Search Results (851)

Dementia is a growing challenge for aging societies, and effective prevention depends on identifying risk factors that can be addressed early, before cognitive decline becomes clinically apparent. Declining oral and dental function, particularly tooth loss, is increasingly recognized as one such factor, and its effect on the brain extends well beyond a reduced ability to chew. This review synthesizes current evidence linking impaired oral function to cognitive decline and dementia, with a focus on nutritional and structural brain pathways. We propose that tooth loss affects the brain through two partly independent routes. The first is nutritional: tooth loss shifts the diet away from fiber- and micronutrient-rich plant foods, which may injure the brain through oxidative stress, inflammation, and gut microbiota changes; the hippocampus, a key memory region, appears especially sensitive to nutritional status. Eating alone adds a social dimension: it is associated with lower diet quality and with reduced volume in memory-related regions, an association only partly explained by diet, since the medial temporal difference persists after dietary adjustment. The second is sensory–neural: the loss of natural teeth removes sensory input from the periodontal ligament and reduces chewing, weakening signaling to the brain and its capacity for plasticity. Importantly, atrophy of the medial temporal lobe and adjacent memory-related regions, together with increased white matter damage, is detectable even in cognitively healthy older adults, and a revised Oral Frailty Five-item Checklist can identify these presymptomatic changes. Because these structural brain changes persist despite denture use and after adjusting for diet, preserving natural teeth may be an especially valuable preventive target. Overall, maintaining oral function is a promising, accessible target for dementia prevention that warrants confirmation in prospective trials. Full article

Alzheimer’s disease (AD) is an aging-related neurodegenerative disease characterized by an initial memory impairment that progresses to a widespread cerebrocortical failure, culminating in death. Understanding the molecular mechanisms that protect brain function during aging may help reveal novel targets for the development of effective treatments for the memory and cognitive deficits associated with AD. In this study, we analyzed a gene expression dataset generated from the prefrontal cortices of individuals showing no neurological or cognitive abnormalities. The gene expression profiles were used to identify candidate protective genes. We then compared the expression patterns of these genes in aging with their expression patterns in AD, thereby enabling us to pinpoint the genes that potentially contribute to brain resilience that delays or prevents aging-related dementia. We selected seven genes that are potentially protective for aging and AD, and have known homologues in Caenorhabditis elegans (C. elegans). Among these genes, SRPK2, AAK1, EFR3A and MAPK10 were previously implicated in attenuating AD-related cognitive decline. Our experiments demonstrated that all seven genes prioritized by our resilience model significantly extended the lifespan of C. elegans. Given the important relationship between neuronal functional integrity and lifespan (i.e., lifespan vs. brain health span), this work suggests the predicted AD resilience genes could serve as important candidate targets for therapeutic intervention. Full article

Falls among older adults are a major public health concern due to their association with functional decline and increased healthcare utilization. This study investigated factors associated with fall occurrence by comparing older adults enrolled in a community-based physical activity program with sedentary older adults. This observational cross-sectional study included 67 older adults: 35 participants enrolled in the Niterói 60 Up program (G60UP; 68 ± 4 years) and 32 sedentary older adults in a sedentary comparison group (SCG; 70 ± 7 years). Assessments included anthropometric measurements, medication use, Timed Up and Go (TUG), Tinetti Performance-Oriented Mobility Assessment, Mini-Mental State Examination (MMSE), Pittsburgh Sleep Quality Index (PSQI), and orthostatic testing. Compared with the SCG, G60UP participants reported fewer falls during the previous year (0.26 ± 0.51 vs. 0.78 ± 0.83; p = 0.005), higher Tinetti scores (24.51 ± 2.54 vs. 18.28 ± 5.94; p < 0.001), shorter TUG times (8.66 ± 1.63 vs. 13.00 ± 4.31; p < 0.001), higher MMSE scores, better sleep quality (lower PSQI scores), and lower blood pressure and abdominal adiposity indicators. In the total sample, fall occurrence was associated with lower Tinetti scores (ρ = −0.416; p < 0.001), longer TUG times (ρ = 0.321; p = 0.008), older age (ρ = 0.328; p = 0.007), higher Conicity Index (ρ = 0.281; p = 0.021), and poorer sleep quality (ρ = 0.243; p = 0.047). No variable remained independently associated with falls in the exploratory multivariable logistic regression model. Participants enrolled in the 60 Up program presented more favorable functional, cognitive, sleep-related, and health-related profiles than those in the SCG. Due to the cross-sectional design, these findings should be interpreted as associations rather than causal relationships. Full article

Age-related changes in neurotransmitter systems contribute to declines in cognitive, emotional, and motor function, yet the biological mechanisms linking these changes to aging are not completely understood. Epigenetic regulation offers a promising framework to bridge this gap. DNA methylation-based biomarkers of biological aging (i.e., epigenetic clocks) capture cumulative and dynamic aspects of biological aging that may reflect vulnerability in neural systems beyond chronological age. However, whether these indices track with the integrity of neurotransmitter systems has not been systematically examined. This scoping review synthesizes evidence across human studies to evaluate how epigenetic aging processes influence neurotransmitter gene regulation and system function across the lifespan. We included 109 studies spanning 2005–2026. GABAergic genes (GAD1, GABRA2) showed the most consistent and reproducible age-related promoter hypermethylation across the cortex, inversely correlated with mRNA expression and corroborated by MRS evidence of cortical GABA decline. Dopaminergic and serotonergic evidence during normative aging was sparse; most epigenetic data in these systems came from disease cohorts. Histone modifications converged on neurotransmission and synaptic-plasticity loci, predominantly in Alzheimer’s disease tissue. Subcortical and brainstem nuclei central to monoaminergic and cholinergic systems remain under-investigated for normative aging epigenetic processes. Environmental and social determinants, socioeconomic status, childhood adversity, and chronic stress, were consistently associated with accelerated peripheral epigenetic aging, but brain-specific data are scarce. Full article

Alzheimer’s disease (AD) is characterized by cognitive decline and amyloid-β (Aβ)-related pathology. Non-rodent models that capture selected aspects of human AD remain limited. We established and characterized a human APP-driven, Aβ-related AD-like tree shrew model following AAV-mediated delivery of triple-mutant human amyloid precursor protein (hAPP-SLA) carrying the Swedish, Austrian, and London mutations by bilateral stereotaxic injection directed at CA1 coordinates. Adult tree shrews received bilateral AAV-hAPP-SLA injections directed at CA1 coordinates and were evaluated by bioluminescence imaging, behavioral testing, PCR, RT-qPCR, Western blotting, ELISA, and histopathology. Vector-associated reporter signals remained detectable for 6 months. The experimental group showed exogenous hAPP expression and reduced endogenous tsAPP expression, increased relative hippocampal Aβ₄₂ protein level, enhanced 4G8-reactive APP/Aβ-related signals, elevated total Aβ immunoreactivity, increased serum Aβ₄₂/Aβ₄₀ ratio, cytoarchitectural alterations, reduced Nissl staining, and Thioflavin S-reactive aggregate-associated signals. AT8 (Ser202/Thr205), GFAP, and Iba-1 immunoreactivity increased, whereas Synaptophysin and PSD-95 immunoreactivity was reduced. These changes were accompanied by reduced short-delay recognition-related performance and reduced social approach and social novelty preference. Aged tree shrews showed partly overlapping alterations. This model provides a non-rodent platform for studying human APP-driven Aβ-related pathology. Full article

The growing aging population is a primary driver of chronic, long-term health conditions. The rising prevalence of cognitive decline in older populations is a pressing public health issue due to its impact on health and social care and its emotional toll on family members. A lesser-known condition is sarcopenia—the age-related debilitating loss of skeletal muscle mass and function which leads to weakness and loss of mobility, quality of life and social independence. Neither health condition has a clear pharmacological treatment pathway. Diet and nutrition have therefore received the most attention for disease prevention. This review evaluates the research on the association between sarcopenia and cognitive decline and how both conditions may be linked to protein intake. While findings can be inconclusive or contradictory, a higher consumption of protein may protect against declines in physical and cognitive health, either acting separately or synergistically with exercise. The evidence supports the recommendation for a daily intake of protein higher than the current guideline of 0.8 g/kg/d for older people. Evidence suggests that healthy dietary patterns such as the Mediterranean diet appear to positively influence cognitive health in older people. Furthermore, the impact of specific high-protein foods, including egg, soy and dairy foods, on cognitive health has been reviewed, again with a suggestion that their consumption may mitigate against cognitive decline. Functional foods aimed at the aging population who wish to increase their protein intake and avert or delay the onset of these health conditions could play an important role in preventive nutrition, especially if they are formulated around the protein-rich foods which appear to positively impact cognitive health. Full article

Background and Clinical Significance: Beta-propeller protein–associated neurodegeneration (BPAN), also known as static encephalopathy of childhood with neurodegeneration in adulthood (SENDA), is a subtype of neurodegeneration with brain iron accumulation caused by pathogenic variants in WDR45. Although its clinical course and neuroimaging features are increasingly recognized, detailed neuropathological characterization, especially at its terminal stage, remains limited. Case presentation: We report a 68-year-old woman with a heterozygous WDR45 splice-site variant (NM_007075.4:c.830+1G>A), representing the longest-surviving case of SENDA/BPAN described to date. After static developmental delay in childhood, she rapidly developed progressive parkinsonism, dystonia, and cognitive decline in early adulthood, ultimately becoming bedridden with profound motor and autonomic dysfunction. Serial MRI demonstrated progressive cerebral and cerebellar atrophy with iron-related signal changes in the globus pallidus and substantia nigra. She died of sepsis at the age of 68 and was subjected to an autopsy including the brain. Neuropathological findings: Autopsy revealed severe, diffuse neuronal loss and gliosis throughout the central nervous system, with marked iron deposition and complete neuronal loss in the globus pallidus and substantia nigra. Immunohistochemistry demonstrated widespread tau pathology. Notably, neuronal tau inclusions contained both four-repeat (4R) and three-repeat (3R) isoforms, whereas glial tau was predominantly 4R-positive, indicating a mixed neuronal 4R/3R and glial 4R-dominant tauopathy. Perivascular and subpial 4R-tau–dominant deposits consistent with aging-related tau astrogliopathy were also present. LC3-positive and ferritin-positive cells suggested impaired autophagic flux, supporting the proposed autophagy-related pathogenesis of SENDA/BPAN. Conclusions: This case provides comprehensive clinicopathological insight into end-stage SENDA/BPAN, highlighting distinctive tau isoform patterns in neurons versus glia and pathological evidence of autophagy dysfunction. These findings expand the neuropathological spectrum of SENDA/BPAN and may inform future mechanistic and therapeutic research. Full article

Background/Objectives: Age-related hearing loss is one of the most prevalent chronic conditions in older adults and has emerged as a potentially modifiable risk factor for cognitive decline and dementia. Increasing evidence from epidemiological, neurobiological, and interventional studies has improved our understanding of the complex relationships between auditory dysfunction and cognitive aging. By highlighting findings in these areas, this review aims to aid clinicians and researchers gain a better understanding of the association between hearing loss, cognitive decline and dementia, and the importance of considering sensory decline during cognitive screening. Methods: This narrative review summarizes and integrates findings from epidemiological, neurobiological, and clinical studies examining relationships between hearing loss, cognitive decline, and dementia. Particular focus was placed on epidemiological associations, proposed mechanistic pathways, implications for screening and diagnostic assessment, and evidence regarding hearing rehabilitation interventions. Results: Accumulating evidence indicates that hearing loss is associated with accelerated cognitive decline and increased dementia risk. Proposed mechanisms include increased cognitive load, reduced sensory input, social isolation, depression, and shared neurodegenerative or vascular pathology, although causal pathways remain incompletely understood. Emerging evidence suggests that hearing rehabilitation may help preserve cognitive function in some groups, but findings remain heterogeneous. Clinical studies further support the importance of considering auditory function during cognitive assessment, as unrecognized hearing impairment may influence test performance, communication, and diagnostic accuracy. Conclusions: Current evidence supports hearing loss as an important factor in cognitive aging and dementia research and highlights the potential value of integrating hearing assessment and management into clinical and research settings. Full article

Background/Objectives: For low-grade glioma (LGG) patients, adjuvant treatment (AT) with radiotherapy and chemotherapy may adversely impact cognition. However, existing evidence is limited by methodological heterogeneity and shortcomings. This study explored the cognitive functioning of LGG patients who underwent resection with both radiotherapy and chemotherapy (AT+) or without AT (AT−), from before resection to one year after resection. Methods: We included patients with World Health Organization 2021 grade 2 isocitrate dehydrogenase-mutated glioma who underwent resection between 2011 and 2024. All patients completed a neuropsychological screening battery one week before (T0) and twelve months after resection (T12), measuring reaction time, attention span, information processing speed, working memory, inhibition, cognitive flexibility, and verbal fluency. We compared cognitive performance between AT+ and AT− patients at T0 and T12, as well as trajectories of cognitive functioning, at the group and individual level. Results: We included 60 LGG patients (M age = 38.8 years; 63.3% male). Compared to AT− patients (n = 35), AT+ patients (n = 25) were significantly older, more frequently had tumors that crossed the midline, and reported more depressive symptoms. At T0, no significant cognitive performance differences existed between AT+ and AT− patients, despite lower observed performance in the AT+ group. At T12, AT+ patients performed significantly worse than AT− patients on mean information processing speed, due to an improvement over time in the AT− group. Conclusions: Patients allocated to AT may show limited cognitive recovery of information processing speed up to 12 months after surgery, without pronounced effects on other cognitive functions. These findings can guide future studies into treatment-related cognitive decline of LGG patients. Full article

Background: As the population ages, dementia poses a critical public health challenge. This study examined the oral health and nutritional status of institutionalized Portuguese adults with dementia, exploring their interrelated predictors. Methods: This multicenter, cross-sectional study assessed institutionalized patients using the Decayed, Missing, and Filled Teeth (DMFT) index, posterior functional units (PFUs), plaque (PI) and gingival (GI) indices, the Short Xerostomia Inventory (SXI-5), and the Mini Nutritional Assessment (MNA). DMFT was modeled using multivariable ordinary least squares (OLS) regression for demographic and clinical predictors and separate negative binomial models for medication-related predictors. Other outcomes were analyzed using outcome-specific multivariable models. Results: The study included 71 participants (mean age: 82.5 ± 6.9 years). A high dental disease burden (mean DMFT score of 24.3 ± 7.5) was observed, independently predicted by advanced age (β = 0.48, p = 0.002) and residence in public long-term care units (LTCUs) (β = 6.65, p = 0.001). Total edentulism affected 28.2% of the sample. Polypharmacy emerged as a significant predictor of tooth loss; each additional medication was associated with an 18% decrease in the likelihood of retaining natural teeth (OR = 0.82, p = 0.008). Higher cognitive decline (GDS) was associated with increased plaque (p = 0.043), and modified-texture diets were associated with lower plaque levels (β = −0.64, p = 0.021). The mean MNA score (16.9 ± 3.8) indicated a high risk of malnutrition, with a trend toward lower gingival inflammation with better nutritional status (p = 0.061). Conclusions: Institutionalized dementia patients face severe oral and nutritional risks associated with age, polypharmacy and institutional environment. This emphasizes the need for multidisciplinary protocols and caregiver training. Full article

Background/Objectives: Cognitive impairment can compromise toothbrushing and other oral self-care functions, increasing the risk of oral diseases and related complications. However, how toothbrushing ability declines across stages of cognitive impairment remains unclear. This study aimed to describe functional deficits in toothbrushing among older adults with different levels of cognitive function. Method: Sixty-five older adults (14 cognitively healthy and 51 with documented cognitive impairment) were classified into five cognitive levels based on Standardized Mini-Mental State Examination scores. Participants completed a toothbrushing task as they normally would at home. Performance was videotaped, coded, and evaluated across four domains (task initiation, completion, thoroughness, and quality) with total scores reflecting overall toothbrushing ability. Overall performance, functional deficits, and assistance needs were analyzed in relation to cognitive levels. Results: Participants averaged 76.5 years of age. Toothbrushing ability declined gradually with worsening cognitive impairment, followed by a sharp deterioration at the profound stage (e.g., SMMSE ≤ 5). Compared with cognitively healthy participants (n = 14), those with mild cognitive impairment (MCI, n = 20) or mild (n = 10), moderate (n = 10), or severe dementia (n = 11) lost an average of 3%, 8%, 12%, and 37% of overall toothbrushing ability, respectively. Brushing efficiency declined earlier and more rapidly, decreasing by 13% in MCI and up to 46% in severe dementia (p < 0.001). All participants with MCI or mild dementia completed the task independently, whereas 20% with moderate dementia and 80% with severe dementia required assistance to initiate or complete the task. Conclusions: Overall toothbrushing ability remains relatively preserved until the later stages of cognitive impairment, but brushing quality deteriorates much earlier and quicker. These findings highlight the importance of early caregiver–patient partnerships, functionally tailored oral self-care rehabilitation, and personalized caregiver training to support oral hygiene among older adults with cognitive impairment. Full article

Background: Given the increasing consumption of ultra-processed foods (UPFs) and the public health importance of cognitive decline in ageing, understanding how UPFs impact cognitive performance is highly relevant. However, evidence in older adults—particularly in Italy—remains scarce, despite the country’s rapidly ageing population, its comparatively low UPF intake, and its distinct Mediterranean dietary context. Methods: We analysed cross-sectional data from 809 community-dwelling adults aged ≥ 65 years (59.4% women) participating in the NutBrain population-based cohort. Dietary intake was assessed using a 102-item semi-quantitative food frequency questionnaire, and daily grams of foods were classified according to the NOVA system into groups, which were analysed using a compositional data analysis approach. Global cognition and domain-specific performance were measured using standardised neuropsychological tests. Associations between NOVA groups and cognitive outcomes were estimated using multiple linear regression models adjusted for potential confounders. Gender-stratified analyses were also performed. Results: UPFs accounted for 21% of total energy intake, with bakery products as the main contributors. A relative increase of unprocessed or minimally processed foods was associated with better cognitive function (B = 0.36, p = 0.014), whereas a greater contribution of UPFs relative to the overall diet was associated with worse global cognitive function (B = −0.26, p = 0.003). The strongest associations were observed for episodic memory, particularly among women. Conclusions: A higher relative consumption of UPF was associated with worse global and memory-related cognitive performance. Longitudinal and experimental studies are warranted to clarify causality and underlying mechanisms. Full article

Background: Vitamin D deficiency is highly prevalent in older adults and has been increasingly recognised as a potential contributor to cognitive decline, depressive symptomatology, and functional impairment. However, the clinical significance of specific 25-hydroxyvitamin D thresholds in relation to this multidomain geriatric phenotype remains incompletely characterised. Methods: We conducted a cross-sectional study of 1438 consecutive patients aged 65 years or older admitted for comprehensive geriatric assessment at a tertiary centre in Cluj-Napoca, Romania, between January 2023 and November 2025. Serum 25-hydroxyvitamin D [25(OH)D] was categorised as deficient (<20 ng/mL), insufficient (20–30 ng/mL), or sufficient (≥30 ng/mL). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), depressive symptoms using the Geriatric Depression Scale (GDS-30 and GDS-SF), and functional status using Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL). Multivariable linear regression analyses were adjusted for age, body mass index, serum albumin, and estimated glomerular filtration rate (eGFR). Results: Suboptimal vitamin D status was highly prevalent in this geriatric cohort, with 43.3% of participants meeting criteria for frank deficiency (<20 ng/mL). Lower 25(OH)D concentrations were significantly associated with worse cognitive performance, greater depressive symptom burden, and higher functional dependency. Serum 25(OH)D correlated positively with MoCA and MMSE scores and inversely with ADL, IADL, and GDS scores. In adjusted models, vitamin D remained independently associated with MoCA, IADL, and GDS. Stratified analyses suggested that the main clinical deterioration occurred below 20 ng/mL, while the 20–30 ng/mL range behaved as an intermediate phenotype closer to sufficiency than to frank deficiency. Conclusions: In this large cohort of hospitalised older adults, serum 25(OH)D deficiency below 20 ng/mL was independently associated with poorer cognition, more depressive symptoms, and greater functional impairment. These findings support routine vitamin D assessment in geriatric practice and suggest that the <20 ng/mL threshold identifies a clinically relevant high-risk phenotype. Full article

Introduction: Sleep disturbances are common as we age and have been linked to poor cognition and increased cognitive decline. Objective: We aimed to examine cross-sectional and longitudinal associations between objective sleep measures and cognition in middle-aged and older adults, including cognitively healthy (CH) individuals and those with mild cognitive impairment (MCI). Methods: Participants from the Aiginition Longitudinal Biomarker Investigation Of Neurodegeneration (ALBION) study (age > 40) underwent 7-day wrist actigraphy (Actiwatch 2). Sleep exposures included sleep duration, sleep efficiency, sleep variability, sleep onset latency, wake after sleep onset (WASO), and number of awakenings. A neuropsychological battery was administered examining memory, executive function, visuospatial ability, language, attention speed, and a global composite score. Cross-sectional associations were tested using generalized linear models (adjusted for age, sex, education). Longitudinal associations with cognitive trajectories were examined with linear mixed-effect models. Results: In total (N = 184; 65% women; mean age 65 years), average sleep duration was 7.2 h and mean sleep efficiency was at 80%. Cross-sectionally, more nightly awakenings were associated with poor memory and attention speed. In a 1.5-year follow-up, (n = 93), higher baseline sleep efficiency was associated with better memory and language performance, while longer WASO, more awakenings, and longer sleep onset latency showed nominal associations with less favorable cognitive trajectories, although these associations did not remain statistically significant after FDR correction. Time-varying analyses indicated that sleep variability showed robust non-linear associations with poorer memory trajectories over follow-up and remained significant after FDR adjustment; significant mean change in awakenings and variability appeared to intensify in later follow-up phases. The association between sleep characteristics and cognitive decline varied across follow-up time, with stronger adverse changes observed during later follow-up phases. Discussion: Objective indicators of sleep continuity, especially sleep variability, were most consistently related to domain-specific cognitive outcomes, with strongest evidence for memory over time. Sleep fragmentation and irregular sleep patterns may represent potentially modifiable targets for future strategies aimed at preserving cognitive health during aging. Full article

Background/Objectives: Ultra-processed foods (UPFs) are increasingly recognized as dietary exposures associated with cardiometabolic, hepatic, and neurocognitive outcomes. However, UPFs are often treated mainly as nutrient-poor foods, whereas their processing-related features may perturb gut–liver–brain communication. This review examines whether metabolic dysfunction-associated steatotic liver disease (MASLD) can be conceptualized as a hepatic metabolic amplifier linking UPF exposure to cognitive aging. Methods: We conducted a structured narrative search of PubMed/MEDLINE, Web of Science Core Collection, and Scopus from January 2010 to 11 May 2026 across four evidence modules: UPFs and MASLD/NAFLD; UPFs and cognitive aging or dementia; UPFs and gut–liver–brain mechanisms; and MASLD/NAFLD and cognitive aging. Representative studies were prioritized according to direct relevance to the proposed axis, study design, exposure and outcome validity, mechanistic specificity, and contribution to major evidence gaps. Results: Observational and mechanistic evidence links higher UPF consumption with liver steatosis, MASLD/NAFLD-related outcomes, cognitive decline, cognitive impairment, stroke, and dementia-related outcomes, although causality remains incompletely established and residual confounding is important. Candidate pathways include food-matrix disruption, rapid eating, displacement of microbial substrates, selected additives and processing-derived compounds, intestinal barrier dysfunction, metabolic endotoxemia, bile acid signaling, hepatic lipotoxicity, systemic inflammation, vascular dysfunction, and neuroimmune activation. Many pathways overlap with general cardiometabolic dysfunction; the processing-centered contribution lies in positioning industrial formulation as an upstream exposure and MASLD as a hepatic node that may amplify gut-derived and metabolic signals relevant to brain aging. Conclusions: A processing-centered gut–liver–brain framework integrates UPFs, MASLD, and cognitive aging as linked metabolic-aging phenomena. Future studies should test UPF substitution using liver imaging, microbiome profiling, metabolomics, bile acid and inflammatory biomarkers, neuroimaging, and cognitive assessment. Full article