, and structural brain volumes (right and left hippocampus volumes, total gray matter volume, and volume of white matter hyperintensities) were measured from a subset of participants ( n = 33,113). Cox proportional hazard models and generalized linear models were used to assess associations between exposures and outcomes. RESULTS: Slow walking pace and the presence of APOE-ε4 allele were associated with increased dementia risk (HR = 1.79 [95% CI = 1.66-1.93], P < 0.001; HR = 3.06 [2.90-3.23], P < 0.001, respectively), and there was an interaction between these associations, indicating that the association of walking pace with dementia risk is modified by APOE-ε4 status (reference group: HR Steady-Brisk/APOE-ε4- = 1; HR Slow/APOE-ε4- = 2.03 [1.84-2.25], P < 0.001; HR Steady-Brisk/APOE-ε4+ = 3.21 [3.02-3.41], P < 0.001; HR Slow/APOE-ε4+ = 4.99 [4.48-5.58], P < 0.001). Slow self-reported walking pace was associated with worse brain volume outcomes, and these associations were not modified by APOE-ε4 genotype. CONCLUSIONS: These results suggest walking pace and APOE-ε4 status independently influence brain volume outcomes, but both factors independently and jointly contribute to increased dementia risk. Individuals with both risk factors (slow walking pace and APOE-ε4 allele) show the strongest associations with dementia risk.

Self Report↗

PubMed1979

Dementia in Parkinson Disease.

In 520 patients with parkinsonism seen over eight years, 168 (32%) had moderate to marked dementia. Although the demented patients were older than the nondemented patients (70.4 versus 65.5 years), the incidence of dementia in Parkinson's disease (PD) was tenfold higher than among controls (similarly aged spouses of PD patients), and dementia is held to be related more to the disease than to age. Demented patients, in addition to being older, developed PD later, were more severely involved in a shorter time, and responded less well to levodopa. It is suggested that PD with dementia may represent a different disorder from PD without dementia.

Aged↗

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↗

PubMed1979

Myocardial infarction in the differential diagnosis of dementias in the elderly.

The incidence of cerebral lesions in relation to myocardial infarction (MI) was evaluated on the basis of data obtained from medical records and autopsy reports on 269 psychogeriatric patients, in a 13-year retrospective study. Among 84 demented patients with MI, brain infarcts and hemorrhages were found in 42 percent, and Alzheimer's disease in 17 percent; (combination in 8 percent). In contrast, among 70 demented patients without MI, brain infarcts and hemorrhages were found in 11 percent, and Alzheimer's disease in 43 percent; (combination in 6 percent). Therefore, when it is difficult to differentiate senile dementia (Alzheimer's disease) from dementia due to cerebrovascular impairment, data on the presence or absence of myocardial infarction may prove useful.

Aged↗

PubMed2026

Plasma Proteomic Signatures of Physical Activity Provide Insights into Biological Impacts and its Protective Role against Dementia.

PURPOSE: Physical activity (PA) and sedentary behavior (SB) are associated with many diseases, including Alzheimer disease and all-cause dementia. However, the specific biological mechanisms through which PA protects against disease are not entirely understood. This study aims to address this gap, with a specific focus on all-cause dementia. METHODS: We first assessed the conventional observational associations of three self-reported and three device-based PA/SB measures with circulating levels of 2911 plasma proteins measured in the UK Biobank ( nmax = 39,160) and assessed functional enrichment of identified proteins. We then used bidirectional Mendelian randomization to further evaluate the evidence for causal relationships of PA/SB with protein levels. Finally, we performed mediation analyses to identify proteins that may mediate the relationship of PA with incident all-cause dementia. RESULTS: Our findings revealed 41 proteins consistently associated with all PA measures and 1027 proteins associated with at least one PA measure. Both conventional observational and Mendelian randomization study designs converged on proteins that appear to increase as a result of PA, including integrins such as ITGAV and ITGAM, as well as MXRA8, CLEC4A, CLEC4M, LPL, and ADGRG2; and on proteins that appear to decrease as a result of PA such as LEP, INHBC, CLMP, PTGDS, ADM, OGN, and PI3; and on proteins that are more responsive to high-intensity PA, such as CA14, CA6, CA4, KIT, and ANGPT2. Functional enrichment analyses revealed processes such as cell-matrix adhesion, integrin-mediated signaling, and collagen binding. Finally, GDF15, ITGAV, ITGAM, ITGA11, HPGDS, GFAP, ADM, AHNAK, and DPP4 were among 21 unique proteins found to mediate the relationship of PA with all-cause dementia, implicating processes such as synaptic plasticity, neurogenesis, and inflammation. CONCLUSIONS: Our results provide insights into how PA affects biological processes and protects against dementia, and provide avenues for future research into the health-promoting effects of PA.

Humans↗

PubMed1979

[Down syndrome: immunological study in adults (author's transl)].

The immunological profile was evaluated in 12 adults affected by Down's syndrome. Our findings showed: increase of serum IgG, IgA and Gammaglobulins, decrease of IgM, presence of auto-antibodies and increased antibodies response after antigenic stimulation (typhoid vaccination). Some tests, connected with T lymphocytes functions, were also abnormal: percentage of E-active rosettes, cutaneous sensibilization with DNCB and lymphocyte stimulation index with PHA. Our findings suggest a T lymphocyte deficit, with loss of immunological surveillance and therefore of the control over antibody mediated immunological reactions. The immunological alterations observed in our adult patients with Down's syndrome were more extensive and severe than those found in young subjects. The possible relevance of these findings is discussed as well as the incidence of Alzheimer's dementia in adult patients with Down's syndrome.

Adult↗

PubMed1979

Diagnostic accuracy in presenile dementia.

A follow-up study of patients diagnosed as suffering from presenile dementia has revealed a high incidence of erroneous diagnoses. Of 52 patients discharged from hospital with this diagnosis, information was obtained 5-15 years later on 51. Eighteen were alive and the diagnosis was rejected in 16 (31 per cent). Possible reasons for the mistaken diagnoses are discussed.

Aged↗

PubMed2022

Abdominal aortic calcification on lateral spine images captured during bone density testing and late-life dementia risk in older women: A prospective cohort study.

BACKGROUND: Dementia after the age of 80 years (late-life) is increasingly common due to vascular and non-vascular risk factors. Identifying individuals at higher risk of late-life dementia remains a global priority. METHODS: In prospective study of 958 ambulant community-dwelling older women (≥70 years), lateral spine images (LSI) captured in 1998 (baseline) from a bone density machine were used to assess abdominal aortic calcification (AAC). AAC was classified into established categories (low, moderate and extensive). Cardiovascular risk factors and apolipoprotein E (APOE) genotyping were evaluated. Incident 14.5-year late-life dementia was identified from linked hospital and mortality records. FINDINGS: At baseline women were 75.0 ± 2.6 years, 44.7% had low AAC, 36.4% had moderate AAC and 18.9% had extensive AAC. Over 14.5- years, 150 (15.7%) women had a late-life dementia hospitalisation (n = 132) and/or death (n = 58). Compared to those with low AAC, women with moderate and extensive AAC were more likely to suffer late-life dementia hospitalisations (9.3%, 15.5%, 18.3%, respectively) and deaths (2.8%, 8.3%, 9.4%, respectively). After adjustment for cardiovascular risk factors and APOE, women with moderate and extensive AAC had twice the relative hazards of late-life dementia (moderate, aHR 2.03 95%CI 1.38-2.97; extensive, aHR 2.10 95%CI 1.33-3.32), compared to women with low AAC. INTERPRETATION: In community-dwelling older women, those with more advanced AAC had higher risk of late-life dementia, independent of cardiovascular risk factors and APOE genotype. Given the widespread use of bone density testing, simultaneously capturing AAC information may be a novel, non-invasive, scalable approach to identify older women at risk of late-life dementia. FUNDING: Kidney Health Australia, Healthway Health Promotion Foundation of Western Australia, Sir Charles Gairdner Hospital Research Advisory Committee Grant, National Health and Medical Research Council of Australia.

AAC, abdominal aortic calcification↗

PubMed1979

Neurofibrillary degeneration on Guam: frequency in Chamorros and non Chamorros with no known neurological disease.

In a neuropathological study of the brains of 69 members of the Guamanian Chamorro population without known evidence of dementia, parkinsonism or amyotrophic lateral sclerosis, the incidence and severity of neurofibrillary degeneration was determined in relation to age at death. It was found that neurofibrillary degeneration is present at an earlier age than has been reported for a comparable population in Japan, and much earlier than reported for two similarly comparable English populations. Our data suggests that neurofibrillary degeneration is the common denominator of the Guam neurological syndromes of parkinsonian dementia, amyotrophic lateral sclerosis and dementia without parkinsonism. This conclusion would imply that the aetiological factor of neurofibrillary degeneration is more widely dispersed in the population than suggested by the cases of parkinsonian dementia and amyotrophic lateral sclerosis alone. Both sexes were equally affected while clinical parkinsonian dementia is three times more frequent among males. The sample data suggests a positive association with the amyotrophic lateral sclerosis-parkinsonian dementia rate in village of birth and residence, and also with family history; the results in the small subsamples are not significant. Senile plaques were found in few control cases in this study, just as there has been a relative absence of senile plaques in cases of parkinsonian dementia. In a small group of Caucasians who had spent many of their adult years on Guam, the frequency of neurofibrillary degeneration in relationship to age was comparable to that in the English populations.

Adolescent↗

PubMed1979

Lewy bodies in the presence of Alzheimer's disease.

Large numbers of Lewy bodies in the substantia nigra were found in a case of Alzheimer's disease. Parkinsonian symptoms were not recognized. The patient appears to be an example of an association recognized by Woodard but not yet understood. The case is discussed in the context of reported relationships between Parkinson's disease or "Lewy body disease" and dementia, on the one hand, and reports linking various forms of psychoses with an unusually high incidence of Lewy bodies, on the other.

Aged↗

PubMed2026

Effects of comprehensive oral care on nasogastric tube removal in long-term care residents with dysphagia: A multi-center randomized controlled trial.

Oral care is essential for residents in long-term care (LTC) facilities to reduce complications such as aspiration pneumonia. While routine oral hygiene is standard practice, comprehensive oral care (COC)-which includes facial and intraoral muscle massage, salivary gland stimulation, and oral moisturization-may further enhance swallowing function. However, evidence linking COC directly to nasogastric (NG) tube removal remains limited. This study evaluated the effectiveness of COC in facilitating NG tube removal and improving swallowing function among LTC residents with dysphagia. A multicenter, open-label randomized controlled trial was conducted across eight LTC facilities. The intervention group (n = 40) received daily one-on-one COC sessions lasting 30-40 min, while the control group (n = 37) received routine oral hygiene. Participants were followed for six months, with outcomes including NG tube removal, swallowing function, body weight, and pneumonia incidence. At six months, the COC group demonstrated a significantly higher NG tube removal rate, with eight participants achieving full oral intake (p = 0.005). Functional Oral Intake Scale scores were also significantly higher in the intervention group (p = 0.005). Time to NG tube removal ranged from 17 to 182 days. Under intention-to-treat principles, the NG tube removal rate remained significantly higher in the COC group (16.7%vs. 0%, p = 0.005). Competing risks analysis using the Aalen-Johansen estimator confirmed a 6-month cumulative incidence of NG tube removal of 14.6% in the COC group versus 0% in the control group (Gray's test: p = 0.005), with no significant between-group difference in mortality (p = 0.500). No significant differences were observed in body weight change or pneumonia incidence between groups. Among participants who successfully discontinued NG tube use, dementia was the most common underlying condition. These findings suggest that daily one-on-one COC is a feasible intervention in LTC settings and may improve swallowing function while facilitating NG tube removal in residents with dysphagia.

Humans↗

PubMedDate not supplied

[Natural history of Huntington's chorea].

The scope of the work is to list and analyse, after a historical introduction on the subject, the principle clinical characteristics of "Huntington's Disease". The epidemiological aspects, those clinical-semeiotical, the course of the disease and the type of after affects of Huntington's Diseases are examined. The more significant details of the natural history of the chorea maior, as emerge from the literature, are compared with those that result from the study of the thirty cases of this chronic disease. In particular the following are analysed, the genetic aspects, the character of the psycho-organic deterioration of the chronic chorea, the psychiatric component and various clinical-semeiotical formalities, how the disease begins, its course, its duration, etc. The authors conclude pointing out the particular character of the dementia of Huntington's Disease, (of the pre-frontal type), the strong psychopathological incidence and the particular formalities of hereditary transmission of the mendelian type of this singular disease.

Adolescent↗

PubMed1975

Search for herpetic antibodies in the cerebrospinal fluid in senile dementia and mental retardation.

Complement-requiring neutralizing antibodies to herpes simplex type 1 virus (HSV 1) in titres from 2 to greater than 16 were detected in the cerebrospinal fluid (CSF) of 47% senile patients with various forms of dementia, but in none of mentally retarded adolescents and adults suffering from various neurologidal diseases. Also the incidence of HSV 1 serum antibodies in elevated titres (larger than or equal to 512) was increased in senile demented patients (61%) as compared with persons in normal senium (31%), normal adults (15%), mentally retarded adolescents (17%) and prisoned felons with low IQ (45-47%).

Adolescent↗