Journal of Alzheimer's Disease - Volume 79, issue 1

Authors: Krell-Roesch, Janina | Syrjanen, Jeremy A. | Bezold, Jelena | Trautwein, Sandra | Barisch-Fritz, Bettina | Boes, Klaus | Woll, Alexander | Forzani, Erica | Kremers, Walter K. | Machulda, Mary M. | Mielke, Michelle M. | Knopman, David S. | Petersen, Ronald C. | Vassilaki, Maria | Geda, Yonas E.

Article Type: Research Article

Abstract: Background: Little is known about the association between physical activity (PA) and cognitive trajectories in older adults. Objective: To examine the association between PA and change in memory, language, attention, visuospatial skills, and global cognition, and a potential impact of sex or Apolipoprotein E (APOE ) ɛ4 status. Methods: Longitudinal study derived from the population-based Mayo Clinic Study of Aging, including 2,060 cognitively unimpaired males and females aged ≥70 years. Engagement in midlife (ages 50–65) and late-life (last year) PA was assessed using a questionnaire. Neuropsychological testing was done every 15 months (mean follow-up 5.8 years). …We ran linear mixed-effect models to examine whether mid- or late-life PA at three intensities (mild, moderate, vigorous) was associated with cognitive z-scores. Results: Light intensity midlife PA was associated with less decline in memory function compared to the no-PA reference group (time x light PA; estimate [standard error] 0.047 [0.016], p  = 0.004). Vigorous late-life PA was associated with less decline in language (0.033 [0.015], p  = 0.030), attention (0.032 [0.017], p  = 0.050), and global cognition (0.039 [0.016], p  = 0.012). Females who were physically inactive in midlife experienced more pronounced cognitive decline than females physically active in midlife and males regardless of PA (p -values for time interaction terms with midlife PA levels and sex were all p  < 0.05 for global cognition). APOE ɛ4 carriership did not moderate the association between PA and cognition. Conclusion: Engaging in PA, particularly of vigorous intensity in late-life, was associated with less pronounced decline in global and domain-specific cognition. This association may differ by sex. Show more

Keywords: Cognitive trajectories, community-dwelling persons, late-life, midlife, physical activity

DOI: 10.3233/JAD-200959

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 377-388, 2021

Authors: Beach, Thomas G. | Malek-Ahmadi, Michael

Article Type: Research Article

Abstract: Background: Clinicopathological studies have demonstrated that Alzheimer’s disease dementia (ADD) is often accompanied by clinically undetectable comorbid neurodegenerative and cerebrovascular disease that alter the rate of cognitive decline. Aside from causing increased variability in clinical response, it is possible that the major ADD comorbidities may not respond to ADD-specific molecular therapeutics. Objective: As most reports have focused on comorbidity in the oldest-old, its extent in younger age groups that are more likely to be involved in clinical trials is largely unknown; our objective is to provide this information. Methods: We conducted a survey of neuropathological comorbidities …in sporadic ADD using data from the US National Alzheimer’s Coordinating Center. Subject data was restricted to those with dementia and meeting National Institute on Aging-Alzheimer’s Association intermediate or high AD Neuropathological Change levels, excluding those with known autosomal dominant AD-related mutations. Results: Highly prevalent ADD comorbidities are not restricted to the oldest-old but are common even in early-onset ADD. The percentage of cases with ADD as the sole major neuropathological diagnosis is highest in the under-60 group, where “pure” ADD cases are still in the minority at 44%. After this AD as a sole major pathology in ADD declines to roughly 20%in the 70s and beyond. Lewy body disease is the most common comorbidity at younger ages but actually is less common at later ages, while for most others, their prevalence increases with age. Conclusion: Alzheimer’s disease neuropathological comorbidities are highly prevalent even in the younger-old. Show more

Keywords: Cerebrovascular, infarct, Lewy bodies, TDP-43, tau, white matter

DOI: 10.3233/JAD-201213

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 389-400, 2021

Authors: Toepper, Max | Schulz, Philipp | Beblo, Thomas | Driessen, Martin

Article Type: Research Article

Abstract: Background: On-road driving behavior can be impaired in older drivers and particularly in drivers with mild cognitive impairment (MCI). Objective: To determine whether cognitive and non-cognitive risk factors for driving safety may allow an accurate and economic prediction of on-road driving skills, fitness to drive, and prospective accident risk in healthy older drivers and drivers with MCI, we examined a representative combined sample of older drivers with and without MCI (N = 74) in an observational on-road study. In particular, we examined whether non-cognitive risk factors improve predictive accuracy provided by cognitive factors alone. Methods: Multiple and logistic …hierarchical regression analyses were utilized to predict different driving outcomes. In all regression models, we included cognitive predictors alone in a first step and added non-cognitive predictors in a second step. Results: Results revealed that the combination of cognitive and non-cognitive risk factors significantly predicted driving skills (R2 adjusted = 0.30) and fitness to drive (81.2% accuracy) as well as the number (R2 adjusted = 0.21) and occurrence (88.3% accuracy) of prospective minor at-fault accidents within the next 12 months. In all analyses, the inclusion of non-cognitive risk factors led to a significant increase of explained variance in the different outcome variables. Conclusion: Our findings suggest that a combination of the most robust cognitive and non-cognitive risk factors may allow an economic and accurate prediction of on-road driving performance and prospective accident risk in healthy older drivers and drivers with MCI. Therefore, non-cognitive risk factors appear to play an important role. Show more

Keywords: Accident risk, driving skills, fitness to drive, mild cognitive impairment, older drivers, risk factors

DOI: 10.3233/JAD-200943

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 401-414, 2021

Authors: Montagut, Núria | Borrego-Écija, Sergi | Castellví, Magdalena | Rico, Immaculada | Reñé, Ramón | Balasa, Mircea | Lladó, Albert | Sánchez-Valle, Raquel

Article Type: Research Article

Abstract: Background: The semantic variant of primary progressive aphasia (svPPA) is characterized by a progressive loss of semantic knowledge impairing the ability to name and to recognize the meaning of words. Objective: We aimed to evaluate the immediate and short-term effect of errorless learning speech therapy on the naming and recognition of commonly used words in patients with svPPA. Methods: Eight participants diagnosed with svPPA received 16 sessions of intensive errorless learning speech therapy. Naming and word comprehension tasks were evaluated at baseline, immediately postintervention, and at follow-up after 1, 3, and 6 months. These evaluations were …performed using two item sets (a trained list and an untrained list). Results: In the naming tasks, patients showed a significant improvement in trained items immediately after the intervention, but that improvement decayed progressively when therapy ended. No improvements were found either in trained comprehension or in untrained tasks. Conclusion: Errorless learning therapy could improve naming ability in patients with svPPA. This effect may be due to the relative preservation of episodic memory, but the benefit is not maintained over time, presumably because there is no consolidation. Show more

Keywords: Alzheimer's disease, anomia, errorless learning, relearning, semantic dementia, semantic variant of primary progressive aphasia, speech therapy

DOI: 10.3233/JAD-200904

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 415-422, 2021

Authors: Birkenbihl, Colin | Westwood, Sarah | Shi, Liu | Nevado-Holgado, Alejo | Westman, Eric | Lovestone, Simon | on behalf of the AddNeuroMed Consortium | Hofmann-Apitius, Martin

Article Type: Research Article

Abstract: Background: Accessible datasets are of fundamental importance to the advancement of Alzheimer’s disease (AD) research. The AddNeuroMed consortium conducted a longitudinal observational cohort study with the aim to discover AD biomarkers. During this study, a broad selection of data modalities was measured including clinical assessments, magnetic resonance imaging, genotyping, transcriptomic profiling, and blood plasma proteomics. Some of the collected data were shared with third-party researchers. However, this data was incomplete, erroneous, and lacking in interoperability. Objective: To provide the research community with an accessible, multimodal, patient-level AD cohort dataset. Methods: We systematically addressed several limitations of …the originally shared resources and provided additional unreleased data to enhance the dataset. Results: In this work, we publish and describe ANMerge, a new version of the AddNeuroMed dataset. ANMerge includes multimodal data from 1,702 study participants and is accessible to the research community via a centralized portal. Conclusion: ANMerge is an information rich patient-level data resource that can serve as a discovery and validation cohort for data-driven AD research, such as, for example, machine learning and artificial intelligence approaches. Show more

Keywords: AddNeuroMed, Alzheimer’s disease, biomarkers, cohort analysis, cohort studies, data-driven science, dataset, dementia, genome wide association studies, magnetic resonance imaging, multimodal

DOI: 10.3233/JAD-200948

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 423-431, 2021

Authors: Estrella, Mayra L. | Durazo-Arvizu, Ramon A. | Gallo, Linda C. | Tarraf, Wassim | Isasi, Carmen R. | Perreira, Krista M. | Zeng, Donglin | Marquine, Maria J. | Lipton, Richard B. | González, Hector M. | Daviglus, Martha L. | Lamar, Melissa

Article Type: Research Article

Abstract: Background: Evidence suggests that psychosocial factors are associated with cognitive health in older adults; however, associations of psychosocial factors with cognition remain largely unexamined in middle-aged and older Hispanics/Latinos. Objective: To examine the cross-sectional associations of psychosocial factors with cognitive function among middle-aged and older Hispanics/Latinos living in the US. Methods: Baseline (2008–2011) data from the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study (n  = 2,818; ages 45–74) were used to examine the associations of each psychosocial factor with global cognition (GC), verbal learning, verbal memory, verbal fluency, and processing speed independent of age, sex, …education, Hispanic/Latino background, income, language, and depressive symptoms. Psychosocial variables included: intrapersonal factors (ethnic identity, optimism, and purpose in life), interpersonal factors (family cohesion, familism, social network embeddedness, and social support), and social stressors (perceived ethnic discrimination, loneliness, and subjective social status). Results: In fully-adjusted models, purpose in life and social support were each positively associated with all five cognitive variables. Loneliness was negatively associated with GC, verbal learning, memory, and processing speed. Ethnic identity was positively and familism negatively associated with GC, verbal fluency, and processing speed. Family cohesion was positively associated with verbal learning. Conclusion: These findings extend previous evidence from older, largely non-Hispanic White cohorts to show that higher purpose in life and social support are also strongly associated with cognitive health among middle-aged and older Hispanics/Latinos. We also highlight that intrapersonal factors, interpersonal factors, and social stressors have differential relationships with individual cognitive tests. Show more

Keywords: Cognitive aging, cognitive function, Hispanics, Latinos, psychosocial factors

DOI: 10.3233/JAD-200612

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 433-449, 2021

Authors: Ramos, Jairo | Chowdhury, Aneesa R. | Caywood, Laura J. | Prough, Michael | Denise Fuzzell, M. | Fuzzell, Sarada | Miskimen, Kristy | Whitehead, Patrice L. | Adams, Larry D. | Laux, Renee | Song, Yeunjoo | Ogrocki, Paula | Lerner, Alan J. | Vance, Jeffery M. | Haines, Jonathan L. | Scott, William K. | Pericak-Vance, Margaret A. | Cuccaro, Michael L.

Article Type: Research Article

Abstract: Background: Lower education has been reported to be associated with dementia. However, many studies have been done in settings where 12 years of formal education is the standard. Formal schooling in the Old Order Amish communities (OOA) ends at 8th grade which, along with their genetic homogeneity, makes it an interesting population to study the effect of education on cognitive impairment. Objective: The objective of this study was to examine the association of education with cognitive function in individuals from the OOA. We hypothesized that small differences in educational attainment at lower levels of formal education were …associated with risk for cognitive impairment. Methods: Data of 2,426 individuals from the OOA aged 54–99 were analyzed. The Modified Mini-Mental State Examination (3MS-R) was used to classify participants as CI or normal. Individuals were classified into three education categories: <8, 8, and >8 years of education. To measure the association of education with cognitive status, a logistic regression model was performed adding age and sex as covariates. Results: Our results showed that individuals who attained lowest levels of education (<8 and 8) had a higher probability of becoming cognitvely impaired compared with people attending >8 years (OR = 2.96 and 1.85). Conclusion: Even within a setting of low levels of formal education, small differences in educational attainment can still be associated with the risk of cognitive impairment. Given the homogeneity of the OOA, these results are less likely to be biased by differences in socioeconomic backgrounds. Show more

Keywords: Amish, cognitive function, cognitive impairment, dementia, education, logistic regression, Modified Mini-Mental State Examination (3MS)

DOI: 10.3233/JAD-200909

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 451-458, 2021

Authors: Alexopoulos, Panagiotis | Soldatos, Rigas | Kontogianni, Evangelia | Frouda, Maria | loanna Aligianni, Souzana | Skondra, Maria | Passa, Maria | Konstantopoulou, Georgia | Stamouli, Evangelia | Katirtzoglou, Evgenia | Politis, Anastasios | Economou, Polychronis | Alexaki, Maria | Siarkos, Kostas | Politis, Antonios

Article Type: Research Article

Abstract: Background: The outbreak of the COVID-19 pandemic seems to have mental health implications for both people with neurocognitive disorder and their caregivers. Objective: The study aimed to shed light on relations between caregiver mental reaction to the pandemic and caregiver distress related to neuropsychiatric symptoms, memory impairment progression, and functional impairment of people with neurocognitive disorder during the period of confinement in Greece. Methods: The study included caregivers of patients with mild (N = 13) and major (N = 54) neurocognitive disorder. The caregiver-based telephone interview was based on items of the neuropsychiatric inventory questionnaire, the AD8 Dementia Screening Instrument, …and the Bristol Activities of Daily Living Scale. Regarding the mental impact of the COVID-19 crisis on caregivers, four single questions referring to their worries in the last seven days were posed, in addition to the scales Generalized Anxiety Disorder 7-Item (GAD-7) and the 22-item Impact of Event Scale-revised (IES-R). A stepwise linear regression model was employed for studying the relationship between caregiver distress and demographic and clinical data and caregiver mental reaction to COVID-19 pandemic outbreak. Results: Caregiver distress severity during the confinement period was influenced not only by memory deficits (p  = 0.009) and neuropsychiatric symptoms (p  < 0.001) of patients, but also by caregiver hyperarousal (p  = 0.003) and avoidance symptoms (p  = 0.033) and worries directly linked to the COVID-19 crisis (p  = 0.022). Conclusion: These observations provide further evidence for the urgent need for support of caregivers of patients with neurocognitive disorder during the COVID-19 pandemic. Show more

Keywords: Confinement, COVID-19, impairment in activities of daily living, memory deficits, neuropsychiatric symptoms

DOI: 10.3233/JAD-200991

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 459-466, 2021