J. Dement. Alzheimer's Dis., Volume 2, Issue 2 (June 2025) – 13 articles

Background: The Montreal Cognitive Assessment (MoCA) is widely used to evaluate global cognitive function; however, its precision in measurement in heterogeneous populations—especially among patients with Parkinson’s disease (PD)—remains underexplored. Methods: In this multicenter cross-sectional study, we examined the psychometric properties of the Brazilian Portuguese MoCA in 484 PD patients (age range, 26–90 years; mean ± SD, 59.9 ± 11.1 years; disease duration range, 1–35 years; mean ± SD, 8.7 ± 5.4 years) using Item Response Theory (IRT). The Graded Response Model (GRM) was employed to estimate item difficulty and discrimination parameters, and differential item functioning (DIF) concerning age and education was investigated via a Multiple Indicators Multiple Causes (MIMIC) model. Results: The MoCA demonstrated essential unidimensionality and robust model fit. GRM analyses revealed that items within the Attention and Naming domains had high discrimination, indicating sensitivity to subtle cognitive deficits, while Memory items exhibited lower discrimination. Orientation items showed low difficulty thresholds, suggesting a propensity for ceiling effects. The MIMIC model further indicated that age and education significantly influenced overall scores: increasing age was associated with lower performance, whereas higher educational attainment correlated with better outcomes, particularly in Memory Recall and Executive/Visuospatial domains, even after accounting for their modest inverse relationship. Conclusions: Our findings support the validity of the Brazilian Portuguese MoCA for cognitive screening in PD while highlighting item-level biases linked to age and education. These results advocate for using education-adjusted norms and computerized scoring algorithms that incorporate item parameters, ultimately enhancing the reliability and fairness of cognitive assessments in diverse clinical populations. Full article

Background: The timely detection of cognitive decline in highly educated adults is challenging due to their resilient cognitive abilities and the limited sensitivity of neuropsychological tests for this group. Therefore, evaluating subjective facets such as subjective cognitive decline (SCD) becomes imperative, potentially enabling the early identification of cognitive decline. Objective: Our primary objective was to identify effective methods, both objective and subjective, for the early detection of cognitive decline in highly educated older adults. A secondary objective was to translate and validate a Hebrew adaptation of the SCD questionnaire. Methods: Initially (T0), the study included 28 highly educated participants (mean age = 72.6, SD = 4.54; mean education 17.6, SD = 3.41). By the final evaluation (T7), 20 participants remained. Annual assessments involved objective neuropsychological tests and self-report questionnaires evaluating depression, anxiety, and SCD with changes analyzed over time using repeated measures ANOVA. Results: Significant declines were observed in the following objective neuropsychological tests: Rey–Osterrieth Complex Figure Test (ROCFT) copy, F(3,57) = 9.05, p < 0.001, ηp2 = 0.32, and Rey Auditory Verbal Learning Test (RAVLT) trial six, F(1,19) = 7.32, p < 0.05, ηp2 = 0.28, which is consistent with previous findings. The Hebrew SCD questionnaire demonstrated high reliability and validity and was highly correlated with cognitive decline. Conclusions: The ROCFT copy and the Hebrew SCD questionnaire can serve as valuable indicators for the early detection of cognitive decline in highly educated older adults. Full article

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss. Increasing evidence highlights oxidative stress as a pivotal contributor to AD pathogenesis, closely associated with hallmark features such as amyloid-β (Aβ) plaque accumulation, tau hyperphosphorylation, and synaptic dysfunction. This review aims to elucidate the mechanisms by which oxidative stress contributes to AD and to evaluate emerging therapeutic strategies targeting oxidative damage. Methods: We conducted an extensive literature search using PubMed and Google Scholar for studies published between 1994 and 2024. This narrative review integrates findings from in vitro, in vivo, and clinical studies focusing on oxidative stress, mitochondrial dysfunction, and their roles in AD to provide a comprehensive overview of the current research landscape. Results: ROS and RNS levels are significantly elevated in aging and AD-affected brains, leading to oxidative damage to lipids, proteins, and DNA, which compromises neuronal function and structure. Mitochondrial dysfunction plays a key role by amplifying ROS production, impairing ATP synthesis, and accelerating neurodegeneration. Oxidative stress also interacts with central AD pathologies, including Aβ aggregation, tau hyperphosphorylation, and synaptic dysfunction, creating a vicious cycle of neuronal injury. Although traditional antioxidant therapies have shown limited efficacy in clinical settings, often due to poor bioavailability, limited BBB penetration, and systemic distribution, novel strategies such as mitochondrial-targeted antioxidants and combination therapies have demonstrated improved outcomes in preclinical models. Conclusions: Oxidative stress plays a multifaceted role in the progression of AD, necessitating comprehensive therapeutic approaches. Future treatments should focus on targeting multiple aspects of oxidative stress, particularly mitochondrial dysfunction, to enhance clinical outcomes and slow neurodegeneration in AD patients. Full article

Background/Objectives: Subjective cognitive decline (SCD) is a common symptom experienced by individuals in the preclinical stage of dementia. However, traditional neuropsychological tests often fail to detect subtle cognitive changes associated with SCD. People with SCD may appear to have intact cognitive function (as measured by traditional tests), but they themselves subjectively feel that their cognition is becoming impaired. Methods: This preliminary study investigated the relationship between SCD and antisaccade performance as a potential early marker of dementia risk in a community-based sample of older adults (N = 17, mean age = 77.71 years). SCD was also explored by calculating the dissociation between objective and subjective memory performance, with SCD implied if there was a large dissociation between perceived memory performance but intact objective performance. Results: Participants with evidence of SCD exhibited significantly increased antisaccade latency compared to healthy controls, even when standard cognitive tests were normal. Antisaccade latency showed a significant correlation with self-reported cognitive complaints (r = 0.57, p = 0.018), while traditional cognitive measures did not. Conclusions: These compelling but preliminary findings suggest that antisaccade performance may be a more sensitive indicator of early cognitive decline than traditional cognitive measures, even in the preclinical stage of dementia. The results have implications for early dementia diagnosis, as antisaccade tasks could be incorporated into routine assessments to identify individuals at risk for dementia, potentially enabling earlier therapeutic intervention. Full article

Alzheimer’s disease (AD) is characterized by the progressive loss of cognitive function and is frequently accompanied by neuropsychiatric symptoms (NPS). Pathologically, AD is defined by two hallmark features: the extracellular accumulation of β-amyloid and the intracellular hyperphosphorylation of the tau protein. In addition to these primary changes, several other abnormalities are associated with the disease, including neuroinflammation, synaptic loss, oxidative stress, neurotransmitter imbalance, and genetic and epigenetic alterations. NPS in AD encompass a range of symptoms, such as anxiety, apathy, agitation, depression, and psychosis. These symptoms are thought to arise partly from the damage caused by the pathological hallmarks of AD, which impair various neurotransmitter systems. Altered levels of several neurotransmitters, including gamma-aminobutyric acid (GABA), serotonin (5-HT), dopamine (DA), and the cholinergic and noradrenergic systems, have been implicated in the development of agitation. Additionally, reduced endocannabinoid system (ECS) functionality, particularly cannabinoid receptor 1 (CB1R), has been linked to neurobehavioral alterations. Preclinical studies suggest that a decrease in CB1R levels is associated with aggressive behavior, and CB1R agonists have demonstrated beneficial effects in alleviating agitation and related symptoms. Given these findings, the current review focuses on the therapeutic potential of targeting neurotransmitter systems and CB1R dysfunction to manage agitation in AD. Full article

Background/Objectives: This article addresses an exploratory design study in the framework of the REMIND research study, which is focused on the importance of cultural and biographical components for the cognitive and sensory stimulation of persons with dementia. Through a case study conducted at a Day Centre from the Alzheimer Portugal association, it aims to demonstrate the relevance of including cultural elements in sensory stimulation artefacts for persons with dementia. It is hypothesised that the inclusion of cultural elements central to the biographical stories of these persons will have greater potential to stimulate their senses and reminiscences. In the context of this study, this hypothesis was explored through textile artefacts. Methods: Methods included participant observation, sensory and visual ethnography, interviews, focus groups, and a participatory design approach involving women with moderate and advanced Alzheimer’s disease and health professionals. Due to the severely compromised verbal communication abilities of some of the women, beyond-verbal communication strategies were adopted. Results: The results showed that textiles with a cultural presence tended to elicit greater reactions and reminiscences of events associated with the women’s life stories. Crochet artefacts were of particular relevance: women’s involvement in activities with crochet artefacts was substantially higher and, in certain cases of women with moderate dementia, these artefacts activated positive memories of the person, suggesting the potential of crochet for sensory stimulation. Conclusions: The results support the hypothesis; however, further research exploring other cultural elements and involving a broader demographic is needed. Based on the results obtained, a sensory blanket was developed, which is already in use at the Centre. Full article

Introduction—Aim: Agitation and aggression are common symptoms in people with Alzheimer’s disease and other dementias. This systematic review outlines the current evidence for the effect of antidementia treatments on agitation and aggression in patients with Alzheimer’s disease. Methods: The literature search was performed by manually checking articles published since 2000 in the following databases: PubMed, ResearchGate, and Google Scholar, following the PRISMA guidelines. Results: Nineteen double blinded placebo-controlled trials were included. Treatment with galantamine seems to provide more credible evidence for treating or preventing agitation/aggression. Studies on memantine often presented with an improvement of the neuropsychiatric inventory but not specifically on agitation/aggression. The trials on donepezil and rivastigmine either did not include enough information on agitation/aggression or did not provide compelling results. The incidence of agitation as an adverse event was not higher in antidementia treatments compared to placebo. Conclusions: Agitation and aggression are common symptoms of Alzheimer’s disease and have a significant impact on the patient, caregiver, and the broader healthcare system. The current literature lacks robust evidence on which of the antidementia treatments could be used to manage or prevent agitation and aggression in Alzheimer’s disease. In most included studies, no specific scores that assess those symptoms were used. Future research that specifically focuses on different disease phenotypes and behavioral profiles to enhance and facilitate the management of these symptoms is needed. Full article

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that disrupts functional brain connectivity, leading to cognitive and functional decline. Electroencephalography (EEG), a noninvasive and cost-effective technique, has gained attention as a promising tool for studying brain network alterations in AD. This study aims to leverage EEG-derived connectivity metrics to differentiate between healthy controls (HC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD, offering insights into disease progression. Methods: Using graph theory-based analysis, we extracted key connectivity metrics from resting-state EEG signals, focusing on the betweenness centrality and clustering coefficient. Statistical analysis was conducted across multiple EEG frequency bands, and discriminant analysis was applied to evaluate the classification performance of connectivity metrics. Results: Our findings revealed a progressive increase in theta-band betweenness centrality and a concurrent decrease in alpha- and beta-band centrality, reflecting AD-related network reorganization. Among the examined metrics, theta-band betweenness centrality exhibited the highest discriminative power in distinguishing AD stages. Additionally, classification performance using connectivity metrics was comparable to advanced deep learning models, highlighting their potential as predictive biomarkers. Conclusions: EEG-derived connectivity metrics demonstrate strong potential as noninvasive biomarkers for the early detection and monitoring of AD progression. Their effectiveness in capturing network alterations underscores their value in clinical diagnostic workflows, offering a scalable and interpretable alternative to deep learning-based models for AD classification. Full article

Background/Objectives: Sex differences in the relationship between subjective cognitive decline (SCD) and health-related quality of life (HRQOL), as well as psychological and physical factors affecting this relationship, have not been fully investigated. In this study, we aimed to examine the relationship between SCD severity and HRQOL in community-dwelling older adults in Japan and to clarify the psychological and physical factors affecting this relationship by sex. Methods: This cross-sectional study included 456 community-dwelling older adults and was conducted in September 2024. SCD severity was evaluated using the visual analog scale, and HRQOL was assessed using the EuroQol 5-Dimensions 5-Levels. Psychological factors (depression and insomnia) and physical factors (pain and frailty) were measured, and the relationship between SCD and HRQOL was analyzed by sex. Results: In women, HRQOL decreased as SCD severity increased and was associated with depression, insomnia, and physical pain. Conversely, in men, the association between SCD and HRQOL was not significant, and HRQOL was mainly associated with physical health factors, including pain and frailty. Conclusions: There were sex differences in the relationship between SCD and HRQOL, with women’s awareness of SCD associated with a decline in HRQOL, whereas physical health was the main determinant in men. Sex-specific interventions with psychological support being effective for women and support focusing on maintaining physical health for men are warranted. Full article

Background/Objective: Cyclosporine A and other calcineurin inhibitors have been identified as prospective treatments for preventing Alzheimer’s disease. We previously found that calcineurin inhibitors elicit a unique behavioral profile in zebrafish larvae, characterized by increased activity, acoustic hyperexcitability, and reduced visually guided behaviors. Screening a large library of FDA-approved compounds using Z-LaP Tracker revealed that some heart medications produce a similar behavioral profile, suggesting these drugs may exert calcineurin-inhibitor-like effects relevant to prevent-ing or ameliorating Alzheimer’s disease. Methods: Screening a large library of FDA-approved drugs using Z-LaP Tracker, a neural network model, revealed a cluster of 65 drugs demonstrating a cyclosporine A-like behavioral profile. Fourteen of these drugs were heart medications, including angiotensin receptor blockers, beta blockers, al-pha-adrenergic receptor antagonists, and a statin. Results: Dual administration of the heart medications with cyclosporine A in Z-LaP Tracker revealed synergistic effects: lower doses of each heart medication could be delivered in conjunction with a lower dose of cyclosporine A to evoke a similar or larger behavioral effect than higher doses of each drug independently. Other studies have shown that many of these heart medica-tions drugs directly or indirectly inhibit the calcineurin–NFAT pathway, like cyclo-sporine A, providing a potential mechanism. Conclusions: Co-administering a low dose of cyclosporine A with select cardiac drugs could be a potentially effective treatment strategy for preventing Alzheimer’s disease occurrence and simultaneously treating cardiovascular dysfunction, while mitigating the side effects associated with higher doses of cyclosporine A. Given that heart disease precedes Alzheimer’s disease in many patients, physicians may be able to create a treatment regimen that addresses both con-ditions. Our results suggest that a calcineurin inhibitor combined with simvastatin, irbesartan, cilostazol, doxazosin, or nebivolol is the most promising candidate for future exploration. Full article

Background: Sex differences in the association of cognitive function and imaging measures with dementia have not been fully investigated. Understanding sex differences in the dementia-related socioeconomic, cognitive, and imaging measurements is crucial for uncovering sex-related pathways to dementia and facilitating early diagnosis, family planning, and cost control. Methods: We selected data from the Open Access Series of Imaging Studies, with longitudinal measurements of brain volumes, on 150 individuals aged 60 to 96 years. Dementia status was determined using the Clinical Dementia Rating (CDR) scale, and Alzheimer’s disease was diagnosed as a CDR of ≥0.5. Generalized estimating equation models were used to estimate the associations of socioeconomic, cognitive, and imaging factors with dementia in men and women. Results: The study sample consisted of 88 women (58.7%) and 62 men (41.3%), and the average age of the subjects was 75.4 years at the initial visit. A lower socioeconomic status was associated with a reduced estimated total intracranial volume in men, but not in women. Ageing and lower MMSE scores were associated with a reduced nWBV in both men and women. Lower education affected dementia more in women than in men. Age, education, Mini-Mental State Examination (MMSE), and normalized whole-brain volume (nWBV) were associated with dementia in women, while only MMSE and nWBV were associated with dementia in men. Conclusions: The association between education and the prevalence of dementia differs in men and women. Women may have more risk factors for dementia than men. Full article

Background: Dementia patients often experience a decline in both their cognitive and sensory functions, particularly hearing, which significantly impacts their quality of life. This study evaluates the effectiveness of a combined Digital Cognitive Stimulation Therapy (DKST) and online hearing training intervention in enhancing the quality of life of individuals with dementia. Methods: Twenty-three patients participated in a six-month program integrating cognitive exercises and hearing rehabilitation, facilitated by trained co-therapists. Quality of life was assessed using the Quality of Life (QoL) Questionnaire, while the Mini-Mental State Examination (MMSE) was employed to categorize participants based on their cognitive status. Results: The results revealed significant improvements in the overall quality of life. Conclusions: This study demonstrates that combining DKST with hearing training effectively addresses sensory and cognitive challenges, supporting improved quality of life and highlighting the potential of digital interventions in dementia care. Full article

Background/Objectives: The aging population presents significant challenges to healthcare systems, with conditions like dementia severely affecting the quality of life for older adults, especially those in long-term care. Gamification has the potential to motivate older adults to engage in exercise by transforming physical activities into enjoyable experiences. Incorporating gaming elements in cycling exercises can foster a sense of interest and achievement, potentially improving health outcomes. This pilot study aims to explore interdisciplinary staff perspectives on using a digital game to motivate cycling exercise among residents living with dementia in long-term care (LTC). Methods: This study applied a qualitative description design. Using an interpretive description approach, we conducted focus groups with 29 staff members, including recreational therapists, rehabilitation therapists, nurses, care aides, and leadership in an LTC home. The consolidated framework for implementation research (CFIR) guided the data analysis to identify barriers and facilitators to adopting the digital game. Results: Engaging LTC residents living with dementia presents various challenges. Identified potential barriers to implementing the cycling game include cognitive and physical limitations, resistance to change, and intervention complexity. Frontline staff strategies include flexible invitations, social groups, making it fun, and building rapport. Success relies heavily on its cultural and individual relevance, along with strong support from leadership, peers, and family. Conclusions: This pilot study explored staff perspectives on the potential integration of a gamified cycling intervention for older adults with dementia in long-term care settings. Staff emphasized that successful implementation would depend on addressing key barriers and identifying enabling strategies. Based on these findings, practice implications were provided to support effective integration. Further research, including resident input and long-term evaluations, is needed to assess the feasibility, acceptance, and effectiveness of gamification in promoting health outcomes for this population. This study adhered to the COREQ Checklist. Full article