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

Authors: Tongsiri, Sirinart | Levkoff, Sue | Gallagher-Thompson, Dolores | Teri, Linda | Hinton, Ladson | Wisetpholchai, Bussabong | Chuengsatiansup, Komatra | Sihapark, Siranee | Fritz, Stacy | Chen, Hongtu

Article Type: Research Article

Abstract: Background: The Reducing Disability in Alzheimer’s Disease (RDAD) program is an evidence-based intervention found to be feasible for implementation in community settings in the United States, and effective in reducing depression, one of the major behavioral and psychological symptoms of dementia (BPSD). Objective: The goal of the study is to culturally adapt the RDAD for persons with dementia living in community settings of Thailand. Methods: Key adaptation steps included: 1) assess the community, 2) understand/select the intervention, 3) consult with experts/stakeholders, 4) decide what needs to be adapted, 5) adapt the original program, 6) train staff, …and 7) pilot test the adapted materials. Results: Modifications to the original RDAD protocol included changes in number of sessions, mode of delivery, and the specific pleasant activities targeted. The pilot test demonstrated the feasibility and acceptance of the adapted RDAD intervention protocol. Implementers were able to comprehend and implement the core components of the intervention, while family members demonstrated ability to follow instructions, gain knowledge about dementia, and improve skills for setting up realistic goals. Conclusion: Following the key adaptation steps outlined above, we were able to successfully modify the RDAD for the Thai cultural context, maintaining core components of the original protocol. Program implementers demonstrated their ability to supervise family caregivers and help them gain the knowledge and skills needed to provide care for older adults with dementia. Findings from the pilot studies were incorporated into final training and intervention protocols currently being implemented and evaluated in a randomized implementation trial in Thailand. Show more

Keywords: Behavioral and psychological symptoms of dementia, care provision, cultural adaptation, dementia, depression, family caregivers, reducing disability in Alzheimer’s Disease

DOI: 10.3233/JAD-215253

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

Authors: Bommarito, Giulia | Garibotto, Valentina | Frisoni, Giovanni B. | Ribaldi, Federica | Stampacchia, Sara | Assal, Frédéric | Armand, Stéphane | Allali, Gilles | Griffa, Alessandra

Article Type: Short Communication

Abstract: A cross-sectional pilot study to explore the biological substrate of the Motoric Cognitive Risk (MCR) syndrome in a Memory Clinic cohort, using a multimodal imaging approach, was conducted. Twenty participants were recruited and classified as MCR+/−. Amyloid- and tau-PET uptakes, temporal atrophy, white matter hyperintensities, lateral ventricular volume (LVV), and diffusion tensor parameters were compared between groups. No significant differences were found in imaging features related to Alzheimer’s disease or gross vascular damage. MCR+ patients had increased LVV and altered diffusion parameters in the superior corona radiata. Ventricular enlargement and microstructural damage of the surrounding white matter tracts could contribute …to MCR pathophysiology. Show more

Keywords: Alzheimer’s disease, diffusion MRI, gait disorder, lateral ventricles, vascular dementia

DOI: 10.3233/JAD-215461

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

Authors: Zhao, Xing | Du, Wenying | Jiang, Jiehui | Han, Ying

Article Type: Research Article

Abstract: Background: Sleep appears to be a sensitive biomarker that facilitates early detection and effective intervention for Alzheimer’s disease, while subjective cognitive decline (SCD) is a risk factor for Alzheimer’s disease. Prefrontal cortex atrophy is associated with both sleep disruption and cognitive decline. Transcranial brain photobiomodulation (PBM) therapy can enhance frontal cortex oxygen consumption, increasing frontal cortex mediated memory function. Objective: This study aimed to test whether PBM therapy targeting the frontal cortex could improve sleep and cognitive function in SCD. Methods: Fifty-eight SCDs were divided into the PBM group (N  = 32) in which real light therapy …was administered and a sham light therapy group (N  = 26). All the participants received either real light or sham light therapy for 6 days consecutively, while the sleep data were recorded. The n-back task was employed to measure each participant’s working memory. Results: We found no differences in sleep efficiency change (F  = 211, p  = 0.279), REM stage percent change (F  = 420, p  = 0.91), and wake-up time (F  = 212, p  = 0.277) between the two groups. The sleep efficiency and REM were improved within the true light group on the fifth day. The true light group perform better than the control group in the n-back test, the accuracy was higher in the 2-back test (88.6% versus 79.6%, p  = 0.001), and the reaction time in 1-back was shorter (544.80±202.00 versus 592.87±222.05, p  = 0.003). Conclusion: After five days of PBM therapy targeting the prefrontal cortex, sleep efficiency and N-back cognitive performance were improved on the fifth day. Show more

Keywords: Alzheimer’s disease, photobiomodulation, sleep, subjective cognitive decline

DOI: 10.3233/JAD-215715

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

Authors: Sun, Mengzi | Wang, Ling | Guo, Yinpei | Yan, Shoumeng | Li, Jing | Wang, Xuhan | Li, Xiaotong | Li, Bo

Article Type: Research Article

Abstract: Background: Dietary inflammatory index (DII) was associated with Type 2 diabetes mellitus and cognitive function impairment (CFI). Objective: The aim of this study was to explore whether the associations among DII, glycohemoglobin (HbA1c), and CFI were similar in the participants with or without diabetes. Methods: A total of 1,198 participants aged 60 and over from the National Health and Nutrition Examination Survey (NHANES) in 2011–2014 were involved in this study, dividing into subgroups as diabetes and non-diabetes for further analysis. Results: We found that participants with pro-inflammatory diet had higher proportion of CFI patients …(p  <  0.05). Pro-inflammatory diet and HbA1c were positively associated with the risk of CFI; participants with pro-inflammatory diet was 1.479 times on occurrence of CFI compared with anti-inflammatory diet group. The interaction between inflammatory diet and HbA1c was positive on the risk of CFI and was negative on the CERAD-immediate and CERAD-delayed, respectively. Among the participants without diabetes, the associations of Energy-adjusted DII (E-DII) with Animal Fluency test and Digit Symbol Substitution Test (DSST) were partially mediated by HbA1c, and the mediated proportion was 5.8% and 6.6%, respectively. However, there was no such mediation effect in the diabetes patients. Conclusion: In elderly participants without diabetes, there was an interaction between inflammatory diet and HbA1c on the association with CFI, especially for the dimension of CERAD-immediate and CERAD-delayed. Besides, the associations of E-DII with Animal Fluency test and DSST were partially mediated by HbA1c. For diabetic patients, HbA1c, rather than the inflammatory diet has a positive effect on the CFI risk. Show more

Keywords: Cognitive function, diabetes, energy-adjusted dietary inflammatory index, HbA1c, inflammatory diet

DOI: 10.3233/JAD-215688

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

Authors: Leng, Fangda | Zhan, Zhenying | Sun, Yunchuang | Liu, Fang | Edison, Paul | Sun, Yongan | Wang, Zhaoxia | on behalf of Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Recently it has been proposed that microglial response has a stage-dependent effect on the progression of Alzheimer’s disease (AD). Cerebrospinal fluid (CSF) sTREM2 has emerged as a promising microglial activation marker. Objective: To test the stage-dependent role of microglia by studying the association between baseline sTREM2 and dynamic brain structural changes in AD and mild cognitive impairment (MCI) patients. Methods: 22 amyloid-β-positive (A+) and tau-positive (T+) AD and 24 A+T+MCI patients were identified from the Alzheimer’s Disease Neuroimaging Initiative. The patients had baseline CSF amyloid-β, phosphorylated-tau, and sTREM2, and were followed up for at least …one year by T1-weighted and diffusion tensor imaging scans. Gray matter volumes and white matter microstructural integrity were evaluated. Linear mixed models were applied to analyze how baseline sTREM2 may influence the rate of brain structural changes while adjusting for the effects of age, APOE4 status, and the CSF core markers. Results: In A+T+AD patients, baseline CSF sTREM2 was associated with faster mean diffusivity increase in the bilateral posterior corona radiata and right superior longitudinal fasciculus. In A+T+MCI patients, baseline CSF sTREM2 was associated slower gray matter volumetric loss in parahippocampal gyrus, left fusiform cortex, left middle temporal gyrus, and left lateral occipital cortex. Baseline CSF sTREM2 also had a protective effect against mean diffusivity increase in right inferior fronto-occipital fasciculus, left superior longitudinal fasciculus, left forceps minor, and left uncinate fasciculus. Conclusion: Microglial activation at early stage might have a protective effect against neurodegeneration, while at late stage it might facilitate AD. Future efforts on modulating microglial activation could be promising, given a carefully selected time window for intervention. Show more

Keywords: Alzheimer’s disease, diffusion tensor imaging, disease progression, microglial activation, sTREM2, voxel-based morphometry

DOI: 10.3233/JAD-220102

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

Authors: Dong, Liling | Liu, Caiyan | Sha, Longze | Mao, Chenhui | Li, Jie | Huang, Xinying | Wang, Jie | Chu, Shanshan | Peng, Bin | Cui, Liying | Xu, Qi | Gao, Jing

Article Type: Research Article

Abstract: Background: The established causative mutations in the APP , PSEN1 , and PSEN2 can explain less than 1%,Alzheimer’s disease (AD) patients. Of the identified variants, the PSEN2 mutations are even less common. Objective: With the genetic study from the dementia cohort of Peking Union Medical College Hospital (PUMCH), we aim to illustrate the PSEN2 mutation spectrum and novel functionally validated mutations in Chinese AD patients. Methods: 702 AD participants, aged 30–85, were identified in PUMCH dementia cohort. They all received history inquiry, physical examination, biochemical test, cognitive evaluation, brain CT/MRI, and next-generation DNA …sequencing. Functional analysis was achieved by transfection of the HEK293 cells with plasmids harboring the wild-type PSEN2 or candidate mutations. Results: Nine PSEN2 rare variants were found, including two reported (M239T, R62C) and seven novel variants (N141S, I368F, L396I, G117X, I146T, S147N, H220Y). The HEK293 cells transfected with the PSEN2 N141S, M239T, I368F plasmids showed higher Aβ 42 and Aβ 42 /Aβ 40 levels relative to the wild-type PSEN2 . The PSEN2 L396I, G117X, S147N, H220Y, and R62C did not alter Aβ 42 , Aβ 40 levels, or Aβ 42 /Aβ 40 ratio. 1.9%,(13/702) subjects harbored rare PSEN2 variants. 0.4%,(3/702) subjects carried pathogenic/likely pathogenic PSEN2 mutations. The three subjects with the functionally validated PSEN2 mutations were all familial early-onset AD patients. The common symptoms included amnesia and mental symptom. Additionally, the M239T mutation carrier presented with dressing apraxia, visuospatial agraphia, dyscalculia and visual mislocalization. Conclusion: The PSEN2 N141S, M239T, and I368F are functionally validated mutations. Show more

Keywords: Alzheimer’s disease, pathogenic mutations, PSEN2

DOI: 10.3233/JAD-220194

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

Authors: Orive, Gorka | Lopera, Francisco | Carro, Eva

Article Type: Editorial

DOI: 10.3233/JAD-220144

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-5, 2022

Authors: Castillo-Passi, Rolando I. | Vergara, Rodrigo C. | Rogers, Nicole K. | Ponce, Daniela | Bennett, Magdalena | Behrens, María Isabel

Article Type: Research Article

Abstract: Background: Several epidemiological studies report a negative association between Cancer and Alzheimer’s disease (AD). Objective: To characterize the trajectories of memory loss in individuals with early amnestic cognitive impairment with and without history of previous cancer. Methods: Cognitive deterioration was assessed using the Montreal Cognitive Assessment (MoCA) or MoCA-Memory Index Score (MoCA-MIS) biannually in subjects with early amnestic cognitive impairment followed-up retrospectively from 2007 to 2021. History of Cancer was obtained from clinical records. Simple linear regressions of MoCA-MIS scores were calculated for each subject and analyzed with K-means cluster analysis to identify subgroups with different …cognitive decline trajectories. χ 2 and t tests were used for descriptive categorical and continuous variables and mixed multiple linear regressions to determine cognitive decline covariates. Results: Analysis of the trajectory of cognitive decline in 141 subjects with early amnestic cognitive impairment identified two subgroups: Fast (n  = 60) and Slow (n  = 81) progressors. At baseline Fast progressors had better MoCA-MIS (p  <  0.001) and functionality (CDR p  = 0.02, AD8 p  = 0.05), took less anti-dementia medications (p  = 0.005), and had higher depression rates (p  = 0.02). Interestingly, Fast progressors slowed their speed of memory decline (from 1.6 to 1.1 MoCA-MIS points/year) and global cognitive decline (from 2.0 to 1.4 total MoCA points/year) when Cancer history was present. Conclusion: Two trajectories of amnestic cognitive decline were identified, possibly derived from different neurophysiopathologies or clinical stages. This study suggests that a history of previous Cancer slows down amnestic cognitive decline, specifically in a subgroup of subjects with depression at baseline and accelerated deterioration at follow-up. Show more

Keywords: Alzheimer’s disease, cognitive decline, cognitive dysfunction, memory, mild cognitive impairment

DOI: 10.3233/JAD-215660

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-17, 2022

Authors: LoBue, Christian | Kelley, Brendan J. | Hart, Jr., John | Helphrey, Jessica | Schaffert, Jeff | Cullum, C Munro | Peters, Matthew E. | Douglas, Peter M. | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Short Communication

Abstract: Few studies have examined an association between mild traumatic brain injury (mTBI) and Alzheimer’s disease (AD). For this reason, we compared an AD dementia group with an mTBI history (n  = 10) to a matched AD control group (n  = 20) on measures of cognitive function, cerebral glucose metabolism, and markers of amyloid and tau deposition. Only a trend and medium-to-large effect size for higher phosphorylated and total tau was identified for the mTBI group. A history of mTBI may be associated with greater tau in AD, indicating a potential pathway for increasing risk for AD, though further evaluation with larger samples …is needed. Show more

Keywords: Biomarkers, concussion, dementia, neurodegeneration, risk factor, tau formation, traumatic brain injury

DOI: 10.3233/JAD-220112

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-6, 2022

Authors: Graham, Alicia | Livingston, Gill | Purnell, Lucy | Huntley, Jonathan

Article Type: Systematic Review

Abstract: Background: Traumatic brain injury (TBI) increases the risk of future dementia and Alzheimer’s disease (AD). However, it is unclear whether this is true for mild TBI (mTBI). Objective: To explore the association between mTBI and subsequent risk of developing AD. Method: We systematically searched four electronic databases from January 1954 to April 2020. We included studies reporting primary data and where mTBI preceded AD by≥5 years. We meta-analyzed included studies for both high quality studies and studies with a follow up of > 10 years. Result: We included 5 of the 10,435 results found. Meta-analysis found …a history of mTBI increased risk of AD (pooled relative risk = 1.18, 95% CI 1.11–1.25, N  = 3,149,740). The sensitivity analysis including only studies in which mTBI preceded AD by > 10 years, excluded two very large studies and resulted in wider confidence intervals (RR = 2.02, 95% CI 0.66–6.21, N  = 2307). Conclusion: There is an increased risk of AD following mTBI. Our findings of increased risk even with mTBI means it cannot be assumed that mild head injuries from sports are harmless. The sensitivity analysis suggests that we cannot exclude reverse causation, and longer follow up times are needed. Implementation of policy to reduce mTBIs, including in children and sportsmen, are urgently needed. Further research is needed on the effect of frequency and age at injury of mTBIs. Show more

Keywords: Alzheimer’s disease, meta-analysis, risk factor, systematic review, traumatic brain injury

DOI: 10.3233/JAD-220069

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