Journal of Alzheimer's Disease - Volume 74, issue 2

Authors: Miguel, Laetitia | Frebourg, Thierry | Campion, Dominique | Lecourtois, Magalie

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is neuropathologically defined by two key hallmarks: extracellular senile plaques composed primarily of amyloid-β (Aβ) peptide and intraneuronal neurofibrillary tangles, containing abnormally hyperphosphorylated tau protein. The tau protein is encoded by the MAPT gene. Recently, the H1 and H2 haplotypes of the MAPT gene were associated with AD risk. The minor MAPT H2 haplotype has been linked with a decreased risk of developing late-onset AD (LOAD). MAPT haplotypes show different levels of MAPT/Tau expression with H1 being ∼1.5-fold more expressed than H2, suggesting that MAPT expression level could be related to …LOAD risk. In this study, we investigated whether this moderate difference in MAPT/Tau expression could influence Aβ-induced toxicity in vivo. We show that modest overexpression of tau protein in Drosophila exacerbates neuronal phenotypes in AβPP/BACE1 flies. The exacerbation of neuronal defects correlates with the accumulation of insoluble dTau oligomers, suggesting that the moderate difference in level of tau expression observed between H1 and H2 haplotypes could influence Aβ toxicity through the production of oligomeric tau insoluble species. Show more

Keywords: Alzheimer’s disease, amyloid-β peptide, Drosophila , oligomers, tau

DOI: 10.3233/JAD-190906

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 637-647, 2020

Authors: Livny, Abigail | Schnaider Beeri, Michal | Heymann, Anthony | Moshier, Erin | Berman, Yuval | Mamistalov, Mary | Shahar, Danit-Rivka | Tsarfaty, Galia | Leroith, Derek | Preiss, Rachel | Soleimani, Laili | Silverman, Jeremy M. | Bendlin, Barbara B. | Levy, Andrew | Ravona-Springer, Ramit

Article Type: Research Article

Abstract: Backgrounds: The efficacy of vitamin E in prevention of diabetes-related complications differs by Haptoglobin (Hp) genotype. Objective: To examine the role of Hp genotype in the relationship of vitamin E intake with brain volume in cognitively normal elderly patients with type 2 diabetes. Methods: Brain volumes for the superior, middle, and inferior frontal gyri and for the middle temporal gyrus were generated from structural T1 MRI in 181 study participants (Hp 1-1: n  = 24, Hp 2-1: n  = 77, Hp 2-2: n  = 80). Daily vitamin E intake was assessed using the Food Frequency Questionnaire. Analyses of covariance, …controlling for demographic and cardiovascular variables was used to evaluate whether the association of daily vitamin E intake with brain volume was modified by Hp genotype. Results: Average age was 70.8 (SD = 4.2) with 40% females, and mean Mini-Mental State Examination score of 28.17 (SD = 1.90). A significant interaction was found between vitamin E intake and Hp genotype in inferior frontal gyrus’ volume; p  = 0.0108. For every 1 microgram increase in vitamin E intake, the volume of the inferior frontal gyrus decreased by 0.955% for Hp 1-1 (p  = 0.0348), increased by 0.429% for Hp 2-1 (p  = 0.0457), and by 0.077% for Hp 2-2 (p  = 0.6318). There were no significant interactions between vitamin E intake and Hp genotype for the middle (p  = 0.6011) and superior (p  = 0.2025) frontal gyri or for the middle temporal gyrus (p  = 0.503). Conclusions: The effect of dietary vitamin E on the brain may differ by Hp genotype. Studies examining the impact of vitamin E on brain-related outcomes should consider Hp genotype. Show more

Keywords: Brain volume, diabetes, haptoglobin genotype, vitamin E

DOI: 10.3233/JAD-191294

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 649-658, 2020

Authors: Moazzami, Kasra | Wittbrodt, Matthew T. | Lima, Bruno B. | Kim, Jeong Hwan | Hammadah, Muhammad | Ko, Yi-An | Obideen, Malik | Abdelhadi, Naser | Kaseer, Belal | Gafeer, M. Mazen | Nye, Jonathon A. | Shah, Amit J. | Ward, Laura | Raggi, Paolo | Waller, Edmund K. | Bremner, J. Douglas | Quyyumi, Arshed A. | Vaccarino, Viola

Article Type: Research Article

Abstract: Background: Circulating progenitor cells (CPC) have been associated with memory function and cognitive impairment in healthy adults. However, it is unclear whether such associations also exist in patients with coronary artery disease (CAD). Objective: To assess the association between CPCs and memory performance among individuals with CAD. Methods: We assessed cognitive function in 509 patients with CAD using the verbal and visual Memory subtests of the Wechsler memory scale-IV and the Trail Making Test parts A and B. CPCs were enumerated with flow cytometry as CD45med /CD34+ blood mononuclear cells, those co-expressing other epitopes representing populations …enriched for hematopoietic and endothelial progenitors. Results: After adjusting for demographic and cardiovascular risk factors, lower number of endothelial progenitor cell counts were independently associated with lower visual and verbal memory scores (p for all < 0.05). There was a significant interaction in the magnitude of this association with race (p  < 0.01), such that the association of verbal memory scores with endothelial progenitor subsets was present in Black but not in non-Black participants. No associations were present with the hematopoietic progenitor-enriched cells or with the Trail Making Tests. Conclusion: Lower numbers of circulating endothelial progenitor cells are associated with cognitive impairment in patients with CAD, suggesting a protective effect of repair/regeneration processes in the maintenance of cognitive status. Impairment of verbal memory function was more strongly associated with lower CPC counts in Black compared to non-Black participants with CAD. Whether strategies designed to improve regenerative capacity will improve cognition needs further study. Show more

Keywords: Circulating progenitor cells, cognitive impairment, coronary artery disease, dementia, memory, trail making tests, Wechsler Memory Scale

DOI: 10.3233/JAD-191063

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 659-668, 2020

Authors: Zeghari, Radia | Manera, Valeria | Fabre, Roxane | Guerchouche, Rachid | König, Alexandra | Phan Tran, Minh Khue | Robert, Philippe

Article Type: Research Article

Abstract: Background: Apathy, a highly prevalent behavioral disorder in Alzheimer’s disease and other related disorders, is currently assessed using clinical scales as it is for all neuropsychiatric disorders. Objective: The aim of this study is to propose a new type of assessment using new technologies designed to assess loss of interest by a more implicit and indirect method. Methods: The Interest Game is a form of interactive self-report, where categories of interests are presented in order to quantify them and identify the activities that constitute them. Two indices can be extracted, the number of categories and the …number of activities selected. We compared the scores between three groups: Apathetic (A) and Non-Apathetic (NA) subjects (according to the Apathy Diagnostic Criteria) and controls with no objective cognitive impairment. Results: 95 subjects were included. Results showed that subjects from the A group had significantly less interests (both categories and images selected) than the NA group. As expected, the control group selected a higher number of categories than the other groups. The diagnosis (minor or major neurocognitive disorder) and level of education had also a significant effect on the number of categories selected. Furthermore, subjects with major neurocognitive disorder (NCD) had significantly less interests than minor NCD group. The number of categories measure was more sensitive than the number of images selected. Conclusion: The Interest Game is a promising tool to quantify and identify subject interests and differentiate between apathetic and non-apathetic subjects. Future studies should focus on including more apathetic subjects in the minor NCD group and validating this tool with the general population. Show more

Keywords: Apathy, interest, leisure activities, neurocognitive disorders, serious games

DOI: 10.3233/JAD-191282

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 669-677, 2020

Authors: Zhu, Yi | Zhong, Qian | Ji, Jie | Ma, Jinhui | Wu, Han | Gao, Yaxin | Ali, Nawab | Wang, Tong

Article Type: Research Article

Abstract: Background: Regular aerobic exercises could improve global cognition in older adults with mild cognitive impairment (MCI), such as aerobic dance a type of commonly practiced aerobic exercises. However, its effects remain debatable in improving the cognitive function in patients with MCI. Objective: The aim of this systematic review and meta-analysis is to evaluate the effects of aerobic dance on cognitive function among older adults with MCI. Methods: We searched articles in the MEDLINE, PubMed, Embase, and The Cochrane Library databases from inception to 28 February 2019, with the following criteria: 1) randomized controlled trials; 2) older …adults with MCI; 3) aerobic dance intervention. Results: Five studies of 842 participants were identified. This meta-analysis showed that aerobic dance can significantly improve global cognition (Mini-Mental State Examination: MD = 1.43; 95% CI:[0.59, 2.27]; p  = 0.0009; Alzheimer’s Disease Assessment Scale-Cognitive Subscale: MD=–2.30; 95% CI:[–3.60, –1.00]; p  = 0.0005), and delayed recall ability (SMD = 0.46;95% CI: [0.30, 0.62]; p  < 0.00001) in older adults with MCI. In addition, have positive effects on improving executive function (Trial-Making Test A: MD = –2.37;95% CI:[–4.16, –0.58]; p  = 0.010; Trial-Making Test B: MD = –16.0; 95% CI: [–30.03, –2.11]; p  = 0.020) and immediate recall ability (SMD = 0.24;95% CI: [0.01, 0.46]; p  = 0.04). Conclusion: Aerobic dance significantly improves global cognitive function and memory in older adults with MCI. In addition, it also benefits executive function. However, due to the limitations as the review states, more randomized controlled trials with better study design and larger sample sizes should be conducted in the future research to make it much clearer. Show more

Keywords: Aerobic dance, cognition, executive function, memory, meta-analysis, mild cognitive function, randomized controlled trials

DOI: 10.3233/JAD-190681

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 679-690, 2020

Authors: Maasakkers, Carlijn M. | de Heus, Rianne A.A. | Thijssen, Dick H.J. | Melis, René J.F. | Gardiner, Paul A. | Claassen, Jurgen A.H.R.

Article Type: Research Article

Abstract: Background: Physicians are cautious to prescribe antihypertensive drugs in frail older adults because of the potential adverse effects, especially in those with cognitive complaints. Lifestyle aspects might provide safe targets to lower blood pressure in older adults. Objective: Our goal was to evaluate the associations between activity patterns and blood pressure in memory clinic patients. Methods: We used an observational cross-sectional study to measure activity patterns with the ActivPAL accelerometer, and simultaneous home blood pressure levels in memory clinic patients (age range 51–87 years old). Office blood pressure was assessed during routine clinical practice. …Results: 41 patients (mean age of 74.3 (7.7) years of age, 46% female) were included. Sedentary parameters were associated with higher mean home blood pressure, with the strongest correlation between more prolonged sitting bouts and higher SBP (r  = 0.58, p  < .0001). Physical activity parameters were negatively associated with mean home blood pressure. Adjusted regression estimates remained significant, showing, e.g., a 4.5 (95% CI = 1.6;7.4) mmHg increase in SBP for every hour of sitting per day and a –1.0 (95% CI = –1.8;–0.2) mmHg decrease in DBP for every additional 1000 steps per day. No strong correlations were found between any of the activity pattern variables and office blood pressure. Conclusion: Associations between activity pattern variables and blood pressure were only found with home blood pressure measurements, not with office measurements. Longitudinal evaluations of these associations are now needed to explore if reducing prolonged sedentary bouts and increasing step count indeed serve as safe targets to lower blood pressure. Show more

Keywords: Blood pressure, cognitive decline, dementia, hypertension, physical activity, sedentary behavior

DOI: 10.3233/JAD-191310

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 691-697, 2020

Authors: Gardner, Raquel C. | Rivera, Ernesto | O’Grady, Megan | Doherty, Colin | Yaffe, Kristine | Corrigan, John D. | Bogner, Jennifer | Kramer, Joel | Wilson, Fiona

Article Type: Research Article

Abstract: Background: Traumatic brain injury (TBI) is an established risk factor for dementia but mechanisms are uncertain. Accurate TBI exposure classification is critical for cognitive aging research studies seeking to discover mechanisms and treatments of post-TBI dementia. Brief TBI screens, commonly used in epidemiological studies of cognitive aging, are insensitive, leading to exposure mis-classification. Comprehensive TBI interviews, while more sensitive, may be impractical. Objective: We aimed to develop and validate a scalable, self-administered, comprehensive, web-based, TBI exposure survey for use in international cognitive aging research. Methods: We adapted a gold-standard comprehensive TBI interview (the Ohio State University …TBI Identification Method; OSU TBI-ID) into a self-administered web-based survey for older adults (Older Adult modification of the OSU TBI-ID; OA OSU TBI-ID). We assessed reliability of our web-based survey versus the gold-standard interview among 97 older adults with normal cognition and mild cognitive impairment (MCI). In addition, we assessed sensitivity of the National Alzheimer’s Coordinating Center Uniform Data Set (NACC UDS) brief TBI screen versus the interview among 70 older adults with normal cognition. Results: Our OA OSU TBI-ID web-based survey had good to excellent reliability versus the interview (κ 0.66–0.73; ICCs 0.68–0.81) even among the sub-set with MCI (κ 0.74–0.88; ICCs 0.76–0.85), except for several age-at-injury variables. The NACC UDS brief TBI screen missed 50% of TBI exposures identified using the OSU TBI-ID interview. Conclusion: The OSU TBI-ID interview and web-based survey may facilitate more accurate TBI exposure classification in cognitive aging research thereby accelerating discovery of targetable mechanisms of post-TBI dementia. Show more

Keywords: Clinical research, cognitive aging, reliability, screening, traumatic brain injury, validation

DOI: 10.3233/JAD-191138

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 699-711, 2020