Journal of Alzheimer's Disease - Volume Pre-press, issue Pre-press

Authors: Almansoub, Hasan A.M.M. | Tang, Hui | Wu, Ying | Wang, Ding-Qi | Mahaman, Yacoubou Abdoul Razak | Salissou, Maibouge Tanko Mahamane | Lu, Youming | Hu, Fan | Zhou, Lan-Ting | Almansob, Yusra A.M. | Liu, Dan

Article Type: Research Article

Abstract: Neurotoxicity is one of the major pathological changes in multiple neurological disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), the second popular neurodegenerative disease in aged people. It is known that the AD and PD share the similar neuropathological hallmarks, such as the oxidative stress, loss of specific neurons, and aggregation of specific proteins. However, there are no effective therapeutic drugs for both AD and PD yet. Oxytocin (OXT) is a small peptide with 9 amino acids that is neuroprotective to many neurological disorders. Whether OXT administration confers neuroprotection to 1-methyl-4-phenyl-1, 2, 3, 6- tetrahydropyridine (MPTP)-induced neurotoxicity in mice …are still not known. In this study, we first found that the OXT levels are decreased in MPTP mice. Supplementation with OXT effectively rescues the locomotor disabilities and anxiety-like behaviors in MPTP mice. OXT also alleviates the hyperphosphorylation of α -synuclein at S129 site and the loss of dopaminergic neurons in the substantia nigra pars compacta, as well as the oxidative stress in the MPTP mice, and alleviates both oxidative stress and cell cytotoxicity in vitro . Furthermore, we found that OXT could inhibit the miR-26a/DAPK1 signal pathway in MPTP mice. In summary, our study demonstrates protective effects of OXT in MPTP mice and that miR-26a/DAPK1 signaling pathway may play an important role in mediating the protection of OXT. Show more

Keywords: Alpha-synuclein, behavior deficit, MPTP, neurotoxicity, oxidative stress, oxytocin, Parkinson’s disease

DOI: 10.3233/JAD-191091

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-19, 2020

Authors: Marelli, Cecilia | Hourregue, Claire | Gutierrez, Laure-Anne | Paquet, Claire | Menjot de Champfleur, Nicolas | De Verbizier, Delphine | Jacob, Melissa | Dubois, Jonathan | Maleska, Aleksandra Maceski | Hirtz, Christophe | Navucet, Sophie | Bennys, Karim | Dumurgier, Julien | Cognat, Emmanuel | Berr, Claudine | Magnin, Eloi | Lehmann, Sylvain | Gabelle, Audrey

Article Type: Research Article

Abstract: Background: Memory troubles and hippocampal atrophy are considered more frequent and focal atrophy less severe in late-onset (>65 years) than in presenile behavioral variant frontotemporal dementia (bvFTD). Objective: To compare cerebrospinal fluid (CSF) and plasma biomarkers in late-onset and presenile bvFTD. Methods: Multicentric retrospective study (2007-2017) on patients with clinical diagnosis of bvFTD. Results: This study included 44 patients (67%) with presenile and 22 (33%) with late-onset bvFTD (comparable mean disease duration; n  = 11 with causal mutations). Hippocampal atrophy was more frequent (80% versus 25.8%) and severe in late-onset bvFTD (median Scheltens score: 3 …[0–4] versus 1 [0–3]), without difference after adjustment for age. Lobar atrophy and focal hypometabolism/hypoperfusion were not different between groups. The median CSF Aβ1-42 and phosphorylated tau (P-tau) concentrations were in the normal range and comparable between groups. Axonal neurodegeneration biomarkers were within the normal range (CSF T-tau; plasma T-tau in late-onset bvFTD) or higher (plasma neurofilament light chain (NFL); plasma T-tau in presenile bvFTD) than the normal values, but globally not different between bvFTD groups. Plasma glial fibrillary acid protein (GFAP) was strongly increased in both bvFTD groups compared with the values in controls of the same age. Conclusion: The CSF and plasma biomarker profiles did not suggest a more aggressive neurodegeneration in the presenile group (comparable T-tau, NFL, and GFAP levels) or the co-existence of Alzheimer’s disease in the late-onset group (comparable and within normal range CSF Aβ1-42 and P-tau). The severity of the neurodegenerative process seems comparable in presenile and late-onset bvFTD. Show more

Keywords: Biomarkers, cerebrospinal fluid, frontotemporal dementia, glial fibrillary acid protein, late-onset, neurofilament light chain

DOI: 10.3233/JAD-190378

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2020

Authors: Pasha, Evan P. | Rutjes, Elmer | Tomoto, Tsubasa | Tarumi, Takashi | Stowe, Ann | Claassen, Jurgen A.H.R. | Munro Cullum, C. | Zhu, David C. | Zhang, Rong

Article Type: Research Article

Abstract: Background: Vascular dysfunction has been implicated in the onset and progression of Alzheimer’s disease (AD), yet the relationship of arterial stiffening with brain amyloid-β (Aβ) burden in at risk patients is unclear. Objective: We aimed to determine the relationship of aortic and carotid arterial stiffening with Aβ burden in patients with amnestic mild cognitive impairment (aMCI), a proposed transitional stage between normal aging and AD. Methods: Thirty-two older adults with aMCI underwent 18 Florbetapir PET amyloid imaging to ascertain Aβ burden via standardized uptake value ratio (SUVR). Carotid-femoral pulse wave velocity (cfPWV), which reflects aortic stiffness, …and carotid β stiffness index and distensibility, which reflect local cerebral arterial stiffness, thus having direct impact on the cerebral circulation, were measured using applanation tonometry and ultrasonography. Results: Region-of-interest based analysis showed that precuneus and mean cortex Aβ SUVR were correlated positively with carotid β stiffness index and negatively with carotid distensibility after adjusting for age, sex, mean arterial pressure (MAP), pulse pressure (PP), and APOE4 status. Whole-brain voxel-wise analysis showed that Aβ SUVR was positively correlated with carotid β stiffness index, and negatively with carotid distensibility at the precuneus/cingulate gyrus after multiple comparison correction. cfPWV was not correlated with Aβ SUVR. Conclusions: Carotid rather than aortic stiffening is independently associated with brain Aβ burden in patients with aMCI after adjusting for age, sex, MAP, PP, and APOE4 status. These findings provide evidence that arterial stiffening, particularly carotid artery stiffening, may contribute to AD pathology in patients with aMCI. Show more

Keywords: Arterial stiffness, amyloid, mild cognitive impairment, ClinicalTrials.gov identifier: NCT01146717

DOI: 10.3233/JAD-191073

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 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. Pre-press, no. Pre-press, pp. 1-12, 2020

Authors: Sundström, Anna | Sörman, Daniel Eriksson | Hansson, Patrik | Ljungberg, Jessica Körning | Adolfsson, Rolf

Article Type: Short Communication

Abstract:  High mental demands at work was examined as a possible protective factor to reduce the risk of dementia in 1,277 initially dementia-free participants, aged 60 years and older. The cohort was followed for a mean of 13.6 years. During follow-up, 376 participants developed all-cause dementia (Alzheimer’s disease = 199; vascular dementia = 145). The association between mental demands at work and dementia was analyzed with Cox hazard models, adjusted for a range of covariates. The results revealed no significant association between mental demands at work and incidence of dementia. Based on the measures used in this study, it was concluded that high mental demands …at work may not reduce the risk of dementia later on in life. Show more

Keywords: Aging, Alzheimer’s disease, cognitive occupation complexity, cognitive reserve, dementia, mental demands at work, vascular dementia

DOI: 10.3233/JAD-190920

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-6, 2020

Authors: Tabara, Yasuharu | Yamanaka, Mikihiro | Setoh, Kazuya | Segawa, Hiroaki | Kawaguchi, Takahisa | Kosugi, Shinji | Nakayama, Takeo | Matsuda, Fumihiko | the Nagahama Study Group

Article Type: Short Communication

Abstract: Accumulation of advanced glycation end products (AGEs) has been linked with cognitive decline as a risk factor based on the analysis in small populations. We investigated the association between skin autofluorescence of AGEs and global cognitive function in a Japanese older (≥60 years) population (n  = 4,041). The AGEs quartiles were inversely associated with the Revised Hasegawa’s Dementia Scale score (Q1: reference, Q2: β= –0.011, p  = 0.537, Q3: β= –0.043, p  = 0.016, Q4: β= –0.064, p  < 0.001) independent of major risk factors. Accumulation of AGEs was associated with lower cognitive performance in older adults.

Keywords: Advanced glycation end products, cognitive function, epidemiological studies, population at risk

DOI: 10.3233/JAD-190878

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-6, 2020

Authors: Liu, Peng | Zhao, Beiyu | Wei, Meng | Li, Yanbo | Liu, Jie | Ma, Louyan | Shang, Suhang | Huo, Kang | Wang, Jin | Li, Rui | Qu, Qiumin

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is the most common age-associated neurodegenerative disease featured by progressive learning and memory deficit, and Aβ was identified as playing a key role in the process of AD and was theorized to be caused by the imbalance of production and clearance. Increasing evidence suggested an association between sleep deprivation and AD. Our recent study found that chronic sleep restriction (CSR) caused cognitive impairment and Aβ accumulation in rats, but the underlining mechanism was unclear. In the present study, we investigated the effects of inflammation on Aβ accumulation induced by CSR. We found that CSR significantly increased the …expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α ), inducible nitric oxide synthase (iNOS), and nitric oxide (NO) in brain, and the inflammatory factors levels were positively correlated with Aβ42 deposition. Additionally, the inflammatory factors were correlated with BACE1, LRP-1, and RAGE levels in both the hippocampus and the prefrontal cortex. Furthermore, the plasma levels of IL-1β, TNF-α , and NO were elevated after CSR, and the concentration of plasma inflammatory mediators were correlated with plasma levels of sLRP1 and sRAGE. These results suggested that the inflammation in brain and plasma might be involved in the CSR-induced Aβ accumulation. Show more

Keywords: Alzheimer’s disease, amyloid-β, chronic sleep restriction, inflammation, risk factor

DOI: 10.3233/JAD-191317

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-15, 2020

Authors: Silva, Dina | Cardoso, Sandra | Guerreiro, Manuela | Maroco, João | Mendes, Tiago | Alves, Luísa | Nogueira, Joana | Baldeiras, Inês | Santana, Isabel | de Mendonça, Alexandre

Article Type: Research Article

Abstract: Background: Diagnosis of Alzheimer’s disease (AD) confirmed by biomarkers allows the patient to make important life decisions. However, doubt about the fleetness of symptoms progression and future cognitive decline remains. Neuropsychological measures were extensively studied in prediction of time to conversion to dementia for mild cognitive impairment (MCI) patients in the absence of biomarker information. Similar neuropsychological measures might also be useful to predict the progression to dementia in patients with MCI due to AD. Objective: To study the contribution of neuropsychological measures to predict time to conversion to dementia in patients with MCI due to AD. …Methods: Patients with MCI due to AD were enrolled from a clinical cohort and the effect of neuropsychological performance on time to conversion to dementia was analyzed. Results: At baseline, converters scored lower than non-converters at measures of verbal initiative, non-verbal reasoning, and episodic memory. The test of non-verbal reasoning was the only statistically significant predictor in a multivariate Cox regression model. A decrease of one standard deviation was associated with 29% of increase in the risk of conversion to dementia. Approximately 50% of patients with more than one standard deviation below the mean in the z score of that test had converted to dementia after 3 years of follow-up. Conclusion: In MCI due to AD, lower performance in a test of non-verbal reasoning was associated with time to conversion to dementia. This test, that reveals little decline in the earlier phases of AD, appears to convey important information concerning conversion to dementia. Show more

Keywords: Alzheimer’s disease (AD), amyloid-β, cognitive impairment, dementia, mild cognitive impairment due to AD, neuropsychological assessment, prodromal AD, Raven Coloured Progressive Matrices

DOI: 10.3233/JAD-191133

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 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. Pre-press, no. Pre-press, pp. 1-9, 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. Pre-press, no. Pre-press, pp. 1-10, 2020