Journal of Alzheimer's Disease - Volume 81, issue 1

Authors: Ashizawa, Takumi | Igarashi, Ataru | Sakata, Yukinori | Azuma, Mie | Fujimoto, Kenichi | Kobayashi, Tsukasa | Takase, Yoshimasa | Ikeda, Shunya

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) increases societal costs and decreases the activities of daily living (ADL) and quality of life (QoL) of the affected individuals. Objective: We assess the impact of AD severity on ADL, QoL, and caregiving costs in Japanese facilities for the elderly. Methods: Patients with AD in facilities for the elderly were included (47 facilities, N = 3,461). The QoL, ADL, and disease severity of patients were assessed using Barthel Index (BI), EuroQoL-5D-5L (EQ-5D-5L), and Mini-Mental State Examination (MMSE), respectively. Annual caregiving costs were estimated using patients’ claims data. The patients were subcategorized into the following …three groups according to the MMSE score: mild (21≤MMSE≤30), moderate (11≤MMSE≤20), and severe (0≤MMSE≤10). Changes among the three groups were evaluated using the Jonckheere-Terpstra test. Results: Four hundred and one participants were on anti-AD medicines, of whom 287 (age: 86.1±6.4 years, 76.7% women) in the mild (n  = 53, 84.0±6.9 years, 71.7%), moderate (n  = 118, 86.6±5.9 years, 76.3%), and severe (n  = 116, 86.6±6.5 years, 79.3%) groups completed the study questionnaires. The mean BI and EQ-5D-5L scores for each group were 83.6, 65.1, and 32.8 and 0.801, 0.662, and 0.436, respectively. The mean annual caregiving costs were 2.111, 2.470, and 2.809 million JPY, respectively. As AD worsened, the BI and EQ-5D-5L scores decreased and annual caregiving costs increased significantly. Conclusion: AD severity has an impact on QoL, ADL, and caregiving costs. Show more

Keywords: Activities of daily living, Alzheimer’s disease, cost of illness, Japan, observational study, quality of life

DOI: 10.3233/JAD-201514

Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 367-374, 2021

Authors: Wong, Dickson | Broberg, Dana N. | Doad, Jagroop | Umoh, Joseph U. | Bellyou, Miranda | Norley, Chris J. D. | Holdsworth, David W. | Montero-Odasso, Manuel | Beauchet, Olivier | Annweiler, Cedric | Bartha, Robert

Article Type: Research Article

Abstract: Background: Vitamin D deficiency and altered body composition are common in Alzheimer’s disease (AD). Memantine with vitamin D supplementation can protect cortical axons against amyloid-β exposure and glutamate toxicity. Objective: To study the effects of vitamin D deprivation and subsequent treatment with memantine and vitamin D enrichment on whole-body composition using a mouse model of AD. Methods: Male APPswe/PS1dE9 mice were divided into four groups at 2.5 months of age: the control group (n  = 14) was fed a standard diet throughout; the remaining mice were started on a vitamin D-deficient diet at month 6. The vitamin …D-deficient group (n  = 14) remained on the vitamin D-deficient diet for the rest of the study. Of the remaining two groups, one had memantine (n  = 14), while the other had both memantine and 10 IU/g vitamin D (n  = 14), added to their diet at month 9. Serum 25(OH)D levels measured at months 6, 9, 12, and 15 confirmed vitamin D levels were lower in mice on vitamin D-deficient diets and higher in the vitamin D-supplemented mice. Micro-computed tomography was performed at month 15 to determine whole-body composition. Results: In mice deprived of vitamin D, memantine increased bone mineral content (8.7% increase, p  < 0.01) and absolute skeletal tissue mass (9.3% increase, p  < 0.05) and volume (9.2% increase, p  < 0.05) relative to controls. This was not observed when memantine treatment was combined with vitamin D enrichment. Conclusion: Combination treatment of vitamin D and memantine had no negative effects on body composition. Future studies should clarify whether vitamin D status impacts the effects of memantine treatment on bone physiology in people with AD. Show more

Keywords: Adipose tissue, Alzheimer’s disease, animal models, body composition, bone and bones, 3-D imaging, memantine, muscle, vitamin D, x-ray micro-CT

DOI: 10.3233/JAD-201137

Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 375-388, 2021

Authors: Li, Lin-Lin | Ma, Ya-Hui | Bi, Yan-Lin | Sun, Fu-Rong | Hu, Hao | Hou, Xiao-He | Xu, Wei | Shen, Xue-Ning | Dong, Qiang | Tan, Lan | Yang, Jiu-Long | Yu, Jin-Tai

Article Type: Research Article

Abstract: Background: Serum uric acid (SUA) affects the reaction of oxidative stress and free radicals in the neurodegenerative processes. However, whether SUA impacts Alzheimer’s disease (AD) pathology remains unclear. Objective: We aimed to explore whether high SUA levels can aggravate the neurobiological changes of AD in preclinical AD. Methods: We analyzed cognitively intact participants (n = 839, age 62.16 years) who received SUA and cerebrospinal fluid (CSF) biomarkers (amyloid-β [Aβ], total tau [t-Tau], and phosphorylated tau [p-Tau]) measurements from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database using multivariable-adjusted linear models. Results: Levels of …SUA in the preclinical AD elevated compared with the healthy controls (p = 0.007) and subjects with amyloid pathology had higher concentration of SUA than controls (p = 0.017). Roughly, equivalent levels of SUA displayed among cognitively intact individuals with or without tau pathology and neurodegeneration. CSF Aβ1 - 42 (p = 0.019) and Aβ1 - 42 /Aβ1 - 40 (p = 0.027) were decreased and CSF p-Tau/Aβ1 - 42 (p = 0.009) and t-Tau/Aβ1 - 42 (p = 0.043) were increased with the highest (> 75th percentile) SUA when compared to lowest SUA, implying a high burden of cerebral amyloidosis in individuals with high SUA. Sensitivity analyses using the usual threshold to define hyperuricemia and precluding drug effects yielded robust associations. Nevertheless, the quadratic model did not show any U-shaped relationships between them. Conclusion: SUA may aggravate brain amyloid deposition in preclinical AD, which corroborated the detrimental role of SUA. Show more

Keywords: Alzheimer’s disease pathology, biomarkers, cerebrospinal fluid, serum uric acid

DOI: 10.3233/JAD-201192

Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 389-401, 2021

Authors: Miyagawa, Naoko | Ohkubo, Takayoshi | Fujiyoshi, Akira | Shiino, Akihiko | Chen, Randi | Ross, George Webster | Willcox, Bradley | Miura, Katsuyuki | Ueshima, Hirotsugu | Masaki, Kamal

Article Type: Research Article

Abstract: Background: Few studies have compared factors related to cognitive function among people with similar genetic backgrounds but different lifestyles. Objective: We aimed to identify factors related to lower cognitive scores among older Japanese men in two genetically similar cohorts exposed to different lifestyle factors. Methods: This cross-sectional study of community-dwelling Japanese men aged 71–81 years included 2,628 men enrolled in the Kuakini Honolulu-Asia Aging Study based in Hawaii and 349 men in the Shiga Epidemiological Study of Subclinical Atherosclerosis based in Japan. We compared participant performance through Cognitive Abilities Screening Instrument (CASI) assessment in Hawaii (1991–1993) …and Japan (2009–2014). Factors related to low cognitive scores (history of cardiovascular disease, cardiometabolic factors, and lifestyle factors) were identified with questionnaires and measurements. Multivariable logistic regression analysis was used to calculate the adjusted odds ratios (ORs) of a low (< 82) CASI score based on different factors. Results: CASI scores were lower in Hawaii than in Japan [21.2%(n  = 556) versus 12.3%(n  = 43), p  < 0.001], though this was not significant when adjusted for age and educational attainment (Hawaii 20.3%versus Japan 17.9%, p  = 0.328). History of stroke (OR = 1.65, 95%confidence interval = 1.19–2.29) was positively associated with low cognitive scores in Hawaii. Body mass index ≥25 kg/m2 tended to be associated with low cognitive scores in Japan; there was a significant interaction between the cohorts. Conclusion: Cognitive scores differences between cohorts were mostly explained by differences in educational attainment. Conversely, cardiovascular diseases and cardiometabolic factors differentially impacted cognitive scores among genetically similar older men exposed to different lifestyle factors. Show more

Keywords: Aged, cognitive decline, community dwelling, Japanese, Japanese Americans, men

DOI: 10.3233/JAD-201084

Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 403-412, 2021

Authors: Nelson, Monica E. | Andel, Ross | Nedelska, Zuzana | Martinkova, Julie | Cechova, Katerina | Markova, Hana | Matuskova, Veronika | Nikolai, Tomas | Lerch, Ondrej | Parizkova, Martina | Laczo, Jan | Vyhnalek, Martin | Hort, Jakub

Article Type: Research Article

Abstract: Background: Identifying modifiable risk factors for cognitive decline can reduce burden of dementia. Objective: We examined whether homocysteine was associated with memory performance, mediated by entorhinal volume, hippocampal volume, total gray matter volume, or white matter lesions, and moderated by APOE ɛ4 allele, B vitamins, creatinine, total cholesterol, or triglycerides. Methods: All 204 members of the Czech Brain Aging Study with subjective cognitive decline (SCD; n  = 60) or amnestic mild cognitive impairment (aMCI; n  = 144) who had valid data were included. Linear regression was used, followed by conditional process modeling to examine mediation and moderation. …Results: Controlling for age, sex, and education, higher homocysteine was related to poorer memory performance overall (b  = –0.03, SE  = 0.01, p  = 0.017) and in participants with SCD (b  = –0.06, SE  = 0.03, p  = 0.029), but less so in aMCI (b  = –0.03, SE  = 0.02, p  = 0.074); though sensitivity analyses revealed a significant association when sample was reduced to aMCI patients with more complete cognitive data (who were also better functioning; b  = –0.04, SE  = 0.02, p  = 0.022). Results were unchanged in fully adjusted models. Neither mediation by markers of brain integrity nor moderation by APOE ɛ4, B vitamins, creatinine, and cardiovascular factors were significant. Memory sub-analyses revealed that results for SCD were likely driven by non-verbal memory. The homocysteine-memory relationship was significant when hippocampal volume was below the median (b  = –0.04, SE  = 0.02, p  = 0.046), but not at/above the median (p  = 0.247). Conclusion: Higher homocysteine levels may adversely influence memory performance, which appears particularly apparent in those without cognitive impairment. Results appear to be independent of brain health, suggesting that homocysteine may represent a good target for intervention. Show more

Keywords: Hippocampus, magnetic resonance imaging, mild cognitive impairment, neuropsychological tests

DOI: 10.3233/JAD-201558

Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 413-426, 2021