Journal of Alzheimer's Disease - Volume 89, issue 2

Authors: Omaña, Humberto | Madou, Edward | Hunter, Susan W.

Article Type: Short Communication

Abstract: In people with dementia, provision of mobility aids is standard treatment for those with impaired gait. However, mobility aid use is independently associated with increased falls risk. In this short communication, gait velocity and stride time variability were recorded in eleven adults with Alzheimer’s disease dementia. Three conditions were tested: single-task (no aid), walking with a walker, and dual-task (walker use and counting backwards) under both a straight path and Figure-of-8 walking configuration. Gait velocity increased when using a walker compared to no aid in the Figure-of-8 walking configuration. Walker use improved gait in simple walking, but benefits diminished upon …dual-task. Show more

Keywords: Alzheimer’s disease, assistive devices, gait, multitasking behavior, walkers

DOI: 10.3233/JAD-220331

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 399-404, 2022

Authors: Russo, Mirella | Santilli, Matteo | De Rosa, Matteo A. | Calisi, Dario | Dono, Fedele | Mattoli, Maria Vittoria | Bonanni, Laura | Onofrj, Marco | Sensi, Stefano L.

Article Type: Short Communication

Abstract: A 43-year-old came to our observation for progressive cognitive impairment, confirmed by the neuropsychological evaluation. A diagnosis of multidomain amnestic mild cognitive impairment, due to unknown reasons, was posited at the first assessment. The patient’s neurological exam was otherwise completely normal. The patient’s mother was clinically diagnosed with frontotemporal dementia in her forties. The patient underwent neuroimaging investigations and cerebrospinal fluid analysis. Our diagnostic work-up pointed toward a neurodegenerative etiology, but the presence of concurrent cardiomyopathy emerged in the meantime. Due to the patient’s family history, a thorough genetic screening was performed. The results revealed a unique genetic asset, with …heterozygotic variants of three amyloid-related genes (PSEN1 , APP , and MYBPC3 ). PSEN1 and MYBPC3 mutations showed distinct pathogenic features and accounted for the patient’s brain and cardiac amyloidosis, whereas the APP variant was of uncertain pathological implications. Show more

Keywords: cardiomyopathy, early onset dementia, mild cognitive impairment, neurodegeneration

DOI: 10.3233/JAD-220528

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 405-410, 2022

Authors: Wang, Lindsey | Davis, Pamela B. | Volkow, Nora D. | Berger, Nathan A. | Kaelber, David C. | Xu, Rong

Article Type: Short Communication

Abstract: An infectious etiology of Alzheimer’s disease has been postulated for decades. It remains unknown whether SARS-CoV-2 viral infection is associated with increased risk for Alzheimer’s disease. In this retrospective cohort study of 6,245,282 older adults (age ≥65 years) who had medical encounters between 2/2020–5/2021, we show that people with COVID-19 were at significantly increased risk for new diagnosis of Alzheimer’s disease within 360 days after the initial COVID-19 diagnosis (hazard ratio or HR:1.69, 95% CI: 1.53–1.72), especially in people age ≥85 years and in women. Our findings call for research to understand the underlying mechanisms and for continuous surveillance of …long-term impacts of COVID-19 on Alzheimer’s disease. Show more

Keywords: Alzheimer’s disease, COVID-19, electronic health records, viral etiology

DOI: 10.3233/JAD-220717

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 411-414, 2022

Authors: Goodman, Zachary T. | Banerjee, Nikhil | Rooks, Joshua | McInerney, Katalina | Sun, Xiaoyan | Getz, Sarah | Kaur, Sonya | Sun-Suslow, Ni | Junco, Barbara | Levin, Bonnie E.

Article Type: Research Article

Abstract: Background: Frailty is directly linked to physical robustness and cognitive decline in older age. The Fried Frailty phenotype (FP) is a construct composed of five core symptoms that has been studied predominately in older age. There is little research contrasting the psychometric properties of the FP in mid-life versus older age. Objective: We compared the psychometric properties of the FP in mid-life and older age and investigated relationships between the FP and cognition. Methods: Frailty and neuropsychological assessments were completed on 361 adults, between 45 and 92 years of age, without primary neurological disorders. Confirmatory factor …analysis was used to examine FP, indicated by Grip Strength, Gait Speed, Physical Activity, Fatigue, and Weight Loss. Measurement invariance was tested in mid-life (45–64 years) versus older age (≥65 years). Associations were examined between FP and language, executive functions, memory, processing speed, and visuospatial domains as well as a Generalized Cognition factor. Age was tested as a moderator of these associations. Results: Weight Loss was a poor indicator of FP. Factor loadings were comparable across age groups; however, Fatigue was disproportionately higher among those in mid-life. FP was negatively associated with all cognitive domains and remained invariant across age groups. Conclusion: Results support the construct validity of the FP and document its stable associations with poorer cognition in middle and older life. Future research investigating central features of frailty earlier in life may offer avenues for developing targeted prevention measures and better characterization of individuals with elevated dementia risk. Show more

Keywords: Aging, cognition, confirmatory factor analysis, frailty, measurement invariance, neuropsychology, quantitative methods

DOI: 10.3233/JAD-215475

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 415-426, 2022

Authors: Yang, Jiajia | Deng, Yan | Yan, He | Li, Benchao | Wang, Ziping | Liao, Jingling | Cai, Xiaoli | Zhou, Li | Tan, Wei | Rong, Shuang

Article Type: Research Article

Abstract: Background: The relationship between grip strength and cognitive function remains no consensus in the older adults. Objective: To investigate the association of grip strength with cognitive function and cognitive performance in different domains. Methods: Participants of the present cross-sectional study were from the National Health and Nutrition Examination Survey 2011-2014. Grip strength was measured by grip dynamometer, and combined handgrip strength was the sum of the largest reading from each hand. Four cognitive domains (immediate and delayed memory, language, and attention) were assessed by a set of neuropsychological tests. The subjective cognitive decline was determined via …self-report. Results: Among 2,618 participants, combined grip strength was positively associated with scores on global cognitive function and each cognitive domain after controlling for demographic characteristics, lifestyle factors, and history of disease. In addition, compared to those with grip strength < 46.7 kg, participants with grip strength≥75.3 kg had odds ratios of 0.36 (95% CI: 0.21 to 0.63) for poor global cognitive function, 0.66 (95% CI: 0.38 to 1.13) for poor immediate memory, 0.53 (95% CI: 0.30 to 0.93) for poor delayed memory, 0.48 (95% CI: 0.27 to 0.86) for poor language function, 0.20 (95% CI: 0.11 to 0.35) for poor attention, and 0.36 (95% CI: 0.18 to 0.73) for subjective cognitive decline in fully adjusted model. Conclusion: Older adults with higher grip strength were significantly associated with better performance on cognition function included global and various domains such as memory, language, attention, and subjective cognitive decline. Show more

Keywords: Cognitive function, cross-sectional study, grip strength, old adults

DOI: 10.3233/JAD-215454

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 427-436, 2022

Authors: Rundek, Tatjana | Del Brutto, Victor J. | Goryawala, Mohammed | Dong, Chuanhui | Agudelo, Christian | Saporta, Anita Seixas | Merritt, Stacy | Camargo, Christian | Ariko, Taylor | Loewenstein, David A. | Duara, Ranjan | Haq, Ihtsham

Article Type: Research Article

Abstract: Background: Perivascular spaces (PVS) are fluid-filled compartments surrounding small intracerebral vessels that transport fluid and clear waste. Objective: We examined associations between PVS count, vascular and neurodegenerative risk factors, and cognitive status among the predominantly Hispanic participants of the FL-VIP Study of Alzheimer’s Disease Risk. Methods: Using brain MRI (n  = 228), we counted PVS in single axial image through the basal ganglia (BG) and centrum semiovale (CSO). PVS per region were scored as 0 (none), 1 (<10), 2 (11–20), 3 (21–40), and 4 (>40). Generalized linear models examined PVS associations with vascular risk factors and a …composite vascular comorbidity risk (VASCom) score. Results: Our sample (mean age 72±8 years, 61% women, 60% Hispanic, mean education 15±4 years, 33% APOE4 carriers) was 59% hypertensive, 21% diabetic, 66% hypercholesteremic, and 30% obese. Mean VASCom score was 2.3±1.6. PVS scores ranged from 0–4 in the BG (mean 1.3±0.7) and CSO (mean 1.2±0.9), and 0–7 combined (mean 2.5±1.4). In multivariable regression models, BG PVS was associated with age (β= 0.03/year, p  < 0.0001), Hispanic ethnicity (β= 0.29, p  = 0.01), education (β= 0.04/year, p  = 0.04), and coronary bypass surgery (β= 0.93, p  = 0.02). CSO PVS only associated with age (β= 0.03/year, p  < 0.01). APOE4 and amyloid-β were not associated with PVS. Conclusion: BG PVS may be a marker of subclinical cerebrovascular disease. Further research is needed to validate associations and identify mechanisms linking BG PVS and cerebrovascular disease markers. PVS may be a marker of neurodegeneration despite our negative preliminary findings and more research is warranted. The association between BG PVS and Hispanic ethnicity also requires further investigation. Show more

Keywords: Basal ganglia, brain MRI, centrum semiovale, perivascular spaces, vascular risk factors

DOI: 10.3233/JAD-215585

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 437-448, 2022

Authors: Lissek, Vanessa J. | Ben Abdallah, Heithem | Praetorius, Arthur | Ohmann, Tobias | Suchan, Boris

Article Type: Research Article

Abstract: Background: While cognitive interventions in mild cognitive impairment (MCI) show positive effects on cognitive performance, physical activity appear to slow down cognitive decline, suggesting a relationship between both factors. However, previous combined programs that have shown significant improvement in cognitive function in MCI have typically trained cognition and physical functioning separately. Objective: This project aimed at evaluating two group interventions combining the stimulation of physical and cognitive domains in individuals with MCI: Simultaneous stimulation of physical and cognitive skills in comparison to a standardized training, which stimulates cognitive and physical functions separately. Methods: The study was …designed as a randomized controlled trial. The first group was trained on the SpeedCourt® system while the second group completed the standardized Fitfor100 program. Training was completed by a total of 39 subjects with diagnosed MCI as determined by the CERAD (SpeedCourt®: 24 subjects, Fitfor100:15 individuals). Results: There were significant improvements of physical factors (e.g., hand strength and balance) in both groups. Improvement in the CERAD total score allowed for a post interventional classification of all participants into non-MCI and MCI. This effect persisted over a period of three months. Both forms of intervention were found to be effective in improving various cognitive functions which persisted for a period of three months. Conclusion: Both evaluated non-pharmacological, multicomponent interventions, which combined physical and cognitive training in a social setting showed improvement of cognitive functions leading to a persistent classification of former MCI patients in non-MCI patients. Show more

Keywords: Cognitive training, mild cognitive impairment, multi- component intervention, physiological intervention, simultaneous stimulation of physical and cognitive abilities

DOI: 10.3233/JAD-220145

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 449-462, 2022

Authors: Matti, Nathalie | Javanshiri, Keivan | Haglund, Mattias | Saenz-Sardá, Xavier | Englund, Elisabet

Article Type: Research Article

Abstract: Background: There are few studies on the locus coeruleus (LC) in frontotemporal lobar degeneration (FTLD) and the potential differences in the LC related to the underlying proteinopathy. Objective: The aim of this study was to investigate the LC in FTLD subgroups. Methods: Neuropathological cases diagnosed with FTLD were included. The subgroups consisted of FTLD with tau, transactive response DNA-binding protein 43 (TDP) and fused in sarcoma (FUS). Micro- and macroscopical degeneration of the LC were assessed with respect to the number of neurons and the degree of depigmentation. A group of cognitively healthy subjects and a …group with vascular cognitive impairment (VCI) served as comparison groups. Results: A total of 85 FTLD cases were included, of which 44 had FTLD-TDP, 38 had FTLD-tau, and three had FTLD-FUS. The groups were compared with 25 VCI cases and 41 cognitively healthy control cases (N  = 151 for the entire study). All FTLD groups had a statistically higher microscopical degeneration of the LC compared to the controls, but the FTLD-tau group had greater micro- and macroscopical degeneration than the FTLD-TDP group. Age correlated positively with the LC score in the FTLD-tau group, but not in the FTLD-TDP group. Conclusion: A greater microscopical degeneration of the LC was observed in all FTLD cases compared to healthy controls and those with VCI. The LC degeneration was more severe in FTLD-tau than in FTLD-TDP. The macroscopically differential degeneration of the LC in FTLD subgroups may facilitate differential diagnostics, potentially with imaging. Show more

Keywords: Frontotemporal dementia, locus coeruleus, neuronal counts, tau, tauopathy, TDP-43

DOI: 10.3233/JAD-220276

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 463-471, 2022

Authors: McGrath, Ryan | Robinson-Lane, Sheria G. | Klawitter, Lukus | Rhee, Yeong | Hamm, Jeremy M. | McCourt, Mark E. | Parker, Kelly | Hackney, Kyle J.

Article Type: Research Article

Abstract: Background: Older adults with a cognitive impairment, including those not yet diagnosed, may have deficits in their physical function. Objective: We sought to determine the associations of cognitive impairment consistent with dementia (CICD) diagnosis status on handgrip strength, gait speed, and functional disability in older adults. Methods: The analytical sample included 8,383 adults aged ≥65-years without history of stroke, cancers, neurological conditions, or brain damage who participated in at least one-wave of the 2010–2016 waves of the Health and Retirement Study. A handgrip dynamometer measured handgrip strength. Men with handgrip strength <26 kg and women <16 kg were …weak. Gait speed was timed across a 2.5-m course and those with slowness had gait speed <0.8 m/s. Participants with difficulty or an inability in completing any basic activities of daily living had a functional disability. The adapted Telephone Interview of Cognitive Status evaluated cognitive function. Persons with scores <7 had a CICD. Healthcare provider dementia-related diagnosis was self-reported. Undiagnosed CICD was defined as no reported dementia-related diagnosis but had CICD, while diagnosed CICD was classified as reporting a dementia-related diagnosis. Covariate-adjusted logistic models were used for the analyses. Results: Persons with undiagnosed CICD had 1.37 (95% confidence interval (CI): 1.04–1.80) greater odds for weakness and 2.02 (CI: 1.39–2.94) greater odds for slow gait speed. Older adults with diagnosed CICD had 2.29 (CI: 1.32–3.97) greater odds for slowness and 1.85 (CI: 1.19–2.90) greater odds for functional disability. Conclusion: Screening for CICD could be recommended when defects in physical function are observed in older adults. Show more

Keywords: Activities of daily living, aging, cognitive dysfunction, geriatric assessment, geriatrics, hand strength, walking speed

DOI: 10.3233/JAD-220257

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 473-482, 2022

Authors: Zhong, Shuang | Zhao, Bing | Ma, Ya-Hui | Sun, Yan | Zhao, Yong-Li | Liu, Wen-Hui | Ou, Ya-Nan | Dong, Qiang | Tan, Lan | Yu, Jin-Tai

Article Type: Research Article

Abstract: Background: The associations of physical activity with Alzheimer’s disease (AD) pathologies remain controversial. Objective: To quantitatively assess the association between the frequency of physical activity with cerebrospinal fluid (CSF) biomarkers in AD and further explore the mechanism by which AD pathologies regulate the correlation between physical activity and cognition. Methods: A total of 918 participants without dementia from Chinese Alzheimer’s Biomarker and Lifestyle (CABLE) were examined in this population-based cross-sectional study. Multiple linear models were used to evaluate the associations of physical activity with CSF biomarkers and cognition. Moreover, mediation analyses were conducted to investigate the …potential relationships between physical activity, AD pathologies, and cognitive function. Results: Regular physical activity was positively associated with CSF Aβ42 (p  < 0.001) and Aβ42/40 (p  < 0.001), while it was negatively associated with p-tau/Aβ42 (p  < 0.001) and t-tau/Aβ42 (p  < 0.001). Of all participants, regular physical activity was associated with increased cognitive function (p  < 0.001). The interaction effect indicated that age moderated the association between physical activity frequency and CSF Aβ42 (p  = 0.014) and p-tau/Aβ42 (p  = 0.041). The impact of physical activity on cognition was mediated in part by amyloid pathologies, accounting for 4.87% to 21.56% of the total effect (p  < 0.05). Conclusion: This study showed the beneficial impact of physical activity on AD pathologies and cognition in participants without dementia. Show more

Keywords: Alzheimer’s disease, biomarkers, cerebrospinal fluid, cognition, physical activity

DOI: 10.3233/JAD-220389

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 483-492, 2022