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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: Taylor, Morag E. | Kerckhaert, Luuk | Close, Jacqueline C.T. | van Schooten, Kimberley S. | Lord, Stephen R.
Article Type: Research Article
Abstract: Background: Cognitive impairment (CI) may impair the ability to accurately perceive physical capacity and fall risk. Objective: We investigated perceived (measured as concern about falls) and physiological fall risk in community-dwelling older people with CI, the characteristics of the aligned and misaligned groups and the impact of misaligned perceptions on falls. Methods: Participants (n = 293) with mild-moderate CI were classified into four groups based on validated physiological and perceived fall risk assessments: 1) vigorous: low perceived and physiological fall risk; 2) anxious: high perceived and low physiological fall risk; 3) unaware: low perceived and high physiological …fall risk; and 4) aware: high perceived and physiological fall risk. Groups were compared with respect to neuropsychological and physical function, activity and quality of life measures, and prospective falls (12-months). Results: The anxious (IRR = 1.70, 95% CI = 1.02–2.84), unaware (IRR = 2.00, 95% CI = 1.22–3.26), and aware (IRR = 2.53, 95% CI = 1.67–3.84) groups had significantly higher fall rates than the vigorous group but fall rates did not significantly differ among these groups. Compared with the vigorous group: the anxious group had higher depression scores and reduced mobility and quality of life; the unaware group had poorer global cognition, executive function and mobility and lower physical activity levels; and the aware group had an increased prevalence of multiple physical and cognitive fall risk factors. Conclusions: Fall rates were increased in participants who had increased perceived and/or physiological fall risk. Contrasting fall risk patterns were evident in those who under- and over-estimated their fall risk. Understanding these characteristics will help guide fall risk assessment and prevention strategies in community-dwelling older people with CI. Show more
Keywords: Accidental falls, aged, Alzheimer’s disease, cognitive dysfunction, dementia, fear of falling, perception, risk factors
DOI: 10.3233/JAD-240489
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2024
Authors: Therrien, Sarah | Anthony, Mia | Turnbull, Adam | Lin, F. Vankee
Article Type: Research Article
Abstract: Background: Adequately evaluating risk and making decisions is vital but understudied for older adults living independently but with compromised cognition, as seen in those with mild cognitive impairment (MCI), specifically those with amnestic MCI (aMCI) which is associated with higher risk of conversion to Alzheimer’s disease. Objective: We propose to comprehensively evaluate risk-taking behaviors across domains important for everyday activities between an aMCI group and their cognitively healthy counterparts (HC). Methods: A case-control study design. Data on risk-taking behaviors via the Domain-Specific Risk-Taking Scale (DOSPERT), and candidate confounding mental health factors (i.e., neurodegeneration, depression, and fatigue) …were collected. Analyses on group difference and interaction between group and confounding factors on risk-taking behaviors were conducted. Results: The aMCI group showed a higher likelihood of risk-taking than HC (t = 4.38, df = 73, p < 0.001). Moderation analysis showed fatigue (F = 5.91, p = 0.018) and presence of depression (F = 4.52, p = 0.037), but not neurodegeneration, as significant moderators for group and DOSPERT total score, controlling for sex. In post-hoc analyses, there was a significant relationship between both fatigue (B = –7.83, SE = 3.65, t = –2.14, p = 0.036), and presence of depression (B = –20.80, SE = 9.97, t = –2.09, p = 0.041), with DOSPERT total score for HC but not for aMCI. There were no significant relationships between neurodegeneration, fatigue, or depression with any specific risk-taking domains after correction for multiple comparisons. Conclusions: Our results show differences in risk-taking behavior between older adults with and without intact cognition, and overall decision-making is affected by fatigue and depression in HC but not aMCI, together suggesting the importance of cognition in the ability to adjust risk-taking behaviors. Show more
Keywords: Alzheimer’s disease, decision making, functional status, mild cognitive impairment, risk-taking
DOI: 10.3233/JAD-231448
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2024
Authors: Elman, Jeremy A. | Schork, Nicholas J. | Rangan, Aaditya V.
Article Type: Research Article
Abstract: Background: Alzheimer’s disease (AD) exhibits considerable phenotypic heterogeneity, suggesting the potential existence of subtypes. AD is under substantial genetic influence, thus identifying systematic variation in genetic risk may provide insights into disease origins. Objective: We investigated genetic heterogeneity in AD risk through a multi-step analysis. Methods: We performed principal component analysis (PCA) on AD-associated variants in the UK Biobank (AD cases = 2,739, controls = 5,478) to assess structured genetic heterogeneity. Subsequently, a biclustering algorithm searched for distinct disease-specific genetic signatures among subsets of cases. Replication tests were conducted using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset (AD cases = 500, controls = 470). …We categorized a separate set of ADNI individuals with mild cognitive impairment (MCI; n = 399) into genetic subtypes and examined cognitive, amyloid, and tau trajectories. Results: PCA revealed three distinct clusters (“constellations”) driven primarily by different correlation patterns in a region of strong LD surrounding the MAPT locus. Constellations contained a mixture of cases and controls, reflecting disease-relevant but not disease-specific structure. We found two disease-specific biclusters among AD cases. Pathway analysis linked bicluster-associated variants to neuron morphogenesis and outgrowth. Disease-relevant and disease-specific structure replicated in ADNI, and bicluster 2 exhibited increased cerebrospinal fluid p-tau and cognitive decline over time. Conclusions: This study unveils a hierarchical structure of AD genetic risk. Disease-relevant constellations may represent haplotype structure that does not increase risk directly but may alter the relative importance of other genetic risk factors. Biclusters may represent distinct AD genetic subtypes. This structure is replicable and relates to differential pathological accumulation and cognitive decline over time. Show more
Keywords: Alzheimer’s disease, biclustering, genetic risk, genetic subtypes, genotyping
DOI: 10.3233/JAD-231252
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-18, 2024
Authors: Mace, Ryan A. | Lyons, Christopher | Cohen, Joshua E. | Ritchie, Christine | Bartels, Stephen | Okereke, Olivia I. | Hoeppner, Bettina B. | Brewer, Judson A. | Vranceanu, Ana-Maria
Article Type: Research Article
Abstract: Background: Interventions that promote healthy lifestyles are critical for the prevention of Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD). However, knowledge of the best practices for implementing AD/ADRD prevention in healthcare settings remains limited. Objective: We aimed to qualitatively identify barriers and facilitators to implementing a clinical trial of a novel lifestyle intervention (My Healthy Brain ) in our medical center for older patients with subjective cognitive decline who are at-risk for AD/ADRD. Methods: We conducted focus groups with 26 healthcare professionals (e.g., physicians, psychology, nursing) from 5 clinics that treat older patients (e.g., memory …care, psychiatry). Our qualitative analysis integrated two implementation frameworks to systematically capture barriers and facilitators to AD/ADRD prevention (Consolidated Framework for Implementation Science Research) that impact implementation outcomes of acceptability, appropriateness, and feasibility (Proctor’s framework). Results: We found widespread support for an RCT of My Healthy Brain and AD/ADRD prevention. Participants identified barriers related to patients (stigma, technological skills), providers (dismissiveness of “worried well,” doubting capacity for behavior change), clinics (limited time and resources), and the larger healthcare system (underemphasis on prevention). Implementation strategies guided by Expert Recommendations for Implementing Change (ERIC) included: developing tailored materials, training staff, obtaining buy-in from leadership, addressing stigmatized language and practices, identifying “champions,” and integrating with workflows and resources. Conclusions: The results will inform our recruitment, enrollment, and retention procedures to implement the first randomized clinical trial of My Healthy Brain . Our study provides a blueprint for addressing multi-level barriers to the implementation of AD/ADRD prevention for older patients in medical settings. Show more
Keywords: Alzheimer’s disease, brain health, dementia, implementation, prevention, qualitative
DOI: 10.3233/JAD-240365
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-23, 2024
Authors: Amaral-Carvalho, Viviane | Bento Lima-Silva, Thais | Inácio Mariano, Luciano | Cruz de Souza, Leonardo | Cerqueira Guimarães, Henrique | Santoro Bahia, Valéria | Nitrini, Ricardo | Tonidandel Barbosa, Maira | Sanches Yassuda, Mônica | Caramelli, Paulo
Article Type: Research Article
Abstract: Background: The Addenbrooke’s Cognitive Examination-Revised (ACE-R) is an accessible cognitive tool that supports the early detection of mild cognitive impairment (MCI), Alzheimer’s disease (AD), and behavioral variant frontotemporal dementia (bvFTD). Objective: To investigate the diagnostic efficacy of the ACE-R in MCI, AD, and bvFTD through the identification of novel coefficients for differentiation between these diseases. Methods: We assessed 387 individuals: 102 mild AD, 37 mild bvFTD, 87 with amnestic MCI patients, and 161 cognitively unimpaired controls. The Mokken scaling technique facilitated the extraction out of the 26 ACE-R items that exhibited a common latent trait, thereby …generating the Mokken scales for the AD group and the MCI group. Subsequently, we performed logistic regression, integrating each Mokken scales with sociodemographic factors, to differentiate between AD and bvFTD, as well as between AD or MCI and control groups. Ultimately, the Receiver Operating Characteristic curve analysis was employed to assess the efficacy of the coefficient’s discrimination. Results: The AD-specific Mokken scale (AD-MokACE-R) versus bvFTD exhibited an Area Under the Curve (AUC) of 0.922 (88% sensitivity and specificity). The AD-MokACE-R versus controls achieved an AUC of 0.968 (93% sensitivity, 94% specificity). The MCI-specific scale (MCI-MokACE-R) versus controls demonstrated an AUC of 0.859 (78% sensitivity, 79% specificity). Conclusions: The ACE-R’s capacity is enhanced through statistical methods and demographic integration, allowing for accurate differentiation between AD and bvFTD, as well as between MCI and controls. This new method not only reinforces its clinical value in early diagnosis but also surpasses traditional approaches noted in prior studies. Show more
Keywords: Aging, Alzheimer’s disease, cognition, dementia, frontotemporal dementia, mild cognitive impairment, neuropsychological tests
DOI: 10.3233/JAD-240554
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2024
Authors: Sommerlad, Andrew | Grothe, Jessica | Umeda, Sumiyo | Ikeda, Manabu | Kanemoto, Hideki | Livingston, Gill | Luppa, Melanie | Rankin, Katherine P. | Riedel-Heller, Steffi G. | Röhr, Susanne | Suzuki, Maki | Huntley, Jonathan
Article Type: Research Article
Abstract: Background: People with dementia commonly have impaired social functioning and may not recognize this. This lack of awareness may result in worse outcomes for the person and their family carers. Objective: We aimed to characterize awareness of social functioning in dementia and describe its association with dementia severity. Methods: Multi-center cross-sectional study of people aged >65 years with dementia and family informants recruited from Germany, Japan and the United Kingdom. We used the Social Functioning in Dementia (SF-DEM) scale, assessing “spending time with other people” (domain 1), “communicating with other people” (domain 2), and “sensitivity to …other people” (domain 3), and calculated lack of awareness into social functioning as the discrepancy between patient and informant ratings. Results: 108 participants with dementia (50.9% women), mean age = 78.9 years, and mean MMSE score = 22.7. Patient and informant domain 1 ratings did not differ, but patient-rating was higher than carers for domain 2 (11.2 versus 10.1; p = 0.003) and domain 3 (9.7 versus 8.1; p < 0.001). Sixty people with dementia overestimated their overall social functioning, 30 underestimated, and 18 gave ratings congruent with their informant. Performance on the MMSE and its sub-domains was not associated with SF-DEM discrepancy score. Conclusions: We found that awareness of social functioning in dementia was a multidimensional concept, which varies according to subdomains of social functioning. Clinicians should help family members understand and adapt by explaining their relative with dementia’s lack of awareness about aspects of their social functioning. Show more
Keywords: Alzheimer’s disease, awareness, dementia, insight, metacognition, social functioning
DOI: 10.3233/JAD-240311
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2024
Authors: Rice, Paige E. | Thumuluri, Deepthi | Barnstaple, Rebecca | Fanning, Jason | Laurita-Spanglet, Jessie | Soriano, Christina T. | Hugenschmidt, Christina E.
Article Type: Review Article
Abstract: Background: Dance combines cultural and aesthetic elements with behaviors important for brain health, including physical activity, social engagement, and cognitive challenge. Therefore, dance could positively impact public health given the rapidly aging population, increasing incidence of Alzheimer’s disease and related dementias, and lack of uptake of exercise in many older adults. Despite a high volume of literature, existing literature does not support evidence-based guidelines for dance to support healthy aging. Objective: To conduct a scoping review of the dance intervention literature in older adults and provide information to facilitate a more consistent approach among scientists in designing dance …interventions for older adults that stimulate physical and neurocognitive health adaptations. Methods: Study characteristics (sample size, population, study design, outcomes, intervention details) were ascertained from 112 separate studies of dance reported in 127 papers that reported outcomes important for brain health (cardiorespiratory fitness, balance and mobility, cognition, mood, and quality of life). Results: High heterogeneity across studies was evident. Class frequency ranged from < 1 to 5 classes per week, class length from 30–120 minutes, and intervention duration from 2 weeks to 18 months. Studies often did not randomize participants, had small (< 30) sample sizes, and used varied comparator conditions. Over 50 tests of cognition, 40 dance forms, and 30 tests of mobility were identified. Conclusions: Based on these results, important future directions are establishing common data elements, developing intervention mapping and mechanistic modeling, and testing dosing parameters to strengthen and focus trial design of future studies and generate evidence-based guidelines for dance. Show more
Keywords: Aging, Alzheimer’s disease, cardiorespiratory fitness, cognition, health, physical fitness, physical function performance
DOI: 10.3233/JAD-230741
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-38, 2024
Authors: Fan, Meixiang | Li, Qingfeng | Yang, Tingting | Yang, Yinghua | Chen, Zhihua | Xuan, Guo | Ruan, Ye | Sun, Shuangyuan | Wang, Meng | Chen, Xiaoli | Huang, Yanyan | Yang, Zhi | Wang, Ying
Article Type: Research Article
Abstract: Background: Previous trials have indicated that multimodal training could improve cognitive functions and moods in individuals with mild cognitive impairment (MCI). However, evidence was mainly obtained from studies in high-income countries. Objective: This trial aims to investigate the efficacy, safety, and potential mechanism of a multimodal intervention on cognitive function in individuals with MCI living in a community. Methods: In this single-blind, randomized controlled trial, 120 participants with MCI were randomly assigned to either the intervention group or the control group. The intervention group received the multimodal intervention, while the control group received regular health education. …Neuropsychological tests and magnetic resonance imaging (MRI) were conducted at baseline and after the 12-week intervention. Results: Fifty-nine and fifty-seven participants respectively in the intervention and control groups completed the trial. The intervention group shown improvements in primary outcome, Mini-Mental State Exam (MMSE) total score (mean difference –0.96, 95% CI [–1.58, –0.34], p = 0.003), and secondary outcomes: MMSE recall (–0.39, 95% CI [–0.71, –0.07], p = 0.019), MMSE language (–0.26, 95% CI [–0.44, –0.07], p = 0.007), Auditory Verbal Learning Test instantaneous memory (–3.30, 95% CI [–5.70, –0.89], p = 0.008), Digit Symbol Substitution Test total score (–2.91, 95% CI [–5.67, –0.15], p = 0.039), digit span forwards (–1.25, 95% CI [–1.93, –0.56], p < 0.001), and Digit Span Test (–1.33, 95% CI [–2.33, –0.34], p = 0.009) compared to the control group. Improvements were observed in structural and functional connectivity related to language, concentration, executive function, memory, and recall functioning via MRI in the intervention group. Conclusions: The multimodal intervention improved cognitive function in individuals with MCI in cognitive performance and neuroimaging. Show more
Keywords: Alzheimer’s disease, behavior therapy, clinical trial, cognitive dysfunction
DOI: 10.3233/JAD-231370
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2024
Authors: Brar, Manjot | Mc Ardle, Ríona | Hagan, Alexander | Al-Oraibi, Amani | Hanjari, Matilda | Stephan, Blossom | Brayne, Carol | Lafortune, Louise | Bains, Manpreet | Qureshi, Nadeem | Robinson, Louise
Article Type: Systematic Review
Abstract: Background: Increased understanding of dementia risk-reduction and early detection of Alzheimer’s disease and related disorders has spurred interest in the identification of risks for dementia, underlying putative biologies, or dementia itself. Implementation of such approaches require acceptability to the public. Research prior to 2012 indicated limited acceptability for population dementia screening. The changing landscape of dementia prevention research may influence recent perceptions. Additionally, perspectives from underserved populations, such as ethnic minorities and low socio-economic groups, are lacking. Objective: In this systematic review, we sought published studies since 2012 on attitudes and preferences of people with dementia, carers and …the general public from ethnic minorities and low socio-economic groups regarding dementia screening. Methods: This review was preregistered on PROSPERO (CRD42023384115) and followed PRISMA guidelines. Key search terms were entered into five databases. Articles were included if they focused on population or risk screening for dementia via primary/community care-based assessments, and which included majority ethnic minority or low socio-economic groups or discretely considered these groups in data analysis. Data were synthesized narratively. Results: Seven studies reported perspectives of ethnic minorities regarding dementia screening; one study included people from low socio-economic groups. Results indicated that participants from ethnic minorities were willing to undergo dementia screening. Predictors of willingness included belief in benefits, desire to boost diversity, and to implement lifestyle changes. Unwillingness was associated with anxiety regarding results. Conclusions: Although there seems to be high acceptability for screening in the studied groups, more research is necessary to explore the practical considerations for screening such as cultural and economic barriers, trust, and post-screening actions. Show more
Keywords: Alzheimer’s disease, attitudes, dementia, ethnic minorities, low socioeconomic status, preferences, screening
DOI: 10.3233/JAD-240315
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-17, 2024
Authors: Gonzales, Mitzi M. | Kojis, Daniel | Spartano, Nicole L. | Thibault, Emma G. | DeCarli, Charles S. | El Fakhri, Georges | Johnson, Keith A. | Beiser, Alexa S. | Seshadri, Sudha
Article Type: Research Article
Abstract: Background: Higher midlife physical activity engagement has been associated with lower dementia risk in late life. However, the underlying mechanisms contributing to the protective effect remain unclear. Objective: The goal of the current study was to evaluate the associations of physical activity with cerebral amyloid-β (Aβ) and tau in a predominately middle-aged community-based cohort, as well as to explore whether the associations differ by sex or age. Methods: Participants from the Framingham Heart Study underwent 11 C-Pittsburgh Compound B amyloid and 18 F-Flortaucipir tau positron emission tomography (PET) imaging. Total physical activity levels were evaluated by …self-report using the Physical Activity Index (PAI). Cross-sectional associations between total PAI with regional Aβ and tau PET retention were evaluated using linear regression models adjusted for demographic and cardiovascular risk factors. Interactions with sex and age group were examined and stratified analyses were performed when significant. FDR-correction for multiple comparisons was applied. Results: The sample included 354 participants (mean age 53±8 years, 51% female). Higher total PAI scores were associated with lower entorhinal cortex tau PET binding (β (SE) = –0.021(0.008), p = 0.049). There were significant interactions with sex. In men alone, total PAI inversely associated with entorhinal cortex (β (SE) = –0.035(0.009), p = 0.001), inferior temporal (β (SE) = –0.029(0.010), p = 0.012), and rhinal cortex tau(β (SE) = –0.033(0.010), p = 0.002). Conclusions: The results suggest that higher midlife physical activity engagement may confer resistance to tau pathology. However, the effects may vary based on sex, highlighting the importance of better understanding and tailoring lifestyle interventions to address sex disparities. Show more
Keywords: Alzheimer’s disease, amyloid-β, midlife, PET imaging, physical activity, tau
DOI: 10.3233/JAD-240322
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2024
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