Journal of Alzheimer's Disease - Volume Pre-press, issue Pre-press

Authors: Caselli, Richard J. | Chen, Yinghua | Chen, Kewei | Bauer III, Robert J. | Locke, Dona E.C. | Woodruff, Bryan K.

Article Type: Research Article

Abstract: Background: Older age is a major risk factor for severe COVID-19 disease which has been associated with a variety of neurologic complications, both acutely and chronically. Objective: We sought to determine whether milder COVID-19 disease in older vulnerable individuals is also associated with cognitive and behavioral sequelae. Methods: Neuropsychological, behavioral, and clinical outcomes before and after contracting COVID-19 disease, were compared in members of two ongoing longitudinal studies, the Arizona APOE Cohort and the national Alzheimer’s Disease Research Center (ADRC). Results: 152 APOE and 852 ADRC cohort members, mean age overall roughly 70 years, …responded to a survey that indicated 21 APOE and 57 ADRC members had contracted COVID-19 before their ensuing (post-COVID) study visit. The mean interval between test sessions that preceded and followed COVID was 2.2 years and 1.2 years respectively for the APOE and ADRC cohorts. The magnitude of change between the pre and post COVID test sessions did not differ on any neuropsychological measure in either cohort. There was, however, a greater increase in informant (but not self) reported cognitive change in the APOE cohort (p  = 0.018), but this became nonsignificant after correcting for multiple comparisons. Conclusion: Overall members of both cohorts recovered well despite their greater age-related vulnerability to more severe disease. Show more

Keywords: Alzheimer’s disease, APOE, cognitive aging, COVID-19, mild cognitive impairment

DOI: 10.3233/JAD-220435

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2022

Authors: Gong, Hong-Jian | Tang, Xingyao | Chai, Yin-He | Qiao, Yu-Shun | Xu, Hui | Patel, Ikramulhaq | Zhang, Jin-Yan | Simó, Rafael | Zhou, Jian-Bo

Article Type: Research Article

Abstract: Background: Obesity has been linked to cognitive impairment. However, how changes in body mass index (BMI) over the life course influence cognitive function remains unclear. Objective: The influence of distinct weight-change patterns from young adulthood to midlife and late adulthood on cognitive function in older adults was explored. Methods: A total of 5,809 individuals aged≥60 years were included and categorized into four groups on the basis of BMI change patterns. Cognitive function was assessed using four cognition tests in the baseline survey. The relationship between the weight-change patterns and cognition was evaluated using regression models. …Results: In comparison with participants who remained at non-obese, those moving from the non-obese to obese weight-change pattern from young (25 years of age) to middle adulthood showed lower Digit Symbol Substitution Test (DSST) scores (β= –1.28; 95% confidence interval [CI]: –2.24 to –0.32). A non-obese to obese change pattern from age 25 years of age to 10 years before baseline was associated with a higher risk of DSST impairment (odds ratio = 1.40; 95% CI: 1.09 to 1.79). In comparison with participants whose heaviest weight was recorded after 60 years of age, those with the heaviest weight between 18 and 40 years of age had lower DSST scores (β= –1.46; 95% CI: –2.77 to –1.52). Conclusion: Our results suggest that the transition from the non-obese to obese category in early adulthood and appearance of the heaviest weight between 18 and 40 years of age are associated with lower cognitive function in later life. Show more

Keywords: Body mass index, body weight changes, cognition, overweight

DOI: 10.3233/JAD-220788

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Morys, Filip | Potvin, Olivier | Zeighami, Yashar | Vogel, Jacob | Lamontagne-Caron, Rémi | Duchesne, Simon | Dagher, Alain

Article Type: Research Article

Abstract: Background: Excess weight in adulthood leads to health complications such as diabetes, hypertension, or dyslipidemia. Recently, excess weight has also been related to brain atrophy and cognitive decline. Reports show that obesity is linked with Alzheimer’s disease (AD)-related changes, such as cerebrovascular damage or amyloid-β accumulation. However, to date no research has conducted a direct comparison between brain atrophy patterns in AD and obesity. Objective: Here, we compared patterns of brain atrophy and amyloid-β/tau protein accumulation in obesity and AD using a sample of over 1,300 individuals from four groups: AD patients, healthy controls, obese otherwise healthy individuals, …and lean individuals. Methods: We age- and sex-matched all groups to the AD-patients group and created cortical thickness maps of AD and obesity. This was done by comparing AD patients with healthy controls, and obese individuals with lean individuals. We then compared the AD and obesity maps using correlation analyses and permutation-based tests that account for spatial autocorrelation. Similarly, we compared obesity and AD brain maps with amyloid-β and tau protein maps from other studies. Results: Obesity maps were highly correlated with AD maps but were not correlated with amyloid-β/tau protein maps. This effect was not accounted for by the presence of obesity in the AD group. Conclusion: Our research confirms that obesity-related grey matter atrophy resembles that of AD. Excess weight management could lead to improved health outcomes, slow down cognitive decline in aging, and lower the risk for AD. Show more

Keywords: Alzheimer’s disease, grey matter, neurodegeneration, obesity

DOI: 10.3233/JAD-220535

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Sakai, Kenji | Noguchi-Shinohara, Moeko | Tanaka, Hidetomo | Ikeda, Tokuhei | Hamaguchi, Tsuyoshi | Kakita, Akiyoshi | Yamada, Masahito | Ono, Kenjiro

Article Type: Research Article

Abstract: Background: Cerebrospinal fluid (CSF) biomarkers in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri) have demonstrated inconsistent results. Objective: We investigated the relationship between CSF amyloid-β protein (Aβ) and vascular pathological findings to elucidate the mechanisms of Aβ elimination from the brain in CAA-ri. Methods: We examined Aβ 40 and Aβ 42 levels in CSF samples in 15 patients with CAA-ri and 15 patients with Alzheimer’s disease and cerebral amyloid angiopathy (AD-CAA) using ELISA as a cross-sectional study. Furthermore, we pathologically examined Aβ 40 and Aβ 42 depositions on the leptomeningeal blood vessels …(arteries, arterioles, and veins) using brain biopsy samples from six patients with acute CAA-ri and brain tissues of two autopsied patients with CAA-ri. Results: The median Aβ40 and Aβ42 levels in the CSF showed no significant difference between pre-treatment CAA-ri (Aβ40, 6837 pg/ml; Aβ42 , 324 pg/ml) and AD-CAA (Aβ40 , 7669 pg/ml, p  = 0.345; Aβ42 , 355 pg/ml, p  = 0.760). Aβ40 and Aβ42 levels in patients with post-treatment CAA-ri (Aβ40, 1770 pg/ml, p  = 0.056; Aβ42 , 167 pg/ml, p  = 0.006) were lower than those in patients with pre-treatment CAA-ri. Regarding Aβ40 and Aβ42 positive arteries, acute CAA-ri cases showed a higher frequency of partially Aβ-deposited blood vessels than postmortem CAA-ri cases (Aβ40 , 20.8% versus 3.9%, p  = 0.0714; Aβ42 , 27.4% versus 2.0%, p  = 0.0714, respectively). Conclusion: Lower levels of CSF Aβ40 and Aβ42 could be biomarkers for the cessation of inflammation in CAA-ri reflecting the recovery of the intramural periarterial drainage pathway and vascular function. Show more

Keywords: Amyloid-β protein-related angiitis, amyloid-related imaging abnormalities, biomarker, cerebral amyloid angiopathy-related inflammation, cerebrospinal fluid, diagnosis, elimination, pathology, vasculitis

DOI: 10.3233/JAD-220838

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Fleming, Victoria | Helsel, Brian C. | Ptomey, Lauren T. | Rosas, H. Diana | Handen, Benjamin | Laymon, Charles | Christian, Bradley T. | Head, Elizabeth | Mapstone, Mark | Lai, Florence | Krinsky-McHale, Sharon | Zaman, Shahid | Ances, Beau M. | Lee, Joseph H. | Hartley, Sigan L.

Article Type: Research Article

Abstract: Background: Virtually all adults with Down syndrome (DS) develop Alzheimer’s disease (AD) pathology, but research gaps remain in understanding early signs of AD in DS. Objective: The goal of the present study was to determine if unintentional weight loss is part of AD in DS. The specific aims were to: 1) examine relation between chronological age, weight, AD pathology, and AD-related cognitive decline were assessed in a large cohort of adults with DS, and 2) determine if baseline PET amyloid-β (Aβ) and tau PET status (–versus+) and/or decline in memory and mental status were associated with weight loss …prior to AD progression. Methods: Analyses included 261 adults with DS. PET data were acquired using [11 C] PiB for Aβ and [18 F] AV-1451 for tau. Body mass index (BMI) was calculated from weight and height. Direct measures assessed dementia and memory. Clinical AD status was determined using a case consensus process. Percent weight decline across 16–20 months was assessed in a subset of participants (n  = 77). Results: Polynomial regressions indicated an 0.23 kg/m2 decrease in BMI per year beginning at age 36.5 years, which occurs alongside the period during which Aβ and tau increase and memory and mental status decline. At a within-person level, elevated Aβ, decline in memory and mental status were associated with higher percent weight loss across 16–20 months. Conclusion: Unintentional weight loss occurs alongside Aβ deposition and prior to onset of AD dementia, and thus may be a useful sign of AD in DS. Show more

Keywords: Alzheimer’s disease, amyloid, biomarkers, body mass index, tau, weight

DOI: 10.3233/JAD-220865

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: Downer, Brian | Li, Chih-Ying | Al Snih, Soham

Article Type: Research Article

Abstract: Background: Evidence from predominately non-Hispanic White populations indicates that emergency room (ER) admissions and hospitalizations by older adults with and without dementia are associated with caregiver stress and depressive symptoms. These results may not generalize to Hispanic populations because of cultural differences in caregiving roles, responsibilities, and perspectives about care burden. Objective: Investigate the association between ER admissions and hospitalizations by Mexican American older adults with and without dementia and symptoms of depression and stress among family caregivers. Methods: Data came from the 2010/11 wave of the Hispanic Established Populations for the Epidemiologic Study of the …Elderly and Medicare claims files. The final sample included 326 older adults and their caregivers. Negative binomial regression was used to model the association between hospitalizations and ER admissions by older adults in the previous two years and caregivers’ depressive symptoms and stress in 2010/11. Results: The number of older adult ER admissions and hospitalizations was not associated with caregiver depressive symptoms. Two or more ER admissions (incident rate ratio [IRR] = 1.26, 95% CI = 1.05–1.51) and two or more hospitalizations (IRR = 1.32, 95% CI = 1.07–1.61) were associated with significantly higher caregiver stress. Additionally, ER admissions and hospitalizations for a circulatory disease or injury and poisoning were associated with significantly higher caregiver stress. These associations were not modified by the care recipient’s dementia status. Conclusion: Hospitalizations and ER admissions by older Mexican Americans were associated with greater caregiver stress but not depressive symptoms. These associations were similar for caregivers to older adults with and without dementia. Show more

Keywords: Caregivers, dementia, health services, Mexican Americans

DOI: 10.3233/JAD-220997

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Deng, Xiaoli | Geng, Zhao | Yu, Juan | Dai, Xiaoyan | Kuang, Xunjie | Chen, Xia | Li, Ruifeng | Liu, Ting | Li, Chongyi

Article Type: Research Article

Abstract: Background: The association between cataracts and cognitive functions has been reported in several studies. However, the dynamic trajectories of cognitive changes in patients with cataracts remain unelucidated. Objective: The aim of the study was to evaluate the dynamic trajectories of cognitive changes in patients with cataracts. Methods: This observational cohort study recruited 1,146 patients with age-related cataracts (ARC) from the Department of Ophthalmology, Daping Hospital, from September 2020 to November 2021. The cognitive functions of the patients were assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) test at baseline and 6 …months of follow-up. The trajectories and the associated risk factors for the longitudinal cognitive decline during the 6-month follow-up were investigated. Results: Patients with severe ARC [median (IQR): 0 month, 24 (22, 25); 6 months, 23 (21,25)] had lower TICS-40 scores than those with non-severe ARC [0 month, 31 (24, 33), p  <  0.001; 6 months, 31 (23,33), p  <  0.001] and controls [0 month, 32 (28, 35), p  <  0.001; 6 months, 32 (28, 35), p  <  0.001] at both baseline and 6 months of follow-up. Age (OR: 1.311, 95% CI: 1.229 to 1.398) and cataract grade (OR: 5.569, 95% CI: 2.337 to 13.273) were found to be the risk factors of cognitive decline as indicated by a decrease in the TICS-40 scores. Conclusion: ARC is associated with an increased risk of longitudinal cognitive decline; however, the reversibility of such declines needs to be investigated further. Show more

Keywords: Age, cataract, cataract grade, cognitive decline, risk factor

DOI: 10.3233/JAD-220963

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2022

Authors: Jia, Jianping | Zhang, Yue | Shi, Yuqing | Yin, Xuping | Wang, Shiyuan | Li, Yan | Zhao, Tan | Liu, Wenying | Zhou, Aihong | Jia, Longfei

Article Type: Short Communication

Abstract: Alzheimer’s disease (AD) primarily affects older adults. In this report, we present the case of a 19-year-old male with gradual memory decline for 2 years and World Health Organization-University of California Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT) results also showing memory impairment. Positron emission tomography-magnetic resonance imaging with 18 F fluorodeoxyglucose revealed atrophy of the bilateral hippocampus and hypometabolism in the bilateral temporal lobe. Examination of the patient’s cerebrospinal fluid showed an increased concentration of p-tau181 and a decreased amyloid-β 42/40 ratio. However, through whole-genome sequencing, no known gene mutations were identified. Considering the above, the patient was …diagnosed with probable AD. Show more

Keywords: Case report, early-onset Alzheimer’s disease, gene mutation, hippocampal atrophy, memory impairment

DOI: 10.3233/JAD-221065

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-8, 2022

Authors: Zhào, Hóngyi | Wei, Wei | Xie, Hongyang | Huang, Yonghua

Article Type: Short Communication

Abstract: Brain aging is characterized by the declines in motor and cognitive features. The present study is to detect motor cognitive risk syndrome (MCRS) in older adults with white matter lesions (WML). 134 WML aged patients were recruited and diagnosed with the criteria for MCRS. Numerous cognitive function tests and walking tests were performed. The frequency of MCRS is 28.35% . Verbal fluency test, Mini-Mental State Examination, and dual-task walking speed were independent risk factor of MCRS. These findings indicated that MCRS was common in WML seniors. MCRS was associated with the pathologies of WML in older adults.

Keywords: Aging, cerebral small vessel disease, dual-task walking, magnetic resonance imaging, motoric cognitive risk syndrome, white matter lesions

DOI: 10.3233/JAD-220712

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-7, 2022

Authors: Schäfer, Simona | Mallick, Elisa | Schwed, Louisa | König, Alexandra | Zhao, Jian | Linz, Nicklas | Bodin, Timothy Hadarsson | Skoog, Johan | Possemis, Nina | ter Huurne, Daphne | Zettergren, Anna | Kern, Silke | Sacuiu, Simona | Ramakers, Inez | Skoog, Ingmar | Tröger, Johannes

Article Type: Research Article

Abstract: Background: Modern prodromal Alzheimer’s disease (AD) clinical trials might extend outreach to a general population, causing high screen-out rates and thereby increasing study time and costs. Thus, screening tools that cost-effectively detect mild cognitive impairment (MCI) at scale are needed. Objective: Develop a screening algorithm that can differentiate between healthy and MCI participants in different clinically relevant populations. Methods: Two screening algorithms based on the remote ki:e speech biomarker for cognition (ki:e SB-C) were designed on a Dutch memory clinic cohort (N  = 121) and a Swedish birth cohort (N  = 404). MCI classification was each evaluated on …the training cohort as well as across on the unrelated validation cohort. Results: The algorithms achieved a performance of AUC  0.73 and AUC  0.77 in the respective training cohorts and AUC  0.81 in the unseen validation cohort. Conclusion: The results indicate that a ki:e SB-C based algorithm robustly detects MCI across different cohorts and languages, which has the potential to make current trials more efficient and improve future primary health care. Show more

Keywords: Alzheimer’s disease, biomarker, clinical trial, machine learning, mild cognitive impairment, screening

DOI: 10.3233/JAD-220762

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-7, 2022