Journal of Alzheimer's Disease - Volume 97, issue 4

Authors: Groechel, Renee C. | Liu, Albert C. | Koton, Silvia | Kucharska-Newton, Anna M. | Lutsey, Pamela L. | Mosley, Thomas H. | Palta, Priya | Sharrett, A. Richey | Walker, Keenan A. | Wong, Dean F. | Gottesman, Rebecca F.

Article Type: Research Article

Abstract: Background: Psychosocial factors are modifiable risk factors for Alzheimer’s disease (AD). One mechanism linking psychosocial factors to AD risk may be through biological measures of brain amyloid; however, this association has not been widely studied. Objective: To determine if mid-life measures of social support and social isolation in the Atherosclerosis Risk in Communities (ARIC) Study cohort are associated with late life brain amyloid burden, measured using florbetapir positron emission tomography (PET). Methods: Measures of social support and social isolation were assessed in ARIC participants (visit 2: 1990–1992). Brain amyloid was evaluated with florbetapir PET standardized uptake …value ratios (SUVRs; visit 5: 2012–2014). Results: Among 316 participants without dementia, participants with intermediate (odds ratio (OR), 0.47; 95% CI, 0.25–0.88), or low social support (OR, 0.43; 95% CI, 0.22–0.83) in mid-life were less likely to have elevated amyloid SUVRs, relative to participants with high social support. Participants with moderate risk for social isolation in mid-life (OR, 0.32; 95% CI, 0.14–0.74) were less likely to have elevated amyloid burden than participants at low risk for social isolation. These associations were not significantly modified by sex or race. Conclusions: Lower social support and moderate risk of social isolation in mid-life were associated with lower odds of elevated amyloid SUVR in late life, compared to participants with greater mid-life psychosocial measures. Future longitudinal studies evaluating mid-life psychosocial factors, in relation to brain amyloid as well as other health outcomes, will strengthen our understanding of the role of these factors throughout the lifetime. Show more

Keywords: Alzheimer’s disease, amyloid-beta, dementia, mid-life, positron emission tomography, psychosocial factors

DOI: 10.3233/JAD-231218

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1901-1911, 2024

Authors: Li, Da | Sun, Yan | Ding, Lin | Fu, Yan | Zhou, Jie | Yu, Jin-Tai | Tan, Lan

Article Type: Research Article

Abstract: Background: Cerebral microbleeds (CMB) play an important role in neurodegenerative pathology. Objective: The present study aims to test whether cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) level is linked to CMBs in elderly people. Methods: A total of 750 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) who had measurements of GAP-43 and CMBs were included in the study. According to the presence and extent of CMBs, participants were stratified into different groups. Regression analyses were used to assess cross-sectional and longitudinal associations between GAP-43 and CMBs. Results: Participants with CMB were slightly older …and had higher concentrations of CSF GAP43. In multivariable adjusted analyses for age, gender, APOE ɛ 4 status, and cognitive diagnoses, higher CSF GAP-43 concentrations were modestly associated with CMB presence (OR = 1.169, 95% CI = 1.001–1.365) and number (β= 0.020, SE = 0.009, p  = 0.027). Similarly, higher CSF GAP43 concentrations were accrual of CMB lesions, associated with higher CMB progression (OR = 1.231, 95% CI = 1.044–1.448) and number (β= 0.017, SE = 0.005, p  = 0.001) in the follow up scan. In stratified analyses, slightly stronger associations were noted in male participants, those 65 years and older, carriers of APOE ɛ 4 alleles, and with more advanced cognitive disorders. Conclusions: CSF GAP-43 was cross-sectionally associated with the presence and extent of CMBs. GAP-43 might be used as a biomarker to track the dynamic changes of CMBs in elderly persons. Show more

Keywords: Alzheimer’s disease, Alzheimer’s disease Neuroimaging Initiative, cerebral microbleeds, CSF biomarker, GAP-43, synaptic dysfunction

DOI: 10.3233/JAD-230508

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1913-1922, 2024

Authors: Giulietti, Maria Velia | Fabbietti, Paolo | Spatuzzi, Roberta | Vespa, Anna

Article Type: Research Article

Abstract: Background: Many studies have highlighted the effect of training with mindfulness-based interventions (MBIs) on the psycho-physical rebalancing of patients suffering from various pathologies, and their families. Objective: In this study, the effect of a training with mindfulness-based stress reduction (MBSR) on quality of life and emotion regulation (depression) was verified in caregivers (CGs) of patients affected by Alzheimer’s disease at early stage (AD-P). Methods: In this randomized controlled study, 22 CGs (age≥60 years) were treated with MBIs, in particular MBSR, and 22 CGs had no treatment. Tests (T0-T1 six months) included: SF 36-Quality of Life (QoL); …Caregiver Burden Inventory (CBI); FACIT-Spiritual-Well-Being; Beck Depression Inventory (BDI); Everyday Cognition scales; and Mini-Mental State Examination (for AD-P). Results: Significant differences emerged between T0 and T1 for CGs with MBSR in the following dimensions: Depression-BDI (p  > 0.001), Burden CBI-Total (0.001), CBI-Time dependent burden (p  < 0.001), CBI-Developmental burden (p  < 0.001), CBI-Physical burden (p  < 0.001); and pain (p  = 0.002) all decreased; while CBI-Social burden (p  = 0.004), QoL-Health Role Limitation (p  < 0.000), QoL-Role-Limitation-Emotional-Problem (p  < 0.000), QoL-Energy-fatigue (p  < 0.000), QoL-Emotional Well-Being (p  < 0.001), QoL-Social Well Being (p  = 0.010), and QoL-General Health (p  = 0.004) increased. The control group of untreated CG showed a significant worsening in the dimensions of Physical functioning (p  = 0.036) and pain (p  = 0.047). Conclusions: AD-CGs treated with MBI reduced their burden and depression and experienced an improvement in all the dimensions of quality of life. Show more

Keywords: Alzheimer’s disease, burden, caregivers, depression, mindfulness, quality of life

DOI: 10.3233/JAD-230284

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1923-1930, 2024

Authors: Bachand, Annette M. | Dell, Linda D.

Article Type: Research Article

Abstract: Background: Epidemiological studies have reported positive associations between long-term exposure to particulate matter of 2.5 microns or less in diameter (PM2.5 ) and risk of Alzheimer’s disease and other clinical dementia. Many of these studies have analyzed data using Cox Proportional Hazards (PH) regression, which estimates a hazard ratio (HR) for the treatment (in this case, exposure) effect on the time-to-event outcome while adjusting for influential covariates. PM2.5 levels vary over time. As air quality standards for PM2.5 have become more stringent over time, average outdoor PM2.5 levels have decreased substantially. Objective: Investigate whether a Cox …PH analysis that does not properly account for exposure that varies over time could produce a biased HR of similar magnitude to the HRs reported in recent epidemiological studies of PM2.5 and dementia risk. Methods: Simulation analysis. Results: We found that the biased HR can affect statistical analyses that consider exposure levels at event times only, especially if PM2.5 levels decreased consistently over time. Furthermore, the direction of such bias is away from the null and of a magnitude that is consistent with the reported estimates of dementia risk in several epidemiological studies of PM2.5 exposure (HR≈1.2 to 2.0). Conclusions: This bias can be avoided by correctly assigning exposure to study subjects throughout the entire follow-up period. We recommend that investigators provide a detailed description of how time-dependent exposure variables were accounted for in their Cox PH analyses when they report their results. Show more

Keywords: Alzheimer’s disease, ambient air pollution, bias analysis, dementia risk, particulate matter 2.5 microns (PM2.5), survival analysis

DOI: 10.3233/JAD-231046

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1931-1937, 2024

Authors: Kang, Jiseung | Park, Mincheol | Kim, Tae

Article Type: Research Article

Abstract: Background: Vitamin D has neuroprotective and immunomodulating functions that may impact glial cell function in the brain. Previously, we reported molecular and behavioral changes caused by deficiency and supplementation of vitamin D in an Alzheimer’s disease (AD) mouse model. Recent studies have highlighted reactive astrocytes as a new therapeutic target for AD treatment. However, the mechanisms underlying the therapeutic effects of vitamin D on the glial cells of AD remain unclear. Objective: To investigate the potential association between vitamin D deficiency/supplementation and the pathological progression of AD, including amyloid-β (Aβ) pathology and reactive astrogliosis. Methods: Transgenic …hemizygous 5XFAD male mice were subjected to different dietary interventions and intraperitoneal vitamin D injections to examine the effects of vitamin D deficiency and supplementation on AD. Brain tissue was then analyzed using immunohistochemistry for Aβ plaques, microglia, and astrocytes, with quantifications performed via ImageJ software. Results: Our results demonstrated that vitamin D deficiency exacerbated Aβ plaque formation and increased GABA-positive reactive astrocytes in AD model mice, while vitamin D supplementation ameliorated these effects, leading to a reduction in Aβ plaques and GABA-positive astrocytes. Conclusions: Our findings highlight the significant impact of vitamin D status on Aβ pathology and reactive astrogliosis, underscoring its potential role in the prevention and treatment of AD. This study provides the first in vivo evidence of the association between vitamin D and reactive astrogliosis in AD model mice, indicating the potential for targeting vitamin D levels as a novel therapeutic approach for AD. Show more

Keywords: Alzheimer’s disease, amyloid-β, astrocytic GABA, reactive astrocyte, vitamin D, vitamin D deficiency, vitamin D supplementation

DOI: 10.3233/JAD-231033

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1939-1950, 2024

Authors: Matsuoka, Teruyuki | Ismail, Zahinoor | Imai, Ayu | Shibata, Keisuke | Nakamura, Kaeko | Nishimura, Yukihide | Rubinstein, Ellen | Uchida, Hiroyuki | Mimura, Masaru | Narumoto, Jin

Article Type: Research Article

Abstract: Background: Mild behavioral impairment (MBI) and loneliness are associated with cognitive decline and an increased risk of dementia. Objective: Our aim was to examine the validity of the Japanese version of the MBI checklist (MBI-C) and investigate the relationship between loneliness and MBI. Methods: The participants in this cross-sectional study included 5 cognitively normal persons and 75 persons with mild cognitive impairment. MBI-C and the revised University of California at Los Angeles loneliness scale (LS) were used to assess MBI and loneliness, respectively. Diagnostic performance of MBI-C was examined using receiver operating characteristic …analysis. The relationship between MBI-C and LS was examined using multiple linear regression in 67 subjects who were assessed with both scales, with MBI-C total or domain score as the dependent variable and LS as the independent variable, adjusted for age, gender, living situation, presence of visual and hearing impairment, and Mini-Mental State Examination score. Results: Per the Youden index, in this mostly MCI sample, the optimal MBI-C cut-off score was 5.5 with sensitivity 0.917 and specificity 0.949. In multiple linear regression analysis, LS score was detected as a significant predictor of MBI-C total scores, and MBI-C decreased motivation, affective dysregulation, and abnormal thought and perception scores. Conclusions: The caregiver-rated Japanese MBI-C has excellent diagnostic performance. Loneliness is associated with a greater MBI burden, especially in the decreased motivation, affective dysregulation, and abnormal thought and perception domains. Interventions for loneliness in older people may have the potential to improve MBI. Show more

Keywords: Alzheimer’s disease, dementia, living alone, loneliness, mild behavioral impairment, visual impairment

DOI: 10.3233/JAD-230923

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1951-1960, 2024

Authors: Chatzikostopoulos, Thanos | Gialaouzidis, Moses | Koutoupa, Anna | Tsolaki, Magda

Article Type: Research Article

Abstract: Background: In recent years, there has been a growing interest, supported by many experimental and clinical studies, about the benefits of pomegranate in preventing various pathologic conditions, including brain neurodegeneration. The pomegranate seed oil (PSO) contains high levels of fatty acids that have antioxidant and anti-inflammatory properties. Objective: Due to the lack of clinical trials, the aim of the present study was to investigate the effects of PSO on cognition of people with mild cognitive impairment (MCI). Methods: Eighty people with the diagnosis of MCI were randomized forty to take 5 drops of PSO and follow …the Mediterranean Diet (MeDi) and forty just followed MeDi. All were examined with an extensive neuropsychological assessment before and after one year of treatment. Results: The results showed that the participants who took the PSO had statistically significantly better global cognition (p  = 0.004), verbal episodic memory (p  = 0.009), and processing and executive functions (p  < 0.001) in contrast with the participants who did not take it. Conclusions: In conclusion, the PSO can be beneficial for people with MCI as it is helpful for some important cognitive domains. As PSO is a natural product that does not burden the human body, it can be used by people with MCI and be a significant and promising part of holistic approaches for the prevention of dementia. Show more

Keywords: Alzheimer’s disease, mild cognitive impairment, neuropsychological assessment, pomegranate seed oil, prevention, randomized clinical trial

DOI: 10.3233/JAD-231100

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1961-1970, 2024