Journal of Dementia and Alzheimer's Disease

Background: Sleep disturbance is highly prevalent in dementia syndromes and increasingly viewed as a correlate of disease expression, not just ageing. This study investigated associations between subjective sleep quality, cognitive performance, and structural MRI markers in a dementia syndromes sample, comparing Alzheimer’s disease (AD) and non-AD groups, with exploratory inclusion of objective sleep and nocturnal blood pressure in a sub-sample. Methods: Observational cross-sectional design with 128 memory clinic patients (41 AD, 87 non-AD). Subjective sleep quality assessed via Pittsburgh Sleep Quality Index (PSQI). Cognitive measures: Mini-Mental State Examination (MMSE) for global cognition, Symbol Digit Modalities Test (SDMT) for processing speed, Trail Making Tests (TMT-A/B), and CLOX-1/2 for executive function. MRI markers: Scheltens scale (medial temporal atrophy), Fazekas scale (white matter hyperintensities). An exploratory sub-sample (N = 24) included additional nocturnal and daytime blood pressure monitoring; these data were analyzed descriptively and are reported as hypothesis-generating only. Analyses: group comparisons, Spearman correlations, hierarchical and logistic regression models in the full sample, and descriptive analyses with Spearman correlations in the exploratory sub-sample. Results: The AD group reported poorer sleep quality (higher PSQI) and worse cognitive performance across domains compared with the non-AD group (p < 0.001). Higher PSQI scores were associated with poorer cognitive outcomes, particularly executive function and processing speed, after adjustment for demographics and structural MRI markers (e.g., β = −0.181 to −0.425 for MMSE/SDMT). In the exploratory sub-sample (N = 24), PSQI was correlated with SDMT (ρ = −0.653) and TMT-A (ρ = 0.788). Conclusions: Subjective sleep quality was associated with cognitive performance in individuals with dementia syndromes after accounting for structural MRI markers. These findings suggest that subjective sleep disturbance may represent a complementary clinical dimension warranting further longitudinal research, including evaluation of whether sleep-focused interventions may offer clinical benefits. Full article

Background/Objectives: Amyloid-PET is accurate but costly and capacity-limited. Blood-based biomarkers (BBMs), particularly plasma p-tau217, offer a scalable alternative for triaging patients. Objective of this study is to evaluate the diagnostic accuracy and clinical utility of plasma p-tau217 as a pre-screening tool for amyloid-PET positivity, identifying operating thresholds for rule-out and rule-in strategies. Methods: We analyzed 1681 participants from the ADNI cohort with concurrent plasma biomarkers (Fujirebio Lumipulse assays) and ¹⁸F-florbetapir PET. The primary outcome was discrimination of amyloid-PET positivity (Centiloid > 20). We compared p-tau217 alone against multivariable models (including Aβ42/40, GFAP, NfL, APOE) using Area Under the Curve (AUC) and Decision Curve Analysis (DCA). Two clinical thresholds were defined: a high-sensitivity “rule-out” cut-off (≥95% sensitivity) and a Youden-optimal “balanced” cut-off. These were validated using stratified bootstrap resampling. Results: Of 1681 participants, 679 (40.4%) were amyloid-positive. In the full sample, plasma p-tau217 alone achieved an AUC of 0.902 (95% CI 0.885–0.918). Operating thresholds were derived on a development split and applied to an independent validation split (N = 505). In the validation cohort, the high-sensitivity threshold (0.106 pg/mL) yielded 94.6% sensitivity and 93.7% NPV, effectively ruling out amyloid pathology. The Youden threshold (0.177 pg/mL) offered 78.9% sensitivity and 86.0% specificity. DCA demonstrated net benefit for p-tau217 screening over “PET all” strategies across clinically relevant probability ranges. Conclusions: Plasma p-tau217 provides high discrimination and clinically interpretable operating points for prioritizing confirmatory PET. Implementing a p-tau217-first strategy could significantly reduce unnecessary imaging without compromising diagnostic safety. Full article

Background/Objectives: Communication decline is a hallmark of dementia, yet speech-language outcomes remain marginal in much of the virtual reality (VR) dementia literature. This evidence review synthesises empirical work on how VR has been used to support, train, or assess communication in dementia, positioning VR as a communication platform rather than only a cognitive tool. Methods: A structured search (2000–2025) across CINAHL, PubMed, PsycINFO, Scopus, and Web of Science was supplemented by reference list checking. Eleven empirical studies met eligibility criteria, spanning immersive and non-immersive VR used with people living with dementia, and VR-based communication training for caregivers, care staff, and clinicians. Findings were synthesised thematically through an explicit communication lens. Results: Evidence most consistently supports VR as a scaffold for communicative engagement and participation. Immersive and shared VR experiences commonly elicited increased verbal involvement, shared attention, and interactional responsiveness during or immediately after sessions, particularly when content was socially meaningful and appropriately paced. A second strand of work uses VR simulation to train communication partners, with participants reporting high acceptability and perceived improvements in confidence and strategy use, although behavioural transfer to real-world care is rarely measured. Assessment-oriented studies and stakeholder perspectives highlight VR’s potential to elicit functional behaviour in context and to complement clinic-based assessment, but communication validity is typically inferred rather than operationalised using standardised measures. Conclusions: VR shows early promise for dementia communication care, especially as an adjunct that structures interaction, supports participation, and scales communication training. Progress now depends on communication-specific intervention design, agreed outcome metrics capturing discourse and functional participation, and implementation studies addressing accessibility, cultural-linguistic diversity, and transfer to everyday care. Full article

Background/Objectives: Facilities for persons with Alzheimer disease need to be adapted for them in terms of architecture and interior and exterior design, where the introduction of an artistic dimension is recommended. This raises the question of exploring the aesthetic preferences of the people concerned in order to optimise the design. We assessed whether individuals with Alzheimer’s disease can make aesthetic judgements, and if so, their nature and how stable they were over time. Methods: We compared the aesthetic preferences of 23 persons with Alzheimer’s disease matched to 23 controls. Preferences were collected using a Q-PEG questionnaire, which presents photographs of various artworks: paintings, sculptures, functional objects, and representation of living things: human, animal, and landscape, in various styles: figurative, stylized, abstract. This tool was created specifically by our team for this research; this is the first exploratory publication to use it. Results: We confirm the feasibility of collecting aesthetic judgements from individuals living with Alzheimer’s disease using the Q-PEG tool. The aesthetic judgements of both participant groups proved to be stable over time. Furthermore, the aesthetic judgements of individuals with Alzheimer’s disease did not differ from those of the controls, regardless of the style or type of artwork. These preferences are independent of the various cognitive functions assessed. Hypotheses about the Alzheimer-resistant nature of the cognitive register of aesthetic preferences are discussed. Conclusions: As they can express their artistic preferences, individuals living with Alzheimer’s disease should be consulted. These results provide insights for the design of facilities and therapeutic gardens based on evidence-based design (EBD) criteria. The integration of an artistic dimension in line with these preferences and in compliance with the general recommendations makes it possible to create adapted, specific spaces that are appreciated by all. Full article

Background: Single-target Alzheimer’s disease (AD) therapies have repeatedly failed to modify disease progression, highlighting a critical mismatch between multifactorial pathology and reductionist pharmacology. Methods: We developed a representation learning framework using Knowledge-guided Pre-trained Graph Transformers (KPGT) to enable rational multi-target drug discovery, analyzing 2446 molecules across APP, PSEN1, and VCP. Results: KPGT captured target-specific mechanistic signatures with 99.35% classification accuracy. Geometric midpoint analysis identified 15 bridging candidates with mean pIC₅₀ 8.09. We discovered two orthogonal molecular feature signatures, structural features driving multi-target breadth versus chemical features determining single-target potency, with zero descriptor overlap. Chemical orthogonality (d = 3.86) outperformed functional similarity for predicting synergistic pairs, with 95% overlap between multi-target molecules and synergistic combinations. Conclusions: This framework operationalizes systems-level AD drug discovery through interpretable representation learning. Full article

Alzheimer’s disease (AD) is the most common form of dementia marked by cognitive decline and memory loss. Early detection is essential for timely intervention; however, traditional biomarkers, including cerebrospinal fluid (CSF) assays, neuroimaging, and cognitive assessments, are limited by cost, invasiveness, and accessibility. Digital biomarkers, obtained from wearable sensors, smartphone applications, speech analysis, and other passive monitoring technologies, represent a promising alternative for scalable, non-invasive, and continuous assessment of early cognitive decline. This paper provides a comprehensive review of the current landscape of digital biomarkers for AD diagnosis, emphasizing their potential application in the preclinical and prodromal stages of the disease. In addition, a bibliometric analysis demonstrates the rapid expansion of digital biomarker research, highlighting key trends in publication volume, influential authors, institutions, and interdisciplinary collaborations. Despite the significant promise of digital biomarkers, challenges remain regarding validation, regulatory approval, data privacy, and integration into clinical practice. The results indicate that future research should prioritize standardization, multimodal biomarker integration, and large-scale longitudinal studies to fully realize the potential of digital technologies in AD detection. Full article

Background: Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are increasingly recognized as biologically heterogeneous disorders. Although biomarker-based frameworks have improved disease stratification, they may not fully capture the molecular diversity underlying disease mechanisms. This study aimed to define biologically meaningful AD and PD subtypes by employing large-scale plasma proteomics to characterize mechanism-driven patient stratification. Methods: We analyzed plasma proteomic data from the Global Neurological Proteomics Consortium (GNPC) dataset and performed disease-specific unsupervised clustering to identify molecular subtypes. We performed differential protein expression and pathway enrichment analyses to characterize subtype-specific and shared biological signatures. Results: Clustering analysis revealed three molecular AD subtypes and two PD subtypes, each exhibiting unique proteomic signatures despite similar demographic and cognitive profiles. AD subtypes differed in the relative involvement of immune activation, mitochondrial dysfunction, synaptic signaling, and calcium-related pathways, whereas PD subtypes showed divergence in neuroinflammatory, oxidative stress, and mitochondrial programs. Conclusions: We demonstrated stratification of AD and PD into molecular subtypes, potentially supporting scalable, mechanism-directed stratification and the development of future targeted, disease-modifying therapies. Full article

Background: The global number of individuals living with dementia is projected to rise from 57.4 million in 2019 to 152.8 million by 2050. Alongside this increase, the worldwide economic burden of dementia continues to grow, with the overall societal cost estimated at US$1313 billion in 2019—substantially higher than earlier projections. Objectives: To analyze the impact of dementia on long-term-care costs, we conducted a multivariate analysis to take into account overlaps with various other diseases. Methods: In this study, we conducted a multivariate analysis to assess the effect of major diseases on annual expenditure on long-term care by linking Japanese National Health Insurance and long-term-care insurance claims. Results: In a two-part analysis using a hurdle model, the first stage of multivariate logistic regression analysis of the presence or absence of disease showed that Parkinson’s disease had the highest multivariate-adjusted odds ratio, followed by Alzheimer’s disease and schizophrenia. In the second stage of the generalized linear model with log link–Gamma analysis of residents with positive costs, the disease with the highest exponential function (exp(b)) was Alzheimer’s disease, followed by stroke sequelae. Conclusions: To examine the impact of dementia on long-term-care costs, it is necessary to use multivariate analysis to avoid overlap with other diseases. Full article

Background: Global dementia policies advocate for early or timely diagnosis, yet evidence on benefits or harms remains limited. This systematic review evaluates quantitative evidence comparing outcomes of early versus late and timely versus untimely dementia diagnoses. Methods: Following PRISMA guidelines, the protocol was registered on PROSPERO. Comprehensive searches of PsycINFO, Medline, Embase, SCOPUS, and CINAHL were conducted without date restrictions. Eligible studies defined diagnostic timing and examined associations with outcomes for people with dementia and/or carers. Quality was appraised using the QuADS tool, and data were narratively synthesised. Results: Four studies (2018–2021) met inclusion criteria, encompassing 37,341 individuals with dementia and 1409 carers across Europe and the United States. Three studies investigated early versus late diagnosis; one assessed perceived timeliness. Definitions varied. Evidence of benefit was limited: one study reported a 9–23% reduction in mortality risk for early diagnosis. Another found that carers perceiving the diagnosis as untimely experienced greater and more persistent emotional distress. No significant associations were observed for cognitive or functional decline, hospitalisation, or emergency department attendance. Conclusions: Despite strong policy endorsement, empirical evidence on benefits of early or timely dementia diagnosis remains scarce, geographically narrow, and methodologically constrained. Future longitudinal studies explicitly defining diagnostic timing and incorporating psychosocial and contextual factors are needed to clarify potential benefits or harms for people with dementia and their carers. Full article

Introduction: Psychotic symptoms (PS) in Alzheimer’s disease (AD) are associated with unfavorable prognosis, including accelerated functional decline and reduced survival. Multiple neurotransmitter systems have been implicated in the pathophysiology of PS, with the serotonergic system emerging as particularly relevant. Materials and Methods: Between 2010 and 2020, 120 patients with prodromal AD and 26 cognitively healthy controls underwent comprehensive evaluation, including clinical history, neurological and neuropsychological assessment, neuroimaging, and lumbar puncture. All participants underwent longitudinal clinical monitoring for a minimum of five years or until the emergence of PS. In February 2024, baseline cerebrospinal fluid (CSF) serotonin (5-HT) concentrations were quantified using competitive ELISA (FineTest, Wuhan, China). Results: CSF 5-HT levels were significantly elevated (p < 0.003) in patients who subsequently developed psychosis (n = 49) compared with those who remained free of PS during the 8-year follow-up (n = 19). A threshold of 4.89 ng/mL yielded 80% sensitivity for identifying individuals at risk. Baseline Neuropsychiatric Inventory (NPI; p < 0.001) and Unified Parkinson’s Disease Rating Scale part III (UPDRS III; p < 0.009) scores also demonstrated strong discriminative capacity. Conclusions: Measurement of CSF 5-HT and detailed clinical profiling in prodromal AD may provide predictive value for psychosis onset within 8 years of diagnosis. To our knowledge, this is the first study to report CSF 5-HT findings in AD patients. Full article

Background: Older adults with Alzheimer’s Disease and Related Dementias (ADRD) experience a higher risk of falls. However, research lacks evidence on the effect of fall exposure on cognitive impairment and dementia. We investigated the association of falls and depressive symptoms with cognitive impairment and dementia in a nationally representative sample. Methods: We analyzed data from 6221 participants (age ≥ 65) in the Health and Retirement Study (HRS) from the 2018–2020 waves, using Multinomial logistic regression models. Measures included the HRS health status questionnaire, HRS cognition scale, and the Center for Epidemiological Studies Depression scale. Results: Prevalence of fall exposure across cognition levels was 44.61% for dementia, 37.76% for cognitive impairment, and 32.16% for normal cognition. Having at least one fall exposure in the last 24 months significantly increased odds of having dementia by 42%, while the relationship between fall exposure and cognitive impairment was non-significant. Depressive symptoms were also associated with cognitive impairment and dementia. The stratified analysis by residential areas revealed that having a fall exposure increased the likelihood of having cognitive impairment by 26% and dementia by 73% in urban residents. However, the association between fall exposure and cognitive outcomes was not significant in rural settings. Depressive symptoms increased the odds of cognitive impairment in both strata, with a larger effect size in rural settings (OR = 2.23, 95% CI [1.41, 3.54]). Conversely, the association between depressive symptoms and dementia was only significant in urban settings (OR = 3.20, 95% CI [1.99, 5.15]). Conclusions: Falls and depressive symptoms were significantly associated with the odds of cognitive impairment and dementia, with significant differential effects between rural and urban older adults. Full article

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects the daily lives of older adults, impacting their cognitive abilities as well as speech and language communication. Early detection is crucial, as it enables timely intervention and helps improve the quality of life for those affected. While large language models (LLMs) have shown promise from spontaneous speech, most studies are unimodal and miss complementary signals across modalities. Methods: We present an LLM-powered multimodal cross-attention framework that integrates lexical (text), acoustic (speech), and visual (image) information for dementia detection using the ADReSSo 2021 picture-description dataset. Within this framework, text data are encoded using the ModernBERT, audio features are extracted using the wav2vec 2.0-base-960, and the Cookie Theft image is represented through the CLIP ViT-L/14. These embeddings are linearly projected to a shared space and then combined via Transformer-based cross-attention, yielding a fused vector for AD detection. Results: Our results show that the trimodal model achieved the best overall performance when paired with an SVC classifier, reaching an accuracy of 0.8732 and an F1 score of 0.8571, surpassing both the top-performing unimodal and bimodal configurations. For interpretability, a sensitivity analysis of modality contributions reveals that text plays the primary role, audio provides complementary improvements, and image offers modest yet stabilizing contextual support. Conclusions: These results highlight that the method of multimodal embedding fusion significantly influences performance: a cross-attention block achieves an effective balance between accuracy and simplicity, producing integrated representations that align well with interpretable downstream classifiers. Full article

Background/Objectives: Dementia represents a complex syndrome in which biological, psychological, social, and cultural dimensions intersect. While its clinical features are well documented, less is known about how lived experiences, caregiving contexts, and cultural beliefs shape the trajectory of illness. This study explored clinical, behavioral, and socio-cultural dimensions related to the quality of life of people living with dementia from an anthropological perspective, focusing on the interaction between comorbidities, cognition, lifestyle, and caregiving environments as reported by their informal caregivers. Methods: We conducted a single-center, observational cross-sectional study including 73 family caregivers of patients with clinically diagnosed dementia who accessed care at the Neurology–Psychiatry Department of the C.F.2 Clinical Hospital (Bucharest, Romania) between November 2023 and April 2024. Caregivers provided socio-demographic, behavioral, lifestyle, and cultural information using a newly developed anthropological questionnaire. Descriptive and exploratory inferential analyses were performed to examine relationships between cognitive performance, comorbidities, lifestyle factors, and socio-cultural variables. Results: People with dementia had a mean age of 79.2 ± 7.5 years (range 66–95) and were predominantly female (71.2%). Multimorbidity was common, averaging 2.22 ± 1.03 chronic conditions, mainly neurological (84.9%) and cardiovascular (68.5%). The mean BMI was 26.1 ± 3.8 kg/m². Cognitive impairment was substantial (MMSE mean 11.47 ± 7), with descriptively lower scores among older individuals and those with lower education or income, although inferential tests were underpowered. Appetite and sleep disturbances were frequent and tended to co-occur with lower activity levels. Disclosure of diagnosis occurred in 74% of cases; reactions varied widely, ranging from acceptance to denial, confusion, anxiety, and sadness. Family responses likewise reflected a heterogeneous and often ambivalent adjustment process. Cultural beliefs and spirituality played a salient role in shaping explanatory models and coping strategies, with many caregivers attributing importance to religious practices and, to a lesser extent, alternative treatments. Conclusions: In this Romanian cohort, dementia was shaped not only by age-related multimorbidity and cognitive decline but also by caregiving practices, socioeconomic constraints and culturally grounded interpretations of illness. These findings highlight the relevance of integrative approaches to dementia care that consider medical, behavioral, and socio-cultural dimensions and that incorporate caregiver perspectives to improve the quality of life of both patients and families. Full article

Background/Objectives: People with advanced dementia experience difficulties in navigating, while wayfinding is essential for a level of autonomy. A properly designed building has the strength to facilitate this target group in wayfinding. While understanding their wayfinding needs and experiences, and the spatial characteristics (both facilitating and confusing) during the wayfinding process is crucial, this knowledge is still limited. This study mapped challenges that people with advanced dementia encounter on a route to an irregular destination in their familiar nursing home environment, specifically addressing confusing spatial characteristics. Methods: An observational study design with a mixed-method approach was applied. First, a navigation task was conducted to identify places of confusion on the way to the destination (n = 15 participants in four nursing homes). Affective states were captured by observations combined with biometric measurements. Second, both manual and space syntax floorplan analysis techniques were used to identify the spatial characteristics of potentially stressful spaces in nursing homes. Results: Nine participants reached the destination. The most observed wayfinding behaviors were looking at various things and stops on the route, and they were often accompanied by verbal navigational cues. Furthermore, most participants experienced some signs of stress or concentration. In total, eighteen confusing places in the nursing homes were identified. Conclusions: Regarding spatial characteristics supporting or hindering wayfinding skills for people with advanced dementia in nursing homes, this study confirmed some of the findings in the existing research (e.g., minimizing shifting directions for supporting wayfinding), contradicted the existing research (e.g., confusion arose at places with high visibility values), and added new findings (e.g., significantly widening corridors may be confusing). This study revealed that high-visibility areas and squares on the route confuse people with advanced dementia while wayfinding. Full article

Alzheimer’s disease (AD) is a leading form of dementia, marked by complex neuropathological features such as amyloid-β (Aβ) plaques and tau tangles. Recent research highlights the significant role of unmethylated cytosine–phosphate–guanine (CpG) motifs, short DNA sequences where a cytosine nucleotide is directly followed by a guanine nucleotide, linked by a phosphate group, in the disease’s development. CpG motifs, predominantly found in bacterial and mitochondrial DNA, can provoke immune responses when they appear in unexpected contexts. This review explores the intricate relationship between unmethylated CpG DNA and AD pathogenesis, investigating the mechanisms by which bacterial DNA enters the brain, activates immune pathways, and contributes to the progression of Alzheimer’s disease. Understanding these processes may offer new avenues for research and therapeutic intervention in AD. Full article

Eating behavior disturbances are increasingly recognized as clinically relevant features of dementias. Although underappreciated, such alterations affect nutritional status, metabolic state, and disease burden. Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) exhibit a wide range of manifestations in eating and appetite regulation. In behavioral variant frontotemporal dementia (bvFTD), hyperorality, increased appetite, preference for sweet and high-fat foods, altered table manners, and consumption of inedible objects are common and may appear early. In contrast, AD patients usually present with decreased appetite, early dysphagia, and weight loss, although increased appetite may also occur. Beyond clinical manifestations, this review synthesizes current evidence regarding the prevalence, metabolic and hormonal profiles, and neuroimaging patterns of eating behavior disturbances in FTLD and AD, provides insight into the complex underlying mechanisms causing these changes, and underlines the lack of clear treatment strategies in these cases. Full article

Background/Objective: To examine whether patients with late-onset schizophrenia (LOS) and very-late-onset schizophrenia-like psychosis (VLOS) are at a higher risk of developing dementia than patients with early-onset schizophrenia (EOS). Methods: A random sample of incident cases of patients with schizophrenia with an age of onset after age 40 (LOS) and age 60 (VLOS) was selected from a psychiatric case register covering all psychiatric services within the city of The Hague, The Netherlands, between 1997 and 2012. Schizophrenia diagnosis and age of onset were audited by systematic review of all case notes up to 2019. Patients who were initially misclassified as LOS/VLOS in the registry but, after this audit, had an age of onset before age 40, were classified as EOS. The risk of developing dementia was compared between the groups using a logistic regression model with correction for age, gender, and stroke as possible confounders. Results: Our study groups consisted of 74 patients with EOS, 81 with LOS, and 25 with VLOS. Dementia was present in 10 patients at follow-up, 7 out of 106 (6.6%) patients in the combined LOS and VLOS groups, and 3 out of 74 (4.1%) patients in the EOS group. However, after correction for confounders, logistic regression showed no statistically significant higher change in the development of dementia in LOS nor VLOS patients compared to EOS patients, nor with age of onset as a continuous variable. Conclusions: Patients with LOS and VLOS are not at a higher risk of developing dementia compared to patients with EOS. These results do not support the hypothesis that LOS and especially VLOS, are precursors of dementia. Full article

Background: International policy increasingly recognises the importance of inclusive, community-based support for people living with dementia. Football, as a culturally significant sport, has the potential to reach older adults and communities disproportionately affected by health inequalities. The objectives of this review were to collate evidence on football-based dementia initiatives, including intervention format, delivery approaches, and reported outcomes. Methods: Seven databases (Sportdiscus, MEDLINE, Embase, Scopus, PsycINFO, CINAHL, and Web of Science) were searched for relevant peer-reviewed and grey literature from their inception to June 2025. The PICO framework was used to define eligibility criteria. Eligible studies described community-based football-themed or football-based programmes involving people living with dementia. Data were extracted on participant sample, intervention characteristics, and reported outcomes, and iteratively charted. Results: In total, 11 of the 1059 identified articles were included within this review. Initiatives were often delivered through professional football clubs and charitable foundations, with formats ranging from reminiscence therapy sessions to walking football. Common outcomes for participants included increased sociability, improved mood, enhanced communication, and a strengthened sense of identity and belonging. Some interventions also reported physical benefits, such as improved mobility. Carers highlighted respite opportunities, peer support, and enjoyment from seeing relatives more engaged. Despite positive reports, outcome measurement was inconsistent, and most studies were small-scale or descriptive pilot projects. Conclusions: Football-based dementia initiatives provide meaningful, culturally grounded opportunities for social inclusion and support. Their delivery through community clubs/organisations positions them well to address inequities in dementia care, particularly in areas of disadvantage. However, stronger evaluation methods are required to build a robust evidence base and guide sustainable implementation at scale. Full article

Type 2 Diabetes Mellitus (T2DM) is a recognized risk factor for Alzheimer’s Disease (AD), as epidemiological research indicates that those with T2DM have a markedly increased risk of experiencing cognitive decline and dementia. Chronic hyperglycemia and insulin resistance in T2DM hinder cerebral glucose metabolism, reducing the primary energy source for neurons and compromising synaptic function. Insulin resistance impairs signaling pathways crucial for neuronal survival and plasticity, while high insulin levels compete with amyloid-β (Aβ) for breakdown by insulin-degrading enzyme, promoting Aβ buildup. Additionally, vascular issues linked to T2DM impair blood–brain barrier functionality, decrease cerebral blood flow, and worsen neuroinflammation. Elevated oxidative stress and advanced glycation end-products (AGEs) in diabetes exacerbate tau hyperphosphorylation and mitochondrial dysfunction, worsening neurodegeneration. Collectively, these processes create a robust biological connection between T2DM and AD, emphasizing the significance of metabolic regulation as a possible treatment approach for preventing or reducing cognitive decline. Here, we review the relationship between T2DM and AD and discuss the roles insulin, hyperglycemia, and inflammation therapeutic strategies have in successful development of AD therapies. Additionally evaluated are recent therapeutic advances, especially involving the polyflavonoid anthocyanin, against T2DM-mediated AD pathology. Full article