Journal of Alzheimer's Disease - Volume 88, issue 1

Authors: Mandal, Pravat K. | Dwivedi, Divya | Shukla, Deepika | Samkaria, Avantika | Roy, Rimil Guha | Arora, Yashika | Jindal, Komal

Article Type: Research Article

Abstract: Oxidative stress (OS) is a critical factor in the pathogenesis of Alzheimer’s disease (AD). Elevated OS in AD lowers the level of glutathione (GSH), a brain antioxidant. Currently, GSH is under examination in the clinical population for understanding its association with oxidative load in AD research. Significant depletion in hippocampal GSH, as observed using in vivo magnetic resonance spectroscopy (MRS), reportedly correlates with cognitive impairment in AD. Alterations in cellular-energy metabolism and increased hippocampal pH have also been reported in AD. Hence, this combined molecular interplay between hippocampal GSH and pH must be studied longitudinally for advancing AD research. …Herein, we propose a schematic model depicting the molecular events in AD pathogenesis and provide a possible link between OS, GSH depletion, and pH alterations in the hippocampus. The model would further potentiate the need for in vivo longitudinal studies to confirm the interlinked mechanism between OS, hippocampal GSH depletion, and pH increment in an AD patient brain. Show more

Keywords: cognitive dysfunction, glutathione, hippocampus, magnetic resonance spectroscopy, oxidative stress, pH

DOI: 10.3233/JAD-215729

Citation: Journal of Alzheimer's Disease, vol. 88, no. 1, pp. 1-6, 2022

Authors: Fohner, Alison E. | Sitlani, Colleen M. | Buzkova, Petra | Doyle, Margaret F. | Liu, Xiaojuan | Bis, Joshua C. | Fitzpatrick, Annette | Heckbert, Susan R. | Huber, Sally A. | Kuller, Lewis | Longstreth, William T. | Feinstein, Matthew J. | Freiberg, Matthew | Olson, Nels C. | Seshadri, Sudha | Lopez, Oscar | Odden, Michelle C. | Tracy, Russell P. | Psaty, Bruce M. | Delaney, Joseph A. | Floyd, James S.

Article Type: Short Communication

DOI: 10.3233/JAD-220091

Citation: Journal of Alzheimer's Disease, vol. 88, no. 1, pp. 7-15, 2022

Authors: Wang, Wendy | Gottesman, Rebecca F. | Meyer, Michelle L. | Hughes, Timothy M. | Sullivan, Kevin J. | Wong, Dean F. | Lakshminarayan, Kamakshi | Lutsey, Pamela L.

Article Type: Short Communication

Abstract: We assessed whether carotid intima-media thickness (cIMT) is prospectively associated with amyloid-β (Aβ). 332 nondemented Atherosclerosis Risk in Communities Study participants with carotid ultrasounds (1990–1992) and PET scans (2012–2014) were studied. Participants in the highest (versus lowest) cIMT tertile had 2.17 times the odds of elevated Aβ (95% CI: 1.15–4.11), after demographic and APOE ɛ4 adjustments. An interaction with APOE ɛ4 was observed (p  = 0.02). Greater cIMT was associated with elevated Aβ independent of vascular risk factors among those with ≥1 APOE ɛ4 allele, but not in noncarriers. In this cohort, higher cIMT was associated with Aβ …deposition 22 years later, particularly among APOE ɛ4 carriers. Show more

Keywords: Alzheimer’s disease, amyloid-β, carotid intima-media thickness, carotid ultrasound, florbetapir PET

DOI: 10.3233/JAD-215671

Citation: Journal of Alzheimer's Disease, vol. 88, no. 1, pp. 17-22, 2022

Authors: Umegaki, Hiroyuki | Suzuki, Yusuke | Komiya, Hitoshi | Watanabe, Kazuhisa | Nagae, Masaaki | Yamada, Yosuke

Article Type: Short Communication

Abstract: Quality of life (QOL) was assessed using the EQ-5D twice in 1 year in 57 older community-dwelling people (age 79.1±5.9 years) with mild cognitive impairment in a memory clinic. Screening for sarcopenia at the initial assessment revealed 40.1% of participants (23/57) were sarcopenic. QOL declined in 33.3% of participants (19/57) after around 1 year. Multiple logistic regression analysis showed that sarcopenia was associated with a decline in QOL around 1 year after initial assessment. Sarcopenia may be a risk factor for decline in QOL in older people with mild cognitive impairment.

Keywords: Appendicular muscle mass, EQ-5D, gait, grip, mild cognitive impairment, quality of life, sarcopenia

DOI: 10.3233/JAD-220123

Citation: Journal of Alzheimer's Disease, vol. 88, no. 1, pp. 23-27, 2022

Authors: Narukawa, Masataka | Mori, Yuko | Nishida, Riko | Takahashi, Suzuka | Saito, Takashi | Saido, Takaomi C. | Misaka, Takumi

Article Type: Short Communication

Abstract: Using an amyloid precursor protein (App ) gene knock-in (KI) mouse of Alzheimer’s disease (AD), we investigated the expression of olfactory-related genes in olfactory impairment caused by AD. We observed the change in olfactory behavior in the App -KI mice. There was no significant difference, however, in the mRNA expression levels of olfactory-related genes between the olfactory epithelia of wild-type (WT) and App -KI mice. Amyloid-β deposition was confirmed throughout the olfactory pathway in App -KI mice, but not in WT mice. These show that the change in olfactory behavior in the App -KI mice might cause by the impairment …of the olfactory pathway. Show more

Keywords: App knock-in mice, olfactory epithelium, olfactory impairment, olfactory related genes

DOI: 10.3233/JAD-220213

Citation: Journal of Alzheimer's Disease, vol. 88, no. 1, pp. 29-35, 2022

Authors: Roddick, Kyle M. | Fertan, Emre | Schellinck, Heather M. | Brown, Richard E.

Article Type: Short Communication

Abstract: Although Alzheimer’s disease is most often studied in terms of memory impairments, olfactory dysfunction begins in the early stages. We tested olfactory learning, sensitivity, and response bias using signal detection methods in 12-month-old male and female 5xFAD mice and their wildtype controls in the operant olfactometer. Odor detection was not reduced in the 5xFAD mice, but learning was, which was worse in female 5xFAD mice than in males. Female mice were more conservative in their response strategy. Signal detection analysis allows us to discriminate between cognitive and sensory deficits of male and female mouse models of AD.

Keywords: Accuracy, Alzheimer model mice, false alarms, olfactory learning, response bias, sensitivity, signal detection

DOI: 10.3233/JAD-220049

Citation: Journal of Alzheimer's Disease, vol. 88, no. 1, pp. 37-44, 2022

Authors: Vásquez, Priscilla M. | Tarraf, Wassim | Li, Yuyi | Jenkins, Derek | Soria-Lopez, Jose A. | Zlatar, Zvinka Z. | Marquine, Maria J. | Stickel, Ariana M. | Estrella, Mayra L. | Gallo, Linda C. | Lipton, Richard B. | Isasi, Carmen R. | Cai, Jianwen | Zeng, Donglin | Daviglus, Martha L. | Schneiderman, Neil | González, Hector M.

Article Type: Research Article

Abstract: Background: Population-based studies typically rely on self-reported medical diagnosis (SRMD) of mild cognitive impairment (MCI)/dementia; however, links to objective neurocognitive function have not been established. Objective: Examine the association between SRMD of MCI/dementia and objective neurocognitive function among Hispanic/Latino adults. Methods: We conducted a case-control study using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) baseline data and its ancillary SOL-Investigation of Neurocognitive Aging (SOL-INCA) at visit 2. Hispanic/Latino adults aged 50 years and older (n  = 593) were administered neurocognitive tests: the Six-Item Screener (SIS), Brief-Spanish English Verbal Learning Test (B-SVELT Sum), B-SVELT Recall, Word Fluency …Test (WF), Digit Symbol Substitution Test (DSS), and Trail Making Test A and B. Individual and global neurocognitive function scores were used for analyses. Propensity matching techniques and survey generalized linear regression models were used to compare SRMD of MCI/dementia with demographic, psychological, and cardiovascular risk matched controls. Complex survey design methods were applied. Results: There were 121 cases of SRMD of MCI/dementia and 472 propensity matched controls. At baseline, compared to matched controls, cases showed no differences in neurocognitive function (p  > 0.05). At SOL-INCA visit 2, cases had poorer scores in global neurocognitive function (p  < 0.05), B-SEVLT Sum, B-SEVLT Recall, WF, DSS, and Trail A (p  < 0.01). Conclusion: Observed differences in neurocognitive test scores between SRMD of MCI/dementia cases and matched controls were present at visit 2, but not at baseline in middle-aged and older Hispanic/Latino adults. These findings present initial evidence of the potential utility of SRMD of MCI/dementia in epidemiologic studies, where obtaining confirmation of diagnosis may not be feasible. Show more

Keywords: Cognition, dementia, Hispanic, Latino, mild cognitive impairment, neurocognition

DOI: 10.3233/JAD-215060

Citation: Journal of Alzheimer's Disease, vol. 88, no. 1, pp. 45-55, 2022

Authors: Duan, Lian | Qian, Xueshen | Wang, Qin | Huang, Lan | Ge, Song

Article Type: Research Article

Abstract: Background: With advancements in periodontal medicine, the relationship between periodontitis and systemic diseases has garnered increasing attention. Recently, emerging evidence has indicated that periodontitis may be involved in the pathogenesis of Alzheimer’s disease (AD). Objective: To assess the impact of experimental periodontitis on cognitive function deficits in a rat model of streptozotocin-induced AD and determine the mechanisms underlying these effects. Methods: Rats were randomly assigned to the control (C), experimental periodontitis (P), Alzheimer’s disease (AD), and experimental periodontitis with streptozotocin-induced AD (AD-P) groups. Experimental periodontitis was induced using ligation and coating with Porphyromonas gingivalis . In …the AD-P group, AD was induced by intracerebroventricular injection of streptozotocin after 6 weeks of experimental periodontitis induction. Results: Compared with the group C rats, those in group P exhibited alveolar bone resorption, learning and memory function impairment, and decreased insulin sensitivity and insulin signaling-related protein expression. Glial cell activation and cognitive impairment in streptozotocin-induced groups with significantly increased phosphorylated tau levels were more pronounced relative to the C group. The number of neurons and insulin sensitivity and insulin signaling-related protein expression in group AD-P rats were lower than those in the AD alone group, while the expressions of glial fibrillary acidic protein, tau phosphorylation, interleukin-6, and cyclooxygenase-2 were significantly increased. Conclusion: Periodontitis may be a risk factor exacerbating cognitive deficits in an AD-like neurodegenerative context, possibly by impairing the insulin signaling pathway and stimulating gliosis and neuroinflammation. Show more

Keywords: Alzheimer’s disease, insulin sensitivity, insulin signaling pathway, periodontitis, streptozotocin

DOI: 10.3233/JAD-215720

Citation: Journal of Alzheimer's Disease, vol. 88, no. 1, pp. 57-74, 2022

Authors: Asaoka, Daisuke | Xiao, Jinzhong | Takeda, Tsutomu | Yanagisawa, Naotake | Yamazaki, Takahiro | Matsubara, Yoichiro | Sugiyama, Hideki | Endo, Noemi | Higa, Motoyuki | Kasanuki, Koji | Ichimiya, Yosuke | Koido, Shigeo | Ohno, Kazuya | Bernier, Francois | Katsumata, Noriko | Nagahara, Akihito | Arai, Heii | Ohkusa, Toshifumi | Sato, Nobuhiro

Article Type: Research Article

Abstract: Background: Probiotics have been reported to ameliorate cognitive impairment. Objective: We investigated the effect of the probiotic strain Bifidobacterium breve MCC1274 (A1) in enhancing cognition and preventing brain atrophy of older patients with mild cognitive impairment (MCI). Methods: In this RCT, 130 patients aged from 65 to 88 years old with suspected MCI received once daily either probiotic (B. breve MCC1274, 2×1010 CFU) or placebo for 24 weeks. Cognitive functions were assessed by ADAS-Jcog and MMSE tests. Participants underwent MRI to determine brain atrophy changes using Voxel-based Specific Regional Analysis System for Alzheimer’s …disease (VSRAD). Fecal samples were collected for the analysis of gut microbiota composition. Results: Analysis was performed on 115 participants as the full analysis set (probiotic 55, placebo 60). ADAS-Jcog subscale “orientation” was significantly improved compared to placebo at 24 weeks. MMSE subscales “orientation in time” and “writing” were significantly improved compared to placebo in the lower baseline MMSE (< 25) subgroup at 24 weeks. VSRAD scores worsened in the placebo group; probiotic supplementation tended to suppress the progression, in particular among those subjects with progressed brain atrophy (VOI Z-score ≥1.0). There were no marked changes in the overall composition of the gut microbiota by the probiotic supplementation. Conclusion: Improvement of cognitive function was observed on some subscales scores only likely due to the lower sensitiveness of these tests for MCI subjects. Probiotics consumption for 24 weeks suppressed brain atrophy progression, suggesting that B. breve MCC1274 helps prevent cognitive impairment of MCI subjects. Show more

Keywords: Bifidobacterium, brain atrophy, cognitive function, mild cognitive impairment, probiotics

DOI: 10.3233/JAD-220148

Citation: Journal of Alzheimer's Disease, vol. 88, no. 1, pp. 75-95, 2022

Authors: Drouin, Shannon M. | McFall, G. Peggy | Potvin, Olivier | Bellec, Pierre | Masellis, Mario | Duchesne, Simon | Dixon, Roger A. | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Hippocampal atrophy is a well-known biomarker of neurodegeneration, such as that observed in Alzheimer’s disease (AD). Although distributions of hippocampal volume trajectories for asymptomatic individuals often reveal substantial heterogeneity, it is unclear whether interpretable trajectory classes can be objectively detected and used for prediction analyses. Objective: To detect and predict hippocampal trajectory classes in a computationally competitive context using established AD-related risk factors/biomarkers. Methods: We used biomarker/risk factor and longitudinal MRI data in asymptomatic adults from the AD Neuroimaging Initiative (n  = 351; Mean  = 75 years; 48.7% female). First, we applied latent class growth analyses to …left (LHC) and right (RHC) hippocampal trajectory distributions to identify distinct classes. Second, using random forest analyses, we tested 38 multi-modal biomarkers/risk factors for their relative importance in discriminating the lower (potentially elevated atrophy risk) from the higher (potentially reduced risk) class. Results: For both LHC and RHC trajectory distribution analyses, we observed three distinct trajectory classes. Three biomarkers/risk factors predicted membership in LHC and RHC lower classes: male sex, higher education, and lower plasma Aβ1–42 . Four additional factors selectively predicted membership in the lower LHC class: lower plasma tau and Aβ1–40 , higher depressive symptomology, and lower body mass index. Conclusion: Data-driven analyses of LHC and RHC trajectories detected three classes underlying the heterogeneous distributions. Machine learning analyses determined three common and four unique biomarkers/risk factors discriminating the higher and lower LHC/RHC classes. Our sequential analytic approach produced evidence that the dynamics of preclinical hippocampal trajectories can be predicted by AD-related biomarkers/risk factors from multiple modalities. Show more

Keywords: Biomarker predictions, hippocampal atrophy, latent class growth analyses, random forest analyses, trajectory classes

DOI: 10.3233/JAD-215289

Citation: Journal of Alzheimer's Disease, vol. 88, no. 1, pp. 97-115, 2022