Journal of Alzheimer's Disease - Volume 84, issue 4

Authors: Chu, Min | Liu, Li | Wang, Jingjuan | Liu, Lin | Kong, Yu | Jing, Donglai | Xie, Kexin | Cui, Yue | Cui, Bo | Zhang, Jing | Ye, Hong | Li, Junjie | Wang, Lin | Rosa-Neto, Pedro | Gauthier, Serge | Wu, Liyong

Article Type: Research Article

Abstract: Background: The anterior cingulate cortex (ACC) seems to play an important role in behavioral deficits and executive dysfunctions in patients with behavioral variant frontotemporal dementia (bvFTD), while its specific and independent contribution requires clarification. Objective: To identify whether ACC abnormalities in gray matter (GM) volume and standardized uptake value ratio (SUVR) images are associated with disease severity of bvFTD, by analyzing hybrid T1 and 18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG PET). Methods: We enrolled 21 bvFTD patients and 21 healthy controls in the study. Each subject underwent a hybrid PET/MRI study and a standardized neuropsychologic …assessment battery. GM volume and SUVR are voxel-wise calculated and compared. Then we estimate the mean value inside ACC for further partial Pearson’s correlation to explore the association between GM volume/SUVR of the ACC and severity of behavioral deficit as well as executive dysfunction. Results: ACC was shown to be involved in both atrophy and hypometabolism patterns. The partial Pearson’s correlation analysis showed that the SUVR of the ACC was strongly correlated with frontal behavior inventory total score (left r  = –0.85, right r  = –0.85, p  < 0.0001), disinhibition subscale score (left r  = –0.72, p  = 0.002; right = –0.75, p  < 0.0001), and apathy subscale score (left = –0.87, right = –0.85, p  < 0.0001). Conclusion: These findings demonstrated decreased ACC activity contributes to behavioral disturbances of both apathetic and disinhibition syndromes of bvFTD, which can be sensitively detected using 18 F-FDG PET. Show more

Keywords: Anterior cingulate cortex, atrophy, 18F-fluorodeoxyglucose positron emission tomography, frontotemporal dementia, hypometabolism, magnetic resonance imaging

DOI: 10.3233/JAD-215127

Citation: Journal of Alzheimer's Disease, vol. 84, no. 4, pp. 1771-1779, 2021

Authors: Bjorkli, Christiana | Louet, Claire | Flo, Trude Helen | Hemler, Mary | Sandvig, Axel | Sandvig, Ioanna

Article Type: Research Article

Abstract: Background: Preclinical models of Alzheimer’s disease (AD) can provide valuable insights into the onset and progression of the disease, such as changes in concentrations of amyloid-β (Aβ) and tau in cerebrospinal fluid (CSF). However, such models are currently underutilized due to limited advancement in techniques that allow for longitudinal CSF monitoring. Objective: An elegant way to understand the biochemical environment in the diseased brain is intracerebral microdialysis, a method that has until now been limited to short-term observations, or snapshots, of the brain microenvironment. Here we draw upon patient-based findings to characterize CSF biomarkers in a commonly used …preclinical mouse model for AD. Methods: Our modified push-pull microdialysis method was first validated ex vivo with human CSF samples, and then in vivo in an AD mouse model, permitting assessment of dynamic changes of CSF Aβ and tau and allowing for better translational understanding of CSF biomarkers. Results: We demonstrate that CSF biomarker changes in preclinical models capture what is observed in the brain; with a decrease in CSF Aβ observed when plaques are deposited, and an increase in CSF tau once tau pathology is present in the brain parenchyma. We found that a high molecular weight cut-off membrane allowed for simultaneous sampling of Aβ and tau, comparable to CSF collection by lumbar puncture in patients. Conclusion: Our approach can further advance AD and other neurodegenerative research by following evolving neuropathology along the disease cascade via consecutive sampling from the same animal and can additionally be used to administer pharmaceutical compounds and assess their efficacy. Show more

Keywords: Amyloid-β , animal use alternatives, biomarkers, cerebrospinal fluid, neurodegenerative disease, protein aggregation, tau protein

DOI: 10.3233/JAD-210715

Citation: Journal of Alzheimer's Disease, vol. 84, no. 4, pp. 1781-1794, 2021

Authors: Chen, Jen-Hau | Shih, Hua-San | Tu, Jennifer | Chiou, Jeng-Min | Chang, Shu-Hui | Hsu, Wei-Li | Lai, Liang-Chuan | Chen, Ta-Fu | Chen, Yen-Ching

Article Type: Research Article

Abstract: Background: Cognitive frailty integrating impaired cognitive domains and frailty dimensions has not been explored. Objective: This study aimed to explore 1) associations among frailty dimensions and cognitive domains over time and 2) the extended definitions of cognitive frailty for predicting all-cause mortality. Methods: This four-year cohort study recruited 521 older adults at baseline (2011–2013). We utilized 1) generalized linear mixed models exploring associations of frailty dimensions (physical dimension: modified from Fried et al.; psychosocial dimension: integrating self-rated health, mood, and social relationship and support; global frailty: combining physical and psychosocial frailty) with cognition (global and domain-specific) …over time and 2) time-dependent Cox proportional hazard models assessing associations between extended definitions of cognitive frailty (cognitive domains-frailty dimensions) and all-cause mortality. Results: At baseline, the prevalence was 3.0% for physical frailty and 37.6% for psychosocial frailty. Greater physical frailty was associated with poor global cognition (adjusted odds ratio = 1.43–3.29, β: –1.07), logical memory (β: –0.14 to –0.10), and executive function (β: –0.51 to –0.12). Greater psychosocial frailty was associated with poor global cognition (β: –0.44) and attention (β: –0.15 to –0.13). Three newly proposed definitions of cognitive frailty, “mild cognitive impairment (MCI)-psychosocial frailty,” “MCI-global frailty,” and “impaired verbal fluency-global frailty,” outperformed traditional cognitive frailty for predicting all-cause mortality (adjusted hazard ratio = 3.49, 6.83, 3.29 versus 4.87; AIC = 224.3, 221.8, 226.1 versus 228.1). Conclusion: Notably, extended definitions of cognitive frailty proposed by this study better predict all-cause mortality in older adults than the traditional definition of cognitive frailty, highlighting the importance of psychosocial frailty to reduce mortality in older adults. Show more

Keywords: Cognition, cohort study, frailty, mortality

DOI: 10.3233/JAD-215111

Citation: Journal of Alzheimer's Disease, vol. 84, no. 4, pp. 1795-1809, 2021

Authors: Gardener, Hannah | Levin, Bonnie | DeRosa, Janet | Rundek, Tatjana | Wright, Clinton B. | Elkind, Mitchell S.V. | Sacco, Ralph L.

Article Type: Research Article

Abstract: Background: Evidence supports a relationship between loneliness, social isolation, and dementia, but less is known about whether social connections confer protection against cognitive decline in disadvantaged neighborhoods. Objective: This longitudinal population-based study examines the relationship between social connectivity and cognitive impairment in a multi-ethnic cohort with low socioeconomic status and high vascular disease risk. Methods: Northern Manhattan Study participants self-reported frequency of social visits, phone calls, satisfaction with social visits, number of friends, and loneliness at baseline, and were followed prospectively with a series of neuropsychological assessments. Social connectivity was examined in relation to incident mild …cognitive impairment (MCI)/dementia using logistic regression adjusting for demographics and vascular risk factors. Results: Among 952 participants (mean age at first neuropsychological assessment = 69±8 years, 62% women, 17% Black, 13% white, 68% Hispanic), 24% developed MCI/dementia. Participants who had phone contact with friends/family 2 + times/week (91%) had a lower odds of MCI/dementia (OR = 0.52, 95% CI = 0.31–0.89), with no association for frequency of in-person visits. Compared to those who were neither socially isolated (≥3 friends) nor lonely (reference, 73%), those who were socially isolated and lonely (3%) had an increased odds of MCI/dementia (OR = 2.89, 95% CI = 1.19–7.02), but differences were not observed for those who were socially isolated but not lonely (10%, OR = 1.05, 95% CI = 0.60–1.84), nor those who were lonely but not isolated (11%, OR = 1.58, 95% CI = 0.97–2.59). Conclusion: This study raises the possibility that social connections confer some protection for cognitive health in the face of adversity and supports potential opportunities for community social interventions for improving cognition in disadvantaged populations. Show more

Keywords: Dementia, depression, epidemiology, mild cognitive impairment, social isolation

DOI: 10.3233/JAD-210519

Citation: Journal of Alzheimer's Disease, vol. 84, no. 4, pp. 1811-1820, 2021

Authors: Matthiesen, Susan Tomczak | Rosenkjær, Sophie | Pontén, Moa | Jensen, Karin B. | Gottrup, Hanne | Vase, Lene

Article Type: Research Article

Abstract: Background: Non-specific treatment effects, such as expectations, contribute to the effectiveness of pharmacological treatments across diseases. However, the contribution of expectancy, i.e., certainty of receiving treatment, in patients with Alzheimer’s disease (AD) is unknown. Objective: The aim is to investigate whether certainty of receiving a genuine treatment influences the response to active treatment in AD patients. Methods: The efficacy of active treatments in open-label trials, where patients are certain of receiving treatment (100%certainty), was compared to the same active treatments in randomized controlled trials (RCT), where patients are uncertain of receiving treatment or placebo (50%certainty). …Results: In the seven open-label trials, there was no significant difference between post- and pre-treatment scores (difference in means  = 0.14, 95%CI [–0.51; 0.81], p  = 0.66). In the eight RCT trials, there was a significant difference between post- and pre-treatment (difference in means  =  –0.91, 95%CI [–1.43; –0.41], p  < 0.001). There was a statistically significant difference between open-label and RCT trials (difference = 1.06, 95%CI [0.23; 1.90], p  = 0.001). Conclusion: Patients with AD did not benefit from certainty of receiving genuine treatment. This could be due to the nature/progression of the disease, but it could also be related to an order effect in the practice of running AD trials, where RCTs are conducted prior to open label. These findings have implications for the understanding of non-specific treatment effects in AD patients as well as for the design of clinical trials that test pharmacological treatments in AD. Show more

Keywords: Alzheimer’s disease, open-label trials, placebo analgesia, randomized placebo-controlled trials.

DOI: 10.3233/JAD-210108

Citation: Journal of Alzheimer's Disease, vol. 84, no. 4, pp. 1821-1832, 2021

Article Type: Other

DOI: 10.3233/JAD-219011

Citation: Journal of Alzheimer's Disease, vol. 84, no. 4, pp. 1833-1847, 2021

Authors: Almeida-Meza, Pamela | Steptoe, Andrew | Cadar, Dorina

Article Type: Correction

DOI: 10.3233/JAD-219016

Citation: Journal of Alzheimer's Disease, vol. 84, no. 4, pp. 1849-1849, 2021