Journal of Alzheimer's Disease - Volume 91, issue 3

Authors: Cao, Ke | Bay, Allison A. | Hajjar, Ihab | Wharton, Whitney | Goldstein, Felicia | Qiu, Deqiang | Prusin, Todd | McKay, J. Lucas | Perkins, Molly M. | Hackney, Madeleine E.

Article Type: Research Article

Abstract: Background: Functional decline in Alzheimer’s disease (AD) is impacted by impaired ability to integrate and modulate complex cognitive and motor abilities, commonly known as motor-cognitive integration. Impaired motor-cognitive integration occurs in the early stages of AD, prodromal AD (pAD), and may precede other symptoms. Combined motor and cognitive training have been recommended for people with pAD and need to be better researched. Our data suggest that partnered rhythmic rehabilitation (PRR) improves motor-cognitive integration in older adults with cognitive impairment. PRR is an ideal intervention to simultaneously target cardiovascular, social, and motor-cognitive domains important to AD. Objective/Methods: We propose …to conduct a 1-year Phase II, single-blind randomized controlled trial using PRR in 66 patients with pAD. Participants will be assigned to three months of biweekly sessions, followed by nine months of weekly sessions of PRR or group walking (WALK) with 1 : 1 allocation. Group walking in the control group will allow us to compare physical exercise alone versus the added benefit of the cognitively engaging elements of PRR. Results/Conclusion: Using an intent-to-treat approach, this innovative pilot study will 1) Determine acceptability, safety, tolerability, and satisfaction with PRR; 2) Compare efficacy of PRR versus WALK for improving motor-cognitive integration and identify the most sensitive endpoint for a Phase III trial from a set of motor-cognitive, volumetric MRI, and cognitive measures. The study will additionally explore potential neural, vascular, and inflammatory mechanisms by which PRR affects pAD to derive effect size of these intermediary measures and aid us in estimating sample size for a future trial. Show more

Keywords: Dance therapy, exercise, multitasking behavior, neuroprotection

DOI: 10.3233/JAD-220783

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 1019-1033, 2023

Authors: Dai, Wen-Zhuo | Liu, Lu | Zhu, Meng-Zhuo | Lu, Jing | Ni, Jian-Ming | Li, Rong | Ma, Tao | Zhu, Xi-Chen

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is an increasingly common type of dementia. Apolipoprotein E (APOE ) gene is a strong risk factor for AD. Objective: Here, we explored alterations in grey matter structure (GMV) and networks in AD, as well as the effects of the APOE ɛ 4 allele on neuroimaging regions based on structural magnetic resonance imaging (sMRI). Methods: All subjects underwent an sMRI scan. GMV and cortical thickness were calculated using voxel-based morphological analysis, and structural networks were constructed based on graph theory analysis to compare differences between AD and normal controls. …Results: The volumes of grey matter in the bilateral inferior temporal gyrus, right middle temporal gyrus, right inferior parietal lobule, right limbic lobe, right frontal lobe, left anterior cingulate gyrus, and bilateral olfactory cortex of patients with AD were significantly decreased. The cortical thickness in patients with AD was significantly reduced in the left lateral occipital lobe, inferior parietal lobe, orbitofrontal region, precuneus, superior parietal gyrus, right precentral gyrus, middle temporal gyrus, pars opercularis gyrus, insular gyrus, superior marginal gyrus, bilateral fusiform gyrus, and superior frontal gyrus. In terms of local properties, there were significant differences between the AD and control groups in these areas, including the right bank, right temporalis pole, bilateral middle temporal gyrus, right transverse temporal gyrus, left postcentral gyrus, and left parahippocampal gyrus. Conclusion: There were significant differences in the morphological and structural covariate networks between AD patients and healthy controls under APOE ɛ 4 allele effects. Show more

Keywords: Alzheimer’s disease, apolipoprotein E, cortical thickness, grey matter volume, structural covariate network, structural magnetic resonance imaging

DOI: 10.3233/JAD-220877

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 1035-1048, 2023

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. 91, no. 3, pp. 1049-1058, 2023

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 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. 91, no. 3, pp. 1059-1071, 2023

Authors: Eruysal, Emily | Ravdin, Lisa | Zhang, Cenai | Kamel, Hooman | Iadecola, Costantino | Ishii, Makoto

Article Type: Research Article

Abstract: Background: Plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis that is associated with adiposity, has been implicated in Alzheimer’s disease (AD) pathogenesis. However, whether circulating PAI-1 levels are altered during preclinical AD remains unclear. Objective: To measure plasma PAI-1 levels in cognitively normal cerebrospinal fluid (CSF) AD biomarker positive and biomarker negative participants and to examine the association of plasma PAI-1 levels with CSF AD biomarkers and Mini-Mental State Examination (MMSE) scores. Methods: In this cross-sectional study, plasma PAI-1 levels were measured in 155 cognitively normal (Clinical Dementia Rating, CDR 0) non-obese older adults. 29 men …and 26 women were classified as preclinical AD by previously established CSF tau/Aβ42 criteria. All analyses were sex stratified due to reported sex differences in PAI-1 expression. Results: Plasma PAI-1 levels were associated with body mass index (BMI) but not age in men and women. In men, plasma PAI-1 levels and BMI were lower in preclinical AD compared to control. Plasma PAI-1 levels were positively associated with CSF amyloid-β42 (Aβ42) and CSF Aβ42/Aβ40 and negatively associated with CSF tau/Aβ42, while BMI was positively associated with CSF Aβ42 and negatively associated with CSF p-tau181 and CSF tau/Aβ42. In women, plasma PAI-1 levels and BMI were similar between preclinical AD and control and were not associated with CSF AD biomarkers. For men and women, plasma PAI-1 levels and BMI were not associated with MMSE scores. Conclusion: These findings suggest that there are significant sex differences in the systemic metabolic changes seen in the preclinical stage of AD. Show more

Keywords: Adipokines, Alzheimer’s disease, amyloid beta-peptides, body weight, body mass index, biomarker, immunoassay, PAI-1, sexual dimorphism, tau proteins

DOI: 10.3233/JAD-220686

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 1073-1083, 2023

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. 91, no. 3, pp. 1085-1095, 2023

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. 91, no. 3, pp. 1097-1105, 2023

Authors: Posis, Alexander Ivan B. | Yarish, Natalie M. | McEvoy, Linda K. | Jain, Purva | Kroenke, Candyce H. | Saquib, Nazmus | Ikramuddin, Farha | Schnatz, Peter F. | Bellettiere, John | Rapp, Stephen R. | Espeland, Mark A. | Shadyab, Aladdin H.

Article Type: Research Article

Abstract: Background: Social support may be a modifiable risk factor for cognitive impairment. However, few long-term, large prospective studies have examined associations of various forms of social support with incident mild cognitive impairment (MCI) and dementia. Objective: To examine associations of perceived social support with incident MCI and dementia among community-dwelling older women. Methods: This prospective cohort study included 6,670 women from the Women’s Health Initiative Memory Study who were cognitively unimpaired at enrollment. We used Cox proportional hazards models to assess associations between perceived social support with incident MCI, dementia, or either MCI/dementia during an average …10.7 (SD = 6.1)-year follow-up. Modelling was repeated for emotional/information support, affection support, tangible support, and positive social interaction subscales of social support. Results: Among 6,670 women (average age = 70 years [SD = 3.8]; 97.0% non-Hispanic/Latina; 89.8% White), greater perceived social support was associated with lower risk of MCI/dementia after adjustment for age, ethnicity, race, hormone therapy, education, income, diabetes, hypertension, and body mass index (Tertile [T]3 versus T1: HR = 0.85, 95% CI 0.74–0.99; p trend  = 0.08). Associations were significant for emotional/information support (T3 versus T1: HR = 0.84, 95% CI 0.72–0.97; p trend  = 0.04) and positive social interaction (T3 versus T1: HR = 0.85, 95% CI 0.73–0.99; p trend  = 0.06) subscales. Associations were attenuated and not significant after adjustment for depressive symptom severity. Objective: Perceived social support, emotional/information support, and positive social interaction were associated with incident MCI/dementia among older women. Results were not significant after adjustment for depressive symptom severity. Improving social support may reduce risk of MCI and dementia in older women. Show more

Keywords: Cognitive aging, epidemiology, psychosocial, women’s health

DOI: 10.3233/JAD-220967

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 1107-1119, 2023

Authors: Liu, Jia-Yao | Ma, Ling-Zhi | Wang, Jun | Cui, Xin-Jing | Sheng, Ze-Hu | Fu, Yan | Li, Meng | Ou, Ya-Nan | Yu, Jin-Tai | Tan, Lan | Lian, Yan

Article Type: Research Article

Abstract: Background: APOE ɛ4 genotype was correlated with exacerbation of pathology and higher risk of dementia in Parkinson’s disease (PD). Meanwhile, the differential influence of APOE ɛ4 on cognition in young and old individuals interpreted as antagonistic pleiotropy. Objective: To examine whether the effect of APOE ɛ4 on cognitive progression in de novo PD is age dependent. Methods: In this study, 613 de novo PD patients were recruited from Parkinson’s Progression Markers Initiative (PPMI). To examine the age-dependent relationship between APOE ɛ4 and cognitive changes, we added 3-way interaction of APOE …ɛ4*baseline age*time to the linear mixed-effect (LME) models and evaluated the specific roles of APOE ɛ4 in the middle age group and elderly group separately. Cox regression was utilized to examine the progression of cognition in age-stratified PD participants. Results: Age significantly modified relationship between APOE ɛ4 and cognitive changes in most cognitive domains (pinteraction <0.05). In the elderly group, APOE ɛ4 carriers showed steeper decline in global cognition (p  = 0.001) as well as in most cognitive domains, and they had a greater risk of cognitive progression (adjusted HR 1.625, 95% CI 1.143–2.310, p  = 0.007), compared with non-carriers. However, in the middle age group, no significant relationships between APOE ɛ4 and cognitive decline can be detected. Conclusion: Our results indicated that the APOE ɛ4 allele has an age-dependent effect on cognitive decline in PD patients. The underlying mechanisms need to be investigated in the future. Show more

Keywords: Age, APOE ɛ4, cognition, Parkinson’s disease

DOI: 10.3233/JAD-220976

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 1121-1132, 2023

Authors: Leng, Yue | Stone, Katie L. | Yaffe, Kristine

Article Type: Research Article

Abstract: Background: The effect of sleep medications on cognition in older adults is controversial, possibly dependent upon sleep quality, and may differ by race. Objective: To determine the longitudinal association between sleep medication use and incident dementia over 15 years, and to explore whether the association is independent of nighttime sleep disturbances and if it differs by race. Methods: We examined 3,068 community-dwelling older adults (aged 74.1±2.9 years, 41.7% Black, 51.5% female) without dementia. Sleep medication use was recorded three times by asking “Do you take sleeping pills or other medications to help you sleep?” with the …response options: “Never (0)”, “Rarely (≤1/month)”, “Sometimes (2–4/month)”, “Often (5–15/month)”, or “Almost Always (16–30/month)”. Incident dementia was defined using hospitalization records, dementia medication prescription or clinically significant decline in global cognition. Results: 138 (7.71%) of Whites and 34 (2.66%) of Blacks reported taking sleep medications “often or almost always”. Whites were almost twice as likely to take all prescription hypnotics. 617 participants developed dementia over the follow-up. After adjustment for all covariates, participants who reported taking sleep medications ≥ 5/month versus ≤1/month were significantly more likely to develop dementia, and the association was only observed among Whites (HR = 1.79,1.21–2.66) but not Blacks (HR = 0.84,0.38–1.83); p for interaction = 0.048. Further adjustment for nighttime sleep did not appreciably alter the results. The association was similar for the cumulative frequency of sleep medication use and remained after introducing a time lag of 3 years. Conclusion: Frequent sleep medication use was associated with an increased risk of dementia in White older adults. Further research is needed to determine underlying mechanisms. Show more

Keywords: Dementia, epidemiology, medication, race, sleep

DOI: 10.3233/JAD-221006

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 1133-1139, 2023