Search Results (33)

The transgenic animals have been yielding invaluable insights into amyloid pathology by replicating the key features of Alzheimer’s disease (AD). However, there is no clear relationship between senile plaques and memory deficits. Instead, cognitive impairment and synaptic dysfunction are particularly linked to a rise in Aβ_1-42 oligomer level. Thus, injection of Aβ_1-42 oligomers into a specific brain region is considered an alternative approach to investigate the effects of increased soluble Aβ species without any plaques, offering higher controllability, credibility and validity compared to the transgenic model. The hippocampal CA1 (cornu ammonis 1) region is selectively affected in the early stage of AD and specific targeting of CA1 region directly links Aβ oligomer-related pathology with memory impairment in early AD. Next, the inhibitory avoidance (IA) task, a learning paradigm to assess the synaptic basis of CA1-dependent contextual learning, triggers training-dependent synaptic plasticity similar to in vitro HFS (high-frequency stimulation). Given its reliability in assessing contextual memory and synaptic plasticity, this task provides an effective framework for studying early stage AD-related memory deficit. Therefore, in this review, we will focus on why Aβ_1-42 oligomer injection is a valid in vivo model to investigate the early stage of AD and why dorsal CA1 region serves as a target area to understand the adverse effects of Aβ_1-42 oligomers on contextual learning through the IA task. Full article

Background/Objectives: T1-weighted magnetic resonance imaging (MRI) and the Montreal Cognitive Assessment are standard, efficient, and swift clinical and research tools used when interrogating cognitively impairing (CI) conditions, such as Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD). However, the associations between gross cognitive impairment (CI) as compared to domain-specific functioning and underlying neuroanatomical correlates have not been investigated among individuals with early-onset Mild Cognitive Impairment (MCI) or Alzheimer’s disease (EOAD), who can benefit greatly from early diagnosis and intervention strategies. Methods: We analyzed T1-weighted MRIs and Montreal Cognitive Assessment (MoCA) scores from the ADNI database in individuals < 65 years old who were either cognitively normal (CN) or had MCI or EOAD. Gray matter volume (GMV) was estimated in voxel-based morphometry (VBM) and ROI-parcellation general linear models examining associations with individual MoCA scores after adjusting for demographic covariates. Results: Results from 120 subjects (44 CN, 62 MCI, and 14 EOAD), identified significant global but also individually distinct domain-specific topographical signatures spanning the temporal, parietal, limbic, occipital, frontal lobes, and cingulate gyri. Conclusions: The results highlight neural correlates of cognitive functioning in a sample of young patients representative of the AD continuum, in addition to studying the structural MRI and functional cognitive difference. Full article

Background: Physical activity (PA) has been shown to prevent Alzheimer’s disease (AD) by reducing amyloid accumulation, lowering inflammatory factors, and increasing hippocampal grey matter. While high lifetime PA engagement is associated with a reduced risk of AD, the relationship between specific types of PA and early-stage AD remains unclear. As AD primarily affects cognitive function before physical capabilities, PA engagement—an important factor in PA—needs further investigation. Objectives: This study explores the potential association between current participation in open-skill sports (OSSs) versus closed-skill sports (CSSs) and early-stage AD. Methods: The sample (N = 128) included a cognitively healthy (HC, n = 78) group and an Alzheimer’s disease (AD) group, combining amnestic mild cognitive impairment due to AD patients (n = 22) and early-stage Alzheimer’s dementia patients (n = 28), reflecting the continuum of progression from aMCI to dAD (n = 50). PA was assessed with the Physical Activity Scale for the Elderly questionnaire, specifically focusing on PA within the last seven days. The statistical analyses included Mann–Whitney U tests and backwards stepwise logistic regression models. Results: Key predictors of group classification (AD vs. NC) included sex, high frequency of PA, and high duration of PA, each for the last seven days. Participation in OSS was significantly associated with medium PA frequency, high PA duration, both within the last seven days, and age, but not with diagnostic status. No statistically significant differences in PA levels (OSSs or CSSs) executed within the last seven days were observed between the AD and HC groups. Conclusions: Participation in OSSs or CSSs within the last seven days was only a marginally significant predictor of AD vs. HC status, and a diagnosis of AD was not predictive of OSS participation within the last seven days. Given the protective role of PA in AD, future research should aim to identify specific PA types that effectively support cognitive health in older adults with early cognitive decline. Full article

Background/Objectives: To avoid becoming mired in prolonged deep dementia, some people seek to hasten death by advance instructions rejecting life-sustaining medical intervention (LSMI) at a point of cognitive decline they define in advance as unacceptable. When the time comes to implement such advance instructions and to allow the person in advanced dementia to die, many clinicians experience moral and ethical qualms. The decision makers face a clash between people’s legally recognized self-determination prerogative to control their post-competence medical fate and the decision makers’ conviction that humane treatment dictates sustaining the well-being, i.e., the physical “best interests,” of the patient who no longer recalls prior instructions grounded in concerns about personal dignity. The authors’ objective here is to provide guidance in resolving this anguishing dilemma confronting medical decision makers. Methods: The authors construct and analyze a case scenario involving a patient in a state of advanced dementia with a clear advance instruction rejecting LSMI at the current point of debilitation, but who is not ostensibly suffering, is experiencing a modicum of life satisfaction, and is making life-affirming utterances. The two lead authors present contrasting views on whether legal and moral factors impel the implementation of the advance directive rejecting treatment or rather dictate life-sustaining medical intervention. Results: At this early stage of jurisprudence involving persons in advanced dementia, there can be no definitive resolution of the difficult legal/moral clash confronting decision makers. Some sources would conclude that persons are legally entitled to define precipitous mental decline and complete dependence on others as intolerably undignified and inconsistent with their self-defined life narrative. Other sources would be guided by humane respect for the contemporary well-being of a non-suffering patient, especially one making life-affirming utterances. Conclusion: Through the lens of this illuminating case and contrasting analyses, readers should better understand how clinicians should weigh advance directives against shifting care preferences subsequently articulated by persons with advanced dementia. Full article

Background/Objectives: How to best assist people living with dementia (PLWD) and their care partners to maximize quality of life and quality of living, through appropriate and effective non-pharmaceutical approaches, remains a focus of dementia societies and organizations worldwide. This scoping review explored the types, opportunities, benefits and challenges of outdoor-based care and support programs for community-dwelling PLWD and their care partners. Methods: The methodological framework proposed by Arksey & O’Malley (2005) and modified by Levac et al. (2010) was followed. Four research databases were searched from January 2000 to November 2024; 2817 articles were retrieved and 20 met inclusion criteria and underwent data extraction. Results: Program types included the following: nature-based, care farm, green care farm, and farm-based dementia care programs, representing more than half of the included articles; health walks; and outdoor horticulture/garden/gardening programs. The number of PLWD participants ranged from 4 to 136. The total number of care partner participants was 151 and the total number of service provider participants was 87. The essence of, and connections with, nature and the outdoors had notable relevance and value for PLWD. Reported benefits, assessed quantitatively and qualitatively, were numerous and those in the social domain were reported most often. Identified challenges and barriers were related to risks and safety and program development, and implementation and delivery. Conclusions: The noteworthy potential of outdoor-based care and support programs to promote and enhance the quality of life and quality of living of community-dwelling PLWD and their care partners was elucidated. As most PLWD prefer to, and do, continue to reside in their homes, including those with advancing symptoms, the findings have significant relevance and implications for real-world practice and policy. Future research addressing current gaps will strengthen this growing field of dementia research. Full article

Background/Objectives: Abnormal brain glycerolipid metabolism has been reported for Alzheimer’s disease (AD). This includes both diacylglycerols (DGs) and monogalactosyl-DGs (MGDGs), which are elevated in AD subjects. While DGs are also elevated in subjects with mild cognitive impairment (MCI), MGDGs have not yet been examined at this early stage of cognitive impairment. Methods: MGDG, triacylglycerol (TG), and ether glycerolipid levels in the cerebral cortex gray matter of controls, MCI, and non-demented Alzheimer’s neuropathology (NDAN) subjects were monitored by high-resolution mass spectrometry (<2 ppm mass error). Results: MGDG, MGDG ether, DG ether, and TG levels were elevated in the cerebral cortex of MCI but not NDAN subjects. Conclusions: A diverse array of glycerolipids was elevated in MCI subjects, suggesting a role in cognitive dysfunction. This suggestion is further supported by the maintenance of normal glycerolipid levels in NDAN subjects with amyloid accumulation but not cognitive deficits. Our data clearly indicate that while complex lipid alterations occur in MCI subjects, relative to controls 20 years younger, no such lipid alterations occur in NDAN subjects. While amyloid deposition in MCI is not involved in the observed lipid alterations, other ongoing neuropathologies may contribute to changes in lipid dynamics and vice versa. Full article

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