Journal of Alzheimer's Disease - Volume 74, issue 3

Authors: Teimouri, Elham | Rainey-Smith, Stephanie R. | Bharadwaj, Prashant | Verdile, Giuseppe | Martins, Ralph N.

Article Type: Review Article

Abstract:  There is currently no effective treatment for Alzheimer’s disease (AD), the most common form of dementia. It has been proposed, however, that a modest delay in onset can significantly reduce the number of cases. Thus, prevention and intervention strategies are currently the focus of much research. In the search for compounds that potentially confer benefit, the Amla fruit and its extracts have drawn attention. Amla preparations have been used for centuries in traditional Indian medicine systems such as Ayurveda, with various parts of the plant used to treat a variety of diseases. Here we review many animal-based studies, and some …clinical trials, which have shown that Amla, and its extracts, exert many positive effects on dyslipidemia, hyperglycemia, inflammation, oxidative stress, apoptosis, and autophagy, that contribute to AD risk. Collectively, this evidence suggests that Amla may be of value as part of an effective disease-delaying treatment for AD. Show more

Keywords: Amla, Alzheimer’s disease, anti-inflammatory, antioxidant, cardiovascular disease, type 2 diabetes

DOI: 10.3233/JAD-191033

Citation: Journal of Alzheimer's Disease, vol. 74, no. 3, pp. 713-733, 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 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. 74, no. 3, pp. 735-740, 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. 74, no. 3, pp. 741-746, 2020

Authors: Kapoor, Arunima | Bartha, Robert | Black, Sandra E. | Borrie, Michael | Freedman, Morris | Gao, Fuqiang | Herrmann, Nathan | Mandzia, Jennifer | Ozzoude, Miracle | Ramirez, Joel | Scott, Christopher J.M. | Symons, Sean | Fischer, Corinne E. | Frank, Andrew | Seitz, Dallas | Wolf, Michael Uri | Verhoeff, Nicolaas Paul L.G. | Naglie, Gary | Reichman, William | Masellis, Mario | Mitchell, Sara B. | Tang-Wai, David F. | Tartaglia, Maria Carmela | Kumar, Sanjeev | Pollock, Bruce G. | Rajji, Tarek K. | Finger, Elizabeth | Pasternak, Stephen H. | ONDRI Investigators | Swartz, Richard H.

Article Type: Research Article

Abstract: Background/Objective: Structural brain magnetic resonance imaging (MRI) is not mandatory in Alzheimer’s disease (AD) research or clinical guidelines. We aimed to explore the use of structural brain MRI in AD/mild cognitive impairment (MCI) trials over the past 10 years and determine the frequency with which inclusion of standardized structural MRI acquisitions detects comorbid vascular and non-vascular pathologies. Methods: We systematically searched ClinicalTrials.gov for AD clinical trials to determine their neuroimaging criteria and then used data from an AD/MCI cohort who underwent standardized MRI protocols, to determine type and incidence of clinically relevant comorbid pathologies. Results: Of …210 AD clinical trials, 105 (50%) included structural brain imaging in their eligibility criteria. Only 58 (27.6%) required MRI. 16,479 of 53,755 (30.7%) AD participants were in trials requiring MRI. In the observational AD/MCI cohort, 141 patients met clinical criteria; 22 (15.6%) had relevant MRI findings, of which 15 (10.6%) were exclusionary for the study. Discussion: In AD clinical trials over the last 10 years, over two-thirds of participants could have been enrolled without brain MRI and half without even a brain CT. In a study sample, relevant comorbid pathology was found in 15% of participants, despite careful screening. Standardized structural MRI should be incorporated into NIA-AA diagnostic guidelines (when available) and research frameworks routinely to reduce diagnostic heterogeneity. Show more

DOI: 10.3233/JAD-191097

Citation: Journal of Alzheimer's Disease, vol. 74, no. 3, pp. 747-757, 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. 74, no. 3, pp. 759-773, 2020

Authors: Sado, Mitsuhiro | Funaki, Kei | Ninomiya, Akira | Knapp, Martin | Mimura, Masaru

Article Type: Research Article

Abstract: Background: Although the effects of various types of cognitive interventions have been evaluated, effectiveness and cost-saving effect of the combination of the different cognitive interventions is unknown. Objective: This study aimed to evaluate the feasibility of conducting a definitive trial to assess the effectiveness of combined cognitive intervention. Methods: A matched controlled trial of learning therapy (LT), a combination of cognitive training and stimulation, was conducted. The samples were recruited from the nursing homes. Inclusion criteria were as follows: age 65 years or older, clinical diagnosis of dementia, level of activities of daily living at II …or above, Mini-Mental State Examination score between 10 and 26, receiving long-term-care services without history of LT, and provision of written consent. The primary outcomes were safety, validity of eligibility, retention rate, and effect on the functions of daily living represented by Criterion Time for Certification of Needed Long-Term-Care (CT for CNLTC) at 12 months. Cost-benefit analysis was also conducted to assess the cost saving effect of LT. Results: No serious adverse events were detected. The exclusion rate at the screening phase was 5% and the retention rate was 77% at 12 months. LT demonstrated statistically significant improvement in CT for CNLTC at 12 months (Δ =18.8, almost equivalent to “one” degree of the care needed level) and saved the long-term-care cost by JPY 200,000 (USD 1,618). Conclusions: LT is effective for improving care recipients’ level of care needed and has a cost saving effect. A randomized controlled trial is required to verify these findings. Clinical Trial Registration: This study was approved by the ethics committee at Keio University School of Medicine (ID: 20150061). This trial was registered at University hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000018223). Show more

Keywords: Activities of daily living, cost-benefit analysis, cognitive training, dementia, long term care

DOI: 10.3233/JAD-190886

Citation: Journal of Alzheimer's Disease, vol. 74, no. 3, pp. 775-784, 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. 74, no. 3, pp. 785-796, 2020

Authors: Popovac, Aleksandra | Mladenović, Irena | Krunić, Jelena | Trifković, Branka | Todorović, Ana | Milašin, Jelena | Despotović, Nebojša | Stančić, Ivica

Article Type: Research Article

Abstract: Compromised dentition has been suggested to pose a significant risk factor for dementia. It was mainly investigated through insufficient tooth number, disregarding contact between opposing teeth (dental occlusion). The ɛ 4 allele of apolipoprotein (APOE4 ) is the primary genetic marker for the late onset of Alzheimer’s disease (AD). However, APOE4 and dental occlusion have not yet been investigated as possible associated risk factors for AD. The study was aimed to examine the impact of dental status and different APOE gene variants on AD occurrence. Secondly, sociodemographic variables were investigated as factors potentially associated with AD. The case-control …study included two groups: 116 patients with AD (according to the NINDS-ADRDA criteria) and 63 controls (Mini-Mental State Examination scores ≥24). The analysis of APOE gene polymorphism was conducted through PCR reaction. Dental examination included recording of number of teeth, presence of fixed or removable dentures, and number of functional tooth units (FTU). Regression analysis was used to investigate the joint effect of the clinical and genetic variables on AD. Results showed that patients with AD were more often carriers of ɛ 3/ɛ 4 genotype and ɛ 4 allele, had lower number of teeth and FTU, and were less likely to be married, live in home, and had less chronic diseases, compared to the controls. Regression analysis showed that presence of APOE4 allele and the number of total FTU remained associated with AD, even when adjusted for age, sex, and level of education. In conclusion, deficient dental occlusion and presence of APOE4 may independently increase risk for AD. Show more

Keywords: Alzheimer’s disease, apolipoproteins E, dental occlusion, tooth loss

DOI: 10.3233/JAD-191283

Citation: Journal of Alzheimer's Disease, vol. 74, no. 3, pp. 797-802, 2020

Authors: Basta, Maria | Koutentaki, Eirini | Vgontzas, Alexandros | Zaganas, Ioannis | Vogiatzi, Emmanouela | Gouna, Garyfalia | Bourbouli, Mara | Panagiotakis, Symeon | Kapetanaki, Stefania | Fernandez-Mendoza, Julio | Simos, Panagiotis

Article Type: Research Article

Abstract: Background: Patients with dementia report excessive daytime sleep/sleepiness, which is associated with worse cognitive performance. Inflammatory markers may be elevated in patients with dementia and have been proposed as mediators of sleep/sleepiness. Objective: To examine the association of objective daytime napping with cognitive performance and peripheral markers of inflammation in patients with dementia as compared to not cognitively impaired (NCI) controls. Methods: A sub-sample of 46 patients with mild-to-moderate dementia and 85 NCI controls, were recruited from a large, population-based cohort of 3,140 elders (≥60 years) in Crete, Greece. All participants underwent medical history/physical examination, extensive …neuropsychiatric and neuropsychological evaluation, 3-day 24 h actigraphy and a single morning measure of IL-6 and TNFα plasma levels. Comparisons of sleep parameters and inflammation markers between diagnostic groups, and between nappers and non-nappers within each diagnostic group, were conducted using ANCOVA controlling for demographics/related clinical factors. Associations between inflammatory markers, sleep variables, and neuropsychological performance were assessed within each group using partial correlation analysis controlling for confounders. Results: Patients with dementia slept 15 minutes longer during the day than NCI. Within dementia patients, nappers had significantly worse performance on autobiographic memory (p  = 0.002), working memory (p  = 0.007), episodic memory (p  = 0.010), and assessment of daily function (p  = 0.012) than non-nappers. Finally, IL-6 levels were significantly associated with nap duration within dementia patients who napped (r  = 0.500, p  = 0.01). Conclusions: Daytime napping in patients with dementia is associated with worse cognitive performance and increased IL-6 levels. In dementia, objective daytime napping, may be a marker of the severity of the disease. Show more

Keywords: Actigraphy, cognitive performance, cytokines, dementia, inflammation, objective daytime napping

DOI: 10.3233/JAD-190483

Citation: Journal of Alzheimer's Disease, vol. 74, no. 3, pp. 803-815, 2020

Authors: Mariano, Luciano Inácio | Caramelli, Paulo | Guimarães, Henrique Cerqueira | Gambogi, Leandro Boson | Moura, Millena Vieira Brandão | Yassuda, Mônica Sanches | Teixeira, Antônio Lúcio | de Souza, Leonardo Cruz

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) share cognitive and behavioral symptoms, such as apathy. Social cognition measurements are useful in distinguishing bvFTD from AD, but their accuracies may be affected by apathy. Objective: To investigate whether social cognition measurements can distinguish bvFTD from either apathetic or non-apathetic AD patients. Methods: Three groups of participants were enrolled in the present study: bvFTD (n  = 22), AD (n  = 20), and healthy controls (HC, n  = 23). The AD group was divided into apathetic (n  = 10) and non-apathetic (n  = 10). All subjects underwent comprehensive neuropsychological examination, including …the short version of the Social and Emotional Assessment (Mini-SEA), which comprises the facial emotion recognition test and the faux-pas recognition test (Faux-Pas Test). Apathy was assessed according to the Starkstein’s Apathy (SA) Scale. Results: The bvFTD and AD groups did not differ on global cognitive efficiency and on executive functions. In comparison to the whole AD group, bvFTD displayed lower Faux-Pas Test and Mini-SEA scores. Both AD subgroups, apathetic or non-apathetic, exhibited similar performance on all social cognition measurements. In comparison to either apathetic AD or non-apathetic AD, bvFTD patients underperformed on the Faux-Pas Test and on the Mini-SEA. The area under the curve values for the Mini-SEA total score were 0.87 (bvFTD versus AD), 0.90 (bvFTD versus apathetic AD), and 0.83 (bvFTD versus non-apathetic AD). Conclusion: Social cognition tests provide accurate distinction between bvFTD against either apathetic AD or non-apathetic AD. Social cognition measurements did not correlate with apathy severity. Show more

Keywords: Alzheimer’s disease, apathy, frontotemporal dementia, social cognition

DOI: 10.3233/JAD-190861

Citation: Journal of Alzheimer's Disease, vol. 74, no. 3, pp. 817-827, 2020