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The Journal of Alzheimer’s Disease is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer’s disease.
The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. The journal is dedicated to providing an open forum for original research that will expedite our fundamental understanding of Alzheimer’s disease.
Authors: Jehu, Deborah A. | Pottayil, Faheem | Dong, Yanbin | Zhu, Haidong | Sams, Richard | Young, Lufei
Article Type: Research Article
Abstract: Background: Physical activity preserves cognitive function in people without dementia, but the relationship between physical activity and cognitive domains among people living with dementia is unclear. Objective: The objective of this study was to explore the association between physical activity and cognition domains among people living with dementia. Methods: Participants living with dementia in residential care facilities (complete case analysis: n = 24/42) completed a battery of cognitive tests (global cognition : Montreal Cognitive Assessment; executive function : Trail-Making Test, Digit Span Forward Test; perception and orientation : Benton Judgement of Line Orientation Test; …language : Boston Naming Test; learning and memory : Rey Auditory Verbal Learning Test; complex attention : Digit Symbol Substitution Test). Participants wore an actigraphy monitor on their non-dominant wrist over seven days. We conducted a linear regression for total physical activity (independent variable) with race (white/black), fall risk (Morse Fall Scale), and the number of comorbidities (Functional Comorbidities Index) as covariates, and cognitive tests as variables of interest. Results: Participants were primarily male (75%), white (87.5%), and 50%had unspecified dementia (Alzheimer’s disease: 33%). Greater physical activity was associated with poorer global cognition, better executive function, and better learning and memory (p s < 0.05). Physical activity was not related to visuospatial perception, language, or complex attention. Conclusions: Physical activity may preserve executive function and learning and memory among people living with dementia. Wandering is more common in later stages of dementia, which may explain greater physical activity observed with lower global cognition. Regularly assessing physical activity may be useful in screening and monitoring cognitive changes. Show more
Keywords: Accelerometry, actigraphy, Alzheimer’s disease, cognition, cognitive domains, dementia, physical activity
DOI: 10.3233/JAD-230594
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2024
Authors: Toya, Shunji | Hashimoto, Mamoru | Manabe, Yuta | Yamakage, Hajime | Ikeda, Manabu
Article Type: Research Article
Abstract: Background: Quality of life (QOL) and treatment needs of patients with dementia with Lewy bodies (DLB) and their caregivers are important factors to consider when developing treatment strategies. Objective: To investigate factors associated with QOL in patients with DLB, and to examine factors associated with activities of daily living (ADL) if ADL was associated with QOL. Methods: We previously conducted a questionnaire survey study to investigate the treatment needs of patients with DLB and their caregivers. This pre-specified additional analysis evaluated the Physical Component Score (PCS) and Mental Component Score (MCS) of the Short Form-8 for …QOL, and the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II total score for ADL. Results: In total, 231 patient– caregiver pairs and 38 physicians were included. Multivariable analysis of QOL showed that the MDS-UPDRS Part II total score (standard regression coefficient [β], – 0.432) was associated with the PCS, and presence of depression (β, – 0.330) was associated with the MCS. The severity of postural instability/gait disorder (PIGD) (β, 0.337) and rigidity (β, 0.266), presence of hallucinations (β, 0.165), male sex (β, 0.157), and use of “short stay” or “small-scale, multifunctional home care” (β, 0.156) were associated with worsened ADL. Conclusions: In patients with DLB, QOL was negatively impacted by severity of ADL disability and depression, and ADL was negatively impacted by severity of PIGD and rigidity, hallucinations, male sex, and use of “short stay” or “small-scale, multifunctional home care.” Show more
Keywords: Activities of daily living, Alzheimer’s disease, cross-sectional studies, dementia, depression, hallucinations, Lewy body, parkinsonism, quality of life
DOI: 10.3233/JAD-231302
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2024
Authors: Desai, Shivum | Chen, Ivy Y. | Hom, Christy | Doran, Eric | Nguyen, Dana D. | Benca, Ruth M. | Lott, Ira T. | Mander, Bryce A.
Article Type: Research Article
Abstract: Background: While obstructive sleep apnea (OSA) and insomnia symptoms in neurotypical populations are associated with Alzheimer’s disease (AD), their association with dementia in adults with Down syndrome (DS) remains less clear, even though these symptoms are prevalent and treatable in DS. Understanding their associations with AD-related dementia status, cognitive impairment, and functional deterioration may lead to interventions to slow decline or disease progression in adults with DS. Objective: To characterize differences in OSA and insomnia symptom expression by dementia status, and to determine which sleep factors support dementia diagnosis. Methods: Multimodal consensus conference was used to …determine dementia status in 52 adults with DS (52.2 ± 6.4 years, 21 women). Cognitive impairment, adaptive behavior skills, and symptoms of OSA and insomnia were quantified using validated assessments for adults with DS and their primary informants. Results: A sex by dementia status interaction demonstrated that older women with DS and dementia had more severe terminal insomnia but not OSA symptoms relative to older women with DS who were cognitively stable (CS). Greater insomnia symptom severity was associated with greater functional impairments in social and self-care domains adjusting for age, sex, premorbid intellectual impairment, and dementia status. Conclusions: Insomnia symptoms are more severe in women with DS with dementia than in women with DS and no dementia, and regardless of dementia status or sex, more severe insomnia symptoms are associated with greater impairment in activities of daily living. These findings underscore the potential importance of early insomnia symptom evaluation and treatment in women with DS at risk of developing AD. Show more
Keywords: Activities of daily living, Alzheimer’s disease, dementia, disorders of excessive somnolence, Down syndrome, sleep, sleep apnea syndromes, sleep initiation and maintenance disorders
DOI: 10.3233/JAD-220750
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-17, 2024
Authors: Caballero, H. Sebastian | McFall, G. Peggy | Gee, Myrlene | MacDonald, Stuart | Phillips, Natalie A. | Fogarty, Jennifer | Montero-Odasso, Manuel | Camicioli, Richard | Dixon, Roger A.
Article Type: Research Article
Abstract: Background: Alzheimer’s disease (AD) and Lewy body disease (LBD) are characterized by early and gradual worsening perturbations in speeded cognitive responses. Objective: Using simple and choice reaction time tasks, we compared two indicators of cognitive speed within and across the AD and LBD spectra: mean rate (average reaction time across trials) and inconsistency (within person variability). Methods: The AD spectrum cohorts included subjective cognitive impairment (SCI, n = 28), mild cognitive impairment (MCI, n = 121), and AD (n = 45) participants. The LBD spectrum included Parkinson’s disease (PD, n = 32), mild cognitive impairment in PD (PD-MCI, n = 21), …and LBD (n = 18) participants. A cognitively unimpaired (CU, n = 39) cohort served as common benchmark. We conducted multivariate analyses of variance and discrimination analyses. Results: Within the AD spectrum, the AD cohort was slower and more inconsistent than the CU, SCI, and MCI cohorts. The MCI cohort was slower than the CU cohort. Within the LBD spectrum, the LBD cohort was slower and more inconsistent than the CU, PD, and PD-MCI cohorts. The PD-MCI cohort was slower than the CU and PD cohorts. In cross-spectra (corresponding cohort) comparisons, the LBD cohort was slower and more inconsistent than the AD cohort. The PD-MCI cohort was slower than the MCI cohort. Discrimination analyses clarified the group difference patterns. Conclusions: For both speed tasks, mean rate and inconsistency demonstrated similar sensitivity to spectra-related comparisons. Both dementia cohorts were slower and more inconsistent than each of their respective non-dementia cohorts. Show more
Keywords: Alzheimer’s disease, Canadian consortium on neurodegeneration in aging (CCNA), cognitive speed, COMPASS-ND study, inconsistency, Lewy body disease, mean rate, reaction time
DOI: 10.3233/JAD-240210
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-23, 2024
Authors: Chen, Xi | Walton, Karen | Brodaty, Henry | Chalton, Karen
Article Type: Review Article
Abstract: Cellular senescence, a hallmark of aging, plays an important role in age-related conditions among older adults. Targeting senescent cells and its phenotype may provide a promising strategy to delay the onset or progression of Alzheimer’s disease (AD). In this review article, we investigated efficacy and safety of nutrition senotherapy in AD, with a focus on the role of polyphenols as current and potential nutrition senotherapeutic agents, as well as relevant dietary patterns. Promising results with neuroprotective effects of senotherapeutic agents such as quercetin, resveratrol, Epigallocatechin-gallate, curcumin and fisetin were reported from preclinical studies. However, in-human trials remain limited, and findings …were inconclusive. In future, nutrition senotherapeutic agents should be studied both individually and within dietary patterns, through the perspective of cellular senescence and AD. Further studies are warranted to investigate bioavailability, dosing regimen, long term effects of nutrition senotherapy and provide better understanding of the underlying mechanisms. Collaboration between researchers needs to be established, and methodological limitations of current studies should be addressed. Show more
Keywords: Alzheimer’s disease, cellular senescence, cognition, mild cognitive impairment, nutrition senotherapeutics, senolytic agent
DOI: 10.3233/JAD-231222
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-23, 2024
Authors: Lee, Cecilia S. | Ferguson, Alina N. | Gibbons, Laura E. | Walker, Rod | Su, Yu-Ru | Krakauer, Chloe | Brush, Michael | Kam, Jason | Larson, Eric B. | Arterburn, David E. | Crane, Paul K. | Takahashi, Missy | Zhang, Yi | Jiang, Yu | Wu, Yue | Cooper, Julie | Pope, Beth | Blazes, Marian | Lee, Aaron Y. | Lee, Michael L. | Wang, Ruikang | Cronkite, David | Hess, Chantelle | Bowers, Will | Schaaf, Beverly | Gray, Regan | Guerrero, Linda | Sankaran, Sundary | Gatto, Nicole
Article Type: Research Article
Abstract: Background: Conflicting research on retinal biomarkers of Alzheimer’s disease and related dementias (AD/ADRD) is likely related to limited sample sizes, study design, and protocol differences. Objective: The prospective Eye Adult Changes in Thought (Eye ACT) seeks to address these gaps. Methods: Eye ACT participants are recruited from ACT, an ongoing cohort of dementia-free, older adults followed biennially until AD/ADRD, and undergo visual function and retinal imaging assessment either in clinic or at home. Results: 330 participants were recruited as of 03/2023. Compared to ACT participants not in Eye ACT (N = 1868), Eye ACT participants (N … = 330) are younger (mean age: 70.3 versus 71.2, p = 0.014), newer to ACT (median ACT visits since baseline: 3 versus 4, p < 0.001), have more years of education (17.7 versus 16.2, p < 0.001) and had lower rates of visual impairment (12% versus 22%, p < 0.001). Compared to those seen in clinic (N = 300), Eye ACT participants seen at home (N = 30) are older (77.2 versus 74.9, p = 0.015), more frequently female (60% versus 49%, p = 0.026), and have significantly worse visual acuity (71.1 versus 78.9 Early Treatment Diabetic Retinopathy Study letters, p < 0.001) and contrast sensitivity (–1.9 versus –2.1 mean log units at 3 cycles per degree, p = 0.002). Cognitive scores and retinal imaging measurements are similar between the two groups. Conclusions: Participants assessed at home had significantly worse visual function than those seen in clinic. By including these participants, Eye ACT provides a unique longitudinal cohort for evaluating potential retinal biomarkers of dementia. Show more
Keywords: Adult Changes in Thought (ACT), age-related macular degeneration, Alzheimer’s disease, Cognitive Abilities Screening Instrument (CASI) score, contrast sensitivity, Eye Adult Changes in Thought (Eye ACT), ophthalmology, optical coherence measurement, prospective study, visual acuity
DOI: 10.3233/JAD-240203
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2024
Authors: Chino, Brenda | López-Sanz, David | Doval, Sandra | Torres-Simón, Lucía | de Frutos Lucas, Jaisalmer | Giménez-Llort, Lydia | Zegarra-Valdivia, Jonathan | Maestú, Fernando
Article Type: Systematic Review
Abstract: Background: Aging is a complex and natural process. The physiological decline related to aging is accompanied by a slowdown in cognitive processes, which begins shortly after individuals reach maturity. These changes have been sometimes interpreted as a compensatory sign and others as a fingerprint of deterioration. Objective: In this context, our aim is to uncover the mechanisms that underlie and support normal cognitive functioning in the brain during the later stages of life. Methods: With this purpose, a systematic literature search was conducted using PubMed, Scopus, and Web of Science databases, which identified 781 potential articles. …After applying inclusion and exclusion criteria, we selected 12 studies that examined the brain oscillations patterns in resting-state conditions associated with cognitive performance in cognitively unimpaired older adults. Results: Although cognitive healthy aging was characterized differently across studies, and various approaches to analyzing brain activity were employed, our review indicates a relationship between alpha peak frequency (APF) and improved performance in neuropsychological scores among cognitively unimpaired older adults. Conclusions: A higher APF is linked with a higher score in intelligence, executive function, and general cognitive performance, and could be considered an optimal, and easy-to-assess, electrophysiological marker of cognitive health in older adults. Show more
Keywords: Aging, alpha peak frequency, Alzheimer’s disease, cognitive performance, cognitively unimpaired, resting-state, systematic review
DOI: 10.3233/JAD-231009
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-16, 2024
Authors: Michalowsky, Bernhard | Rädke, Anika | Scharf, Annelie | Mühlichen, Franka | Buchholz, Maresa | Platen, Moritz | Kleinke, Fabian | Penndorf, Peter | Pfitzner, Stefanie | van den Berg, Neeltje | Hoffmann, Wolfgang
Article Type: Research Article
Abstract: Background: Determining unmet need patterns and associated factors in primary care can potentially specify assessment batteries and tailor interventions in dementia more efficiently. Objective: To identify latent unmet healthcare need patterns and associated sociodemographic and clinical factors. Methods: This Latent Class Analysis (LCA) includes n = 417 community-dwelling people living with dementia. Subjects completed a comprehensive, computer-assisted face-to-face interview to identify unmet needs. One-hundred-fifteen predefined unmet medical, medication, nursing, psychosocial, and social care needs were available. LCA and multivariate logistic regressions were performed to identify unmet needs patterns and patient characteristics belonging to a specific pattern, respectively. …Results: Four profiles were identified: [1 ] “few needs without any psychosocial need” (n = 44 (11%); mean: 7.4 needs), [2 ] “some medical and nursing care needs only” (n = 135 (32%); 9.7 needs), [3 ] “some needs in all areas” (n = 139 (33%); 14.3 needs), and [4 ] “many medical and nursing needs” (n = 99 (24%); 19.1 needs). Whereas the first class with the lowest number of needs comprised younger, less cognitively impaired patients without depressive symptoms, the fourth class had the highest number of unmet needs, containing patients with lower health status, less social support and higher comorbidity and depressive symptoms. Better access to social care services and higher social support reduced unmet needs, distinguishing the second from the third class (9.7 versus 14.3 needs). Conclusions: Access to the social care system, social support and depressive symptoms should be assessed, and the patient’s health status and comorbidities monitored to more comprehensively identify unmet needs patterns and more efficiently guide tailored interventions. Show more
Keywords: Alzheimer’s disease, dementia, latent class analysis, primary care, profiles, unmet needs
DOI: 10.3233/JAD-240025
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2024
Authors: Loeffler, David A.
Article Type: Review Article
Abstract: Amyloid protein-β (Aβ) concentrations are increased in the brain in both early onset and late onset Alzheimer’s disease (AD). In early onset AD, cerebral Aβ production is increased and its clearance is decreased, while increased Aβ burden in late onset AD is due to impaired clearance. Aβ has been the focus of AD therapeutics since development of the amyloid hypothesis, but efforts to slow AD progression by lowering brain Aβ failed until phase 3 trials with the monoclonal antibodies lecanemab and donanemab. In addition to promoting phagocytic clearance of Aβ, antibodies lower cerebral Aβ by efflux of Aβ-antibody complexes across …the capillary endothelia, dissolving Aβ aggregates, and a “peripheral sink” mechanism. Although the blood-brain barrier is the main route by which soluble Aβ leaves the brain (facilitated by low-density lipoprotein receptor-related protein-1 and ATP-binding cassette sub-family B member 1), Aβ can also be removed via the blood-cerebrospinal fluid barrier, glymphatic drainage, and intramural periarterial drainage. This review discusses experimental approaches to increase cerebral Aβ efflux via these mechanisms, clinical applications of these approaches, and findings in clinical trials with these approaches in patients with AD or mild cognitive impairment. Based on negative findings in clinical trials with previous approaches targeting monomeric Aβ, increasing the cerebral efflux of soluble Aβ is unlikely to slow AD progression if used as monotherapy. But if used as an adjunct to treatment with lecanemab or donanemab, this approach might allow greater slowing of AD progression than treatment with either antibody alone. Show more
Keywords: Alzheimer’s disease, amyloid-β , blood-brain barrier, blood-cerebrospinal fluid barrier, experimental approaches, glymphatic drainage, perivascular drainage)
DOI: 10.3233/JAD-240212
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-33, 2024
Authors: Li, Dazhi | Xie, Qiang | Xie, Jikui | Ni, Ming | Wang, Jinliang | Gao, Yuru | Wang, Yaxin | Tang, Qiqiang
Article Type: Research Article
Abstract: Background: Early-onset Alzheimer’s disease (EOAD) exhibits a notable degree of heterogeneity as compared to late-onset Alzheimer’s disease (LOAD). The proteins and pathways contributing to the pathophysiology of EOAD still need to be completed and elucidated. Objective: Using correlation network analysis and machine learning to analyze cerebrospinal fluid (CSF) proteomics data to identify potential biomarkers and pathways associated with EOAD. Methods: We employed mass spectrometry to conduct CSF proteomic analysis using the data-independent acquisition method in a Chinese cohort of 139 CSF samples, including 40 individuals with normal cognition (CN), 61 patients with EOAD, and 38 patients …with LOAD. Correlation network analysis of differentially expressed proteins was performed to identify EOAD-associated pathways. Machine learning assisted in identifying crucial proteins differentiating EOAD. We validated the results in an Western cohort and examined the proteins expression by enzyme-linked immunosorbent assay (ELISA) in additional 9 EOAD, 9 LOAD, and 9 CN samples from our cohort. Results: We quantified 2,168 CSF proteins. Following adjustment for age and sex, EOAD exhibited a significantly greater number of differentially expressed proteins than LOAD compared to CN. Additionally, our data indicates that EOAD may exhibit more pronounced synaptic dysfunction than LOAD. Three potential biomarkers for EOAD were identified: SH3BGRL3, LRP8, and LY6 H, of which SH3BGRL3 also accurately classified EOAD in the Western cohort. LY6 H reduction was confirmed via ELISA, which was consistent with our proteomic results Conclusions: This study provides a comprehensive profile of the CSF proteome in EOAD and identifies three potential EOAD biomarker proteins. Show more
Keywords: Alzheimer’s disease, early-onset Alzheimer’s disease, biomarker, cerebrospinal fluid, machine learning, proteomics
DOI: 10.3233/JAD-240022
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-17, 2024
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