Journal of Alzheimer's Disease - Volume 82, issue 4

Authors: Borg, Céline | Rouch, Isabelle | Pongan, Elodie | Getenet, Jean Claude | Bachelet, Romain | Herrmann, Mathieu | Bohec, Anne-Lise | Laurent, Bernard | COVCARE Group | Rey, Romain | Dorey, Jean-Michel

Article Type: Research Article

Abstract: Background: People with dementia (PWD) and their caregivers are populations highly vulnerable to COVID-19 pandemic and its consequences. A better knowledge of the living conditions during the first lockdown is necessary to prevent the risk of poor mental health (PMH) in this population. Objective: The present study aimed to compare the mental health of caregivers of PWD living at home or in nursing-homes and to identify specific factors influencing their mental health. Methods: We conducted an anonymous cross-sectional online survey in France from March 17 to May 11, 2020. Three hundred and eighty-nine caregivers accompanying a …PWD living at home (HC) and 159 accompanying a PWD living in a nursing home (NHC) participated in the study. Caregivers’ mental health including anxiety, depression, stress, and burden was assessed with self-reported standardized scales. Results: Half of the caregivers exhibited PMH, including depression, anxiety, or self-reported stress. Similar PMH rates were provided whatever the PWD place of residence. Regarding HC, our results also highlighted a number of risk factors for PMH, including the fact that caregiver live with PWD, to give increased support to PWD, and to feel more isolated for managing PWD since lockdown. Conclusion: PMH was observed for caregivers of PWD during lockdown, whatever PWD living place, suggesting that concern for PWD may explain more of caregiver distress than increased material tasks. In the future, it will be necessary to pay attention to caregivers after the crisis by estimating the longer-term impact on their mental health. Show more

Keywords: Alzheimer’s disease, caregivers, COVID-19, dementia, lockdown, mental health

DOI: 10.3233/JAD-210079

Citation: Journal of Alzheimer's Disease, vol. 82, no. 4, pp. 1531-1541, 2021

Authors: Chao, Linda L. | Lee, Jennifer A. | Martinez, Steven | Barlow, Cody | Chesney, Margaret A. | Mehling, Wolf E. | Barnes, Deborah E.

Article Type: Research Article

Abstract: Background: Preventing Loss of Independence through Exercise (PLIÉ) is a group movement program initially developed for people with mild-to-moderate dementia that integrates principles from several well-established traditions to specifically address the needs of people with cognitive impairment. Objective: To investigate whether PLIÉ would benefit cognitive and behavioral outcomes and functional brain connectivity in older adults with milder forms of cognitive impairment. Methods: Participants (≥55 y) with subjective memory decline (SMD) or mild cognitive impairment (MCI) were assessed with tests of cognitive and physical function, self-report questionnaires, and resting state functional magnetic resonance imaging (rs-fMRI) on a …3 Tesla scanner before and after participating in twice weekly PLIÉ classes for 12 weeks at the San Francisco Veterans Affairs Medical Center. Results: Eighteen participants completed the pre-post intervention pilot trial. We observed significant improvements on the Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-cog; effect size 0.34, p  = 0.002) and enhanced functional connections between the medial prefrontal cortex (mPFC) and other nodes of the default mode network (DMN) after PLIÉ. Improvements (i.e., lower scores) on ADAS-cog were significantly correlated with enhanced functional connectivity between the mPFC and left lateral parietal cortex (Spearman’s ρ = –0.74, p  = 0.001) and between the mPFC and right hippocampus (Spearman’s ρ = –0.83, p  = 0.001). After completing PLIÉ, participants reported significant reductions in feelings of social isolation and improvements in well-being and interoceptive self-regulation. Conclusion: These preliminary findings of post-PLIÉ improvements in DMN functional connectivity, cognition, interoceptive self-regulation, well-being and reduced feelings of social isolation warrant larger randomized, controlled trials of PLIÉ in older adults with SMD and MCI. Show more

Keywords: Aging, cognitive dysfunction, exercise therapy, memory disorders, mild cognitive impairment, mind-body therapies, self-report

DOI: 10.3233/JAD-210159

Citation: Journal of Alzheimer's Disease, vol. 82, no. 4, pp. 1543-1557, 2021

Authors: Shang, Xianwen | Hodge, Allison M. | Hill, Edward | Zhu, Zhuoting | He, Mingguang

Article Type: Research Article

Abstract: Background: A few studies have linked dietary patterns and sleep to cognitive decline. Objective: To examine the independent and joint associations of dietary patterns and sleep with cognitive decline. Methods: Our analysis included 2,307 participants aged 55– 89 years at baseline from the China Health and Nutrition Survey. Dietary intake was assessed using weighing methods in combination with 24 h dietary recalls for three consecutive days. Exploratory factor analysis was applied to identify major dietary factors. Cognition was assessed in 1997, 2000, 2004, 2006, and 2015. Results: Five dietary patterns were identified: dairy-fruits-fast foods, grains-vegetables-pork, …plant-based food, beans-mushroom, and beverages-nuts patterns. Beans-mushroom pattern and sleep duration of 8 h/day were defined as healthy habits. There was a positive association between the beans-mushroom pattern and change in the global cognitive Z-score over seven years (β (95% CI) for quintile 5 versus quintile 1:0.17 (0.05, 0.30)). Compared to individuals with sleep duration of 8 h/day, those with sleep duration of≤5 h/day (β (95% CI): – 0.23 (– 0.45, – 0.00)) or > 10 h/day (– 0.52 (– 0.73, – 0.32)) had a greater decrease in global cognitive Z-score. Compared to individuals with no healthy patterns, those with a healthy dietary pattern only (β (95% CI): 0.18 (0.08, 0.28)), healthy sleep pattern only (0.13 (0.04, 0.23), and both healthy dietary and sleep patterns (0.19 (0.08, 0.31)) had a relative increase in global cognitive Z-score. Conclusion: Our findings highlight the importance of involving both diet and sleep as intervention priorities for the potential prevention of cognitive decline. Show more

Keywords: Cognitive decline, dietary pattern, sleep duration

DOI: 10.3233/JAD-201329

Citation: Journal of Alzheimer's Disease, vol. 82, no. 4, pp. 1559-1571, 2021

Authors: Franks, Katherine H. | Bransby, Lisa | Saling, Michael M. | Pase, Matthew P.

Article Type: Research Article

Abstract: Background: Although many studies have investigated the association between stress and risk of dementia, findings are inconsistent due to the variation in the measures used to assess stress. Objective: We conducted a systematic review and meta-analysis to investigate the association between psychological stress (including neuroticism, stressful life events, and perceived stress) and the risk of incident dementia and mild cognitive impairment in adults. Methods: PsycINFO, Embase, and MEDLINE were searched to October 2020 for eligible observational, prospective studies. Of the 1,607 studies screened, 26 (24 unique cohorts) were included in the qualitative analysis and 16 (15 …unique cohorts) were included in the quantitative analysis. Results: Across studies, higher perceived stress was significantly associated with an increased risk of mild cognitive impairment (Cases/Total N  = 207/860: hazard ratio [HR] = 1.19, 95% confidence interval [CI] = 1.03–1.38) and all-cause dementia (Cases/Total N  = 203/1,882: HR = 1.44, 95% CI = 1.07–1.95). Exposure to two or more stressful life events (versus none) was significantly associated with an increased risk of all-cause dementia (Cases/Total N  = 3,354/11,597: HR = 1.72, 95% CI = 1.14–2.60), while one or more stressful life events was not. Higher neuroticism was significantly associated with an increased risk of Alzheimer’s disease dementia (Cases/Total N  = 497/4,771: HR = 1.07, 95% CI = 1.01–1.12), but not all-cause dementia. Conclusion: This review suggests that psychological stress in adulthood is associated with an increased risk of dementia. Further research is needed to clarify the mechanisms underlying these associations. Show more

Keywords: Dementia, meta-analysis, mild cognitive impairment, neuroticism, psychological stress

DOI: 10.3233/JAD-210094

Citation: Journal of Alzheimer's Disease, vol. 82, no. 4, pp. 1573-1590, 2021

Authors: Park, Jaehong | Kim, Tae Jun | Song, Joo Hye | Jang, Hyemin | Kim, Ji Sun | Kang, Sung Hoon | Kim, Hang-Rai | Hwangbo, Song | Shin, Hee Young | Na, Duk L. | Seo, Sang Won | Kim, Hee Jin | Kim, Jae J.

Article Type: Research Article

Abstract: Background: An association between Helicobacter pylori (H. pylori ) infection and dementia was reported in previous studies; however, the evidence is inconsistent. Objective: In the present study, the association between H. pylori infection and brain cortical thickness as a biomarker of neurodegeneration was investigated. Methods: A cross-sectional study of 822 men who underwent a medical health check-up, including an esophagogastroduodenoscopy and 3.0 T magnetic resonance imaging, was performed. H. pylori infection status was assessed based on histology. Multiple linear regression analyses were conducted to evaluate the relationship between H. pylori infection and …brain cortical thickness. Results: Men with H. pylori infection exhibited overall brain cortical thinning (p  = 0.022), especially in the parietal (p  = 0.008) and occipital lobes (p  = 0.050) compared with non-infected men after adjusting for age, educational level, alcohol intake, smoking status, and intracranial volume. 3-dimentional topographical analysis showed that H. pylori infected men had cortical thinning in the bilateral lateral temporal, lateral frontal, and right occipital areas compared with non-infected men with the same adjustments (false discovery rate corrected, Q  < 0.050). The association remained significant after further adjusting for inflammatory marker (C-reactive protein) and metabolic factors (obesity, dyslipidemia, fasting glucose, and blood pressure). Conclusion: Our results indicate H. pylori infection is associated with neurodegenerative changes in cognitive normal men. H. pylori infection may play a pathophysiologic role in the neurodegeneration and further studies are needed to validate this association. Show more

Keywords: Cognitive impairment, dementia, H. pylori, neurodegeneration

DOI: 10.3233/JAD-210119

Citation: Journal of Alzheimer's Disease, vol. 82, no. 4, pp. 1591-1599, 2021

Authors: Fuglsang, Cecilia H. | Nagy, David | Troelsen, Frederikke S. | Farkas, Dora K. | Henderson, Victor W. | Sørensen, Henrik T.

Article Type: Research Article

Abstract: Background: Venous thromboembolism (VTE) may be the first manifestation of occult cancer. Dementia has been linked to reduced cancer risk. Objective: We examined the risk of cancer following VTE in people with dementia in comparison to the risk in the general population. Methods: We conducted a population-based Danish registry-based cohort study following patients with a first-time VTE and a previous or concurrent diagnosis of dementia during the period 1 April 1996 –31 December 2017. We followed the study participants from date of VTE until diagnosis of cancer, death, emigration, or end of study period, whichever came …first. The absolute risk of cancer within one year after VTE was computed, treating death as a competing risk. We calculated gender, age, and calendar-period standardized incidence ratios (SIRs) of cancer based on national cancer rates. Results: We followed 3,552 people with dementia and VTE for a median of 1.3 years. Within the first year after VTE, they had a 90% increased risk of cancer in comparison with the general population [SIR: 1.9 (95% confidence interval: 1.6–2.4)]. During subsequent follow-up years, the SIR fell to 0.7 (95% confidence interval: 0.5–0.8). Findings for Alzheimer’s disease and VTE were similar. Conclusion: People with dementia have an increased risk of a cancer diagnosis during the first year following VTE, perhaps related to increased surveillance, and a lower risk thereafter. Overall risk is similar to that of the general population. Show more

Keywords: Alzheimer’s disease, cohort study, dementia, epidemiology, neoplasms, venous thromboembolism

DOI: 10.3233/JAD-201530

Citation: Journal of Alzheimer's Disease, vol. 82, no. 4, pp. 1601-1608, 2021

Authors: Taudorf, Lærke | Nørgaard, Ane | Islamoska, Sabrina | Laursen, Thomas Munk | Waldemar, Gunhild

Article Type: Research Article

Abstract: Background: Dementia is associated with increased mortality. However, it is not clear whether causes of death in people with dementia have changed over time. Objective: To investigate if causes of death changed over time in people with dementia compared to the general elderly population. Methods: We included longitudinal data from nationwide registries on all Danish residents aged≥65 years to 110 years who died between 2002 to 2015. We assessed the annual frequency of dementia-related deaths (defined as a dementia diagnosis registered as a cause of death) and of underlying causes of death in people registered with …dementia compared to the general elderly population. Results: From 2002 to 2015, 621,826 people died, of whom 103,785 were diagnosed with dementia. During this period, the percentage of dementia-related deaths increased from 10.1% to 15.2% in women, and from 6.3% to 9.5% in men in the general elderly population. From 2002 to 2015, dementia became the leading, registered underlying cause of death in people diagnosed with dementia. Simultaneously, a marked decline in cardiovascular and cerebrovascular deaths was observed in people with and without dementia. Conclusion: This is the first study to investigate if the causes of death change over time in people diagnosed with dementia compared with the general elderly population. The increase in the registration of dementia as an underlying cause of death could reflect increasing awareness that dementia is fatal. Show more

Keywords: Cause of death, death certificates, dementia, registries

DOI: 10.3233/JAD-201400

Citation: Journal of Alzheimer's Disease, vol. 82, no. 4, pp. 1609-1618, 2021

Authors: Mancini, Gianni | Dias, Candida | Lourenço, Catia F. | Laranjinha, Joao | de Bem, Andreza | Ledo, Ana

Article Type: Research Article

Abstract: Background: Ample evidence from clinical and pre-clinical studies suggests mid-life hypercholesterolemia as a risk factor for developing Alzheimer’s disease (AD) at a later age. Hypercholesterolemia induced by dietary habits can lead to vascular perturbations that increase the risk of developing sporadic AD. Objective: To investigate the effects of a high fat/cholesterol diet (HFCD) as a risk factor for AD by using a rodent model of AD and its correspondent control (healthy animals). Methods: We compared the effect of a HFCD in normal mice (non-transgenic mice, NTg) and the triple transgenic mouse model of AD (3xTgAD). We …evaluated cognitive performance in relation to changes in oxidative metabolism and neuron-derived nitric oxide (• NO) concentration dynamics in hippocampal slices as well as histochemical staining of markers of the neurovascular unit. Results: In NTg, the HFCD produced only moderate hypercholesterolemia but significant decline in spatial memory was observed. A tendency for decrease in • NO production was accompanied by compromised mitochondrial function with decrease in spare respiratory capacity. In 3xTgAD mice, a robust increase in plasma cholesterol levels with the HFCD did not worsen cognitive performance but did induce compromise of mitochondrial function and significantly decreased • NO production. We found increased staining of biomarkers for astrocyte endfeet and endothelial cells in 3xTgAD hippocampi, which was further increased by the HFCD. Conclusion: A short term (8 weeks) intervention with HFCD can produce an AD-like phenotype even in the absence of overt systemic hypercholesterolemia and highlights mitochondrial dysfunction as a link between hypercholesterolemia and sporadic AD. Show more

Keywords: Alzheimer’s disease, high fat/cholesterol diet, hippocampus, spare respiratory capacity

DOI: 10.3233/JAD-210122

Citation: Journal of Alzheimer's Disease, vol. 82, no. 4, pp. 1619-1633, 2021

Authors: Wang, Wen-Zhi | Li, Ming-Wei | Chen, Ying | Liu, Li-Yuan | Xu, Yong | Xia, Zeng-Hui | Yu, Yang | Wang, Xiao-Dan | Chen, Wei | Zhang, Feng | Xu, Xiao-Yan | Gao, Yong-Feng | Zhang, Ji-Guo | Qin, Shu-Cun | Wang, Hao

Article Type: Research Article

Abstract: Background: Phospholipid transfer protein (PLTP) belongs to the lipid transfer glycoprotein family. Studies have shown that it is closely related to Alzheimer’s disease (AD); however, the exact effect and mechanism remain unknown. Objective: To observe the effect of PLTP overexpression on behavioral dysfunction and the related mechanisms in APP/PS1/Tau triple transgenic (3×Tg-AD) mice. Methods: AAV-PLTP-EGFP was injected into the lateral ventricle to induce PLTP overexpression. The memory of 3×Tg-AD mice and wild type (WT) mice aged 10 months were assessed using Morris water maze (MWM) and shuttle-box passive avoidance test (PAT). Western blotting and ELISA assays …were used to quantify the protein contents. Hematoxylin and eosin, Nissl, and immunochemistry staining were utilized in observing the pathological changes in the brain. Results: 3×Tg-AD mice displayed cognitive impairment in WMW and PAT, which was ameliorated by PLTP overexpression. The histopathological hallmarks of AD, senile plaques and neurofibrillary tangles, were observed in 3×Tg-AD mice and were improved by PLTP overexpression. Besides, the increase of amyloid-β42 (Aβ42 ) and Aβ40 were found in the cerebral cortex and hippocampus of 3×Tg-AD mice and reversed by PLTP overexpression through inhibiting APP and PS1. PLTP overexpression also reversed tau phosphorylation at the Ser404, Thr231 and Ser199 of the hippocampus in 3×Tg-AD mice. Furthermore, PLTP overexpression induced the glycogen synthase kinase 3β (GSK3β) inactivation via upregulating GSK3β (pSer9). Conclusion: These results suggest that PLTP overexpression has neuroprotective effects. These effects are possibly achieved through the inhibition of the Aβ production and tau phosphorylation, which is related to GSK3β inactivation. Show more

Keywords: Alzheimer’s disease, 3×Tg AD mice, GSK3β , PLTP

DOI: 10.3233/JAD-210463

Citation: Journal of Alzheimer's Disease, vol. 82, no. 4, pp. 1635-1649, 2021

Authors: Gabriel, Anna | Lehner, Carolin T. | Höhler, Chiara | Schneider, Thomas | Pfeiffer, Tessa P.T. | Diehl-Schmid, Janine | Hermsdörfer, Joachim

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) affects several cognitive functions and causes altered motor function. Fine motor deficits during object manipulation are evident in other neurological conditions, but have not been assessed in dementia patients yet. Objective: Investigate reactive and anticipatory grip force control in response to unexpected and expected load force perturbation in AD. Methods: Reactive and anticipatory grip force was investigated using a grip-device with force sensors. In this pilot study, fifteen AD patients and fourteen healthy controls performed a catching task. They held the device with one hand while a sandbag was dropped into an …attached receptacle either by the experimenter or by the participant. Results: In contrast to studies of other neurological conditions, the majority of AD patients exerted lower static grip force levels than controls. Interestingly, patients who were slow in the Luria’s three-step test produced normal grip forces. The timing and magnitude of reactive grip force control were largely preserved in patients. In contrast, timing and extent of anticipatory grip forces were impaired in patients, although anticipatory control was generally preserved. These deficits were correlated with decreasing Mini-Mental State Examination scores. Apraxia scores, assessed by pantomime of tool-use, did not correlate with performance in the catching task. Conclusion: We interpreted the decreased grip force in AD in the context of loss of strength and lethargy, typical for patients with AD. The lower static grip force during object manipulation may emerge as a potential biomarker for early stages of AD, but more studies with larger sample sizes are necessary. Show more

Keywords: Alzheimer’s disease, dementia, early diagnosis, fine motor control, hand strength

DOI: 10.3233/JAD-210387

Citation: Journal of Alzheimer's Disease, vol. 82, no. 4, pp. 1651-1665, 2021