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J. Dement. Alzheimer's Dis., Volume 2, Issue 3 (September 2025) – 5 articles

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17 pages, 6011 KiB  
Article
Gray Matter Volume Associations with Montreal Cognitive Assessment Domains in an ADNI Cohort of Early-Onset Mild Cognitive Impairment and Alzheimer’s Disease
by Minos Kritikos, Taulant Rama, Vania Zubair, Chuan Huang, Christopher Christodoulou, Allen P. F. Chen, Roman Kotov, Frank D. Mann and on behalf of the Alzheimer’s Disease Neuroimaging Initiative
J. Dement. Alzheimer's Dis. 2025, 2(3), 24; https://doi.org/10.3390/jdad2030024 - 1 Jul 2025
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Abstract
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 [...] Read more.
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
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12 pages, 496 KiB  
Article
Comparison of Physical Activity Patterns Between Individuals with Early-Stage Alzheimer’s Disease and Cognitively Healthy Adults
by Léonie Moll, Michèle Häner, Roland Rössler and Sabine Krumm
J. Dement. Alzheimer's Dis. 2025, 2(3), 23; https://doi.org/10.3390/jdad2030023 - 1 Jul 2025
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Abstract
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 [...] Read more.
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
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9 pages, 199 KiB  
Article
Dilemmas in Implementing Advance Directives of Patients with Advanced Dementia
by Norman L. Cantor, William Choi and Michael J. Young
J. Dement. Alzheimer's Dis. 2025, 2(3), 22; https://doi.org/10.3390/jdad2030022 - 1 Jul 2025
Viewed by 478
Abstract
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 [...] Read more.
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
37 pages, 565 KiB  
Review
Outdoor-Based Care and Support Programs for Community-Dwelling People Living with Dementia and Their Care Partners: A Scoping Review
by Anthea Innes, Mason McLeod, Equity Burke, Dylan Lu, Constance Dupuis and Vanina Dal Bello-Haas
J. Dement. Alzheimer's Dis. 2025, 2(3), 21; https://doi.org/10.3390/jdad2030021 - 1 Jul 2025
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Abstract
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 [...] Read more.
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
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13 pages, 1483 KiB  
Article
Alzheimer’s Disease Lipidome: Elevated Cortical Levels of Glycerolipids in Subjects with Mild Cognitive Impairment (MCI) but Not in Non-Demented Alzheimer’s Neuropathology (NDAN) Subjects
by Paul L. Wood, John E. Cebak and Aaron W. Beger
J. Dement. Alzheimer's Dis. 2025, 2(3), 20; https://doi.org/10.3390/jdad2030020 - 1 Jul 2025
Viewed by 204
Abstract
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 [...] Read more.
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
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