Journal of Alzheimer's Disease - Volume 88, issue 2

Authors: Nakanishi, Miharu | Yamasaki, Syudo | Ando, Shuntaro | Endo, Kaori | Richards, Marcus | Hiraiwa-Hasegawa, Mariko | Kasai, Kiyoto | Nishida, Atsushi

Article Type: Research Article

Abstract: Background: Middle-aged adults may be the ideal target group for dementia-related stigma reduction interventions to encourage the utilization of services among those who may become family caregivers. Neighborhood social cohesion may diminish dementia-related stigma, particularly in terms of perceived public attitudes. The COVID-19 pandemic can further negatively impact perceived public stigma. Objective: To investigate the association between neighborhood social cohesion and dementia-related stigma during the pre- and current COVID-19 period. Methods: We employed a cross-sectional design using data from a large population-based cohort, the Tokyo Teen Cohort, in Japan. Overall, 2,469 mothers of 16-year-old adolescents self-completed …a questionnaire comprising nine dementia-related stigma questions evaluating perceived public and personal attitudes. Neighborhood social cohesion was assessed using a five-item instrument. The participants were divided into two groups according to the time of assessment: prior to the pandemic’s onset (February 2019–March 2020) and during the pandemic (April 2020–July 2021). A multiple regression analysis of stigma was performed using neighborhood social cohesion as an independent variable, and caring experience, age, educational level, and working status as covariates. Results: Personal and perceived public stigma were significantly lower in participants who perceived greater neighborhood social cohesion. However, level of personal and perceived public stigma did not differ between pre- and during the pandemic period. Conclusion: Neighborhood social cohesion may be a modifiable factor for dementia-related stigma. A localized intervention to enhance social cohesion in the neighborhood community would promote the utilization of services among those who may become family caregivers. Show more

Keywords: Asia, dementia, middle aged, mothers, social stigma

DOI: 10.3233/JAD-220043

Citation: Journal of Alzheimer's Disease, vol. 88, no. 2, pp. 493-502, 2022

Authors: García-Roldán, Ernesto | Arriola-Infante, José Enrique | Méndez-Barrio, Carlota | Montiel-Herrera, Fátima | Mendoza-Vázquez, Gonzalo | Marín-Cabañas, Alba Marta | Rodrigo-Herrero, Silvia | Luque-Tirado, Andrea | Sánchez-Arjona, María Bernal | Maillet, Didier | Franco-Macías, Emilio

Article Type: Research Article

Abstract: Background: TMA-93 examines relational binding using images. The test has been proven to be discriminative for diagnosing early Alzheimer’s disease by biomarkers. Norms for this test are available, but the elderly, at high risk for Alzheimer’s disease, have not yet been widely represented. Objective: To extend normative data on the TMA-93 for people aged 75 and over. Methods: An extension of the Spanish TMA-93 normative study was undertaken. Only cognitively unimpaired people aged 75 and over were included. Age, gender, and educational attainment were registered as socio-demographic variables. Using histograms analysis, median comparisons, and linear regression …analysis, we selected variables that demonstrated influence on TMA-93 total scores and provided percentile-base reference data according to combinations of those variables. Results: We included 431 new participants, resulting in a total sample of 657 individuals (median age = 78, interquartile range = 76–81, range = 75–93). Percentile-base reference data stratified by a combination of age ranges (75–79, n  = 428; and ≥80 years, n  = 229), and educational attainment (< first grade, n  = 253; first grade, n  = 209; > first grade, n  = 195) revealed that participants achieved a minimum TMA-93 total score of 26/30 at the 50th-percentile regardless of stratum. At the 10th-percentile, a maximum of 24/30 was achieved in the more educated stratum contrasting with a minimum of 19/30 in the less educated stratum. Conclusion: Although mitigated by lower levels of education, performance on the TMA-93 is widely preserved in cognitively unimpaired people aged 75 and over. The test could facilitate the screening of elderly patients with memory complaints. Show more

Keywords: Alzheimer’s disease, binding, elderly, illiterate, normative data, TMA-93

DOI: 10.3233/JAD-220099

Citation: Journal of Alzheimer's Disease, vol. 88, no. 2, pp. 503-512, 2022

Authors: Gonzalez-Moreno, Jesús | Satorres, Encarnacion | Soria-Urios, Gema | Meléndez, Juan C.

Article Type: Research Article

Abstract: Background: Cognitive stimulation is one of the non-pharmacological therapies recommended for intervention in dementia, consisting of activities involving different cognitive domains and involving brain activation. New technologies can be very useful in this field, favoring intervention tasks. Objective: The objective of this work is to test the effectiveness of a cognitive stimulation intervention mediated with new technologies on a group of people with moderate dementia. Methods: This is a quantitative, quasi-experimental study with a control and treatment group, with three measurement times (pre, post, and follow-up months after the end of the intervention). Ninety-eight subjects with …moderate dementia were randomly assigned to the treatment group (N = 50) and the control group (N = 48). The treatment group received 16 intervention sessions including attention, executive function, and memory tasks, which were presented using new technologies and the activity was conducted in a group setting. Control group remained on a waiting list. The evaluators did not know which group each subject belonged to. All participants were assessed with a battery of neuropsychological tests. Results: The results show an improvement in post-intervention outcomes in the treatment group compared to the control group on cognitive variables. No differences were found in mood depression. These results fade overtime after a few months without intervention. Conclusion: This type of intervention is useful to maintain cognitive functioning using new technologies and in a group setting, which favors the intervention. The improvements of the intervention disappear at follow-up, which would indicate the need to maintain the intervention over time. Show more

Keywords: Cognitive function, dementia, intervention, new technologies

DOI: 10.3233/JAD-220245

Citation: Journal of Alzheimer's Disease, vol. 88, no. 2, pp. 513-519, 2022

Authors: Fowler, Mackenzie E. | Wright, Nicole C. | Triebel, Kristen | Rocque, Gabrielle B. | Irvin, Marguerite R. | Kennedy, Richard E.

Article Type: Research Article

Abstract: Background: Cancer-related cognitive impairment (CRCI), a frequent effect of cancer and its treatments, shares common cognitive symptoms with dementia syndromes. Cross-sectional studies demonstrate an inverse relationship between cancer and dementia. However, the longitudinal relationship between dementia decline and cancer has not been investigated. Objective: To evaluate the association between cancer and longitudinal progression of dementia. Methods: We extracted electronic health record data from July 2003 to February 2020 from a single academic medical center. We identified dementia and cancer history prior to dementia using ICD-9/10 codes. We measured cognitive decline with the Alabama Brief Cognitive Screener …(ABCs). We used adjusted linear mixed models to estimate baseline cognition and rate of progression by cancer history, including differences by race. Results: The study included 3,809 participants with dementia, of which 672 (17.6%) had cancer history. Those with cancer history had higher baseline cognition (β: 1.07, 95% CI: 0.45, 1.69), but similar rate of decline. Non-Hispanic Blacks had lower cognitive scores at baseline and throughout follow-up regardless of cancer status compared to non-Hispanic Whites and other races/ethnicities with and without cancer history. Conclusion: In this longitudinal retrospective study, participants with cancer history demonstrate better cognition at dementia diagnosis and no difference in cognitive decline than those without cancer history. Smoking and comorbidities attenuate this association and results indicate non-Hispanic Blacks have worse cognitive outcomes in dementia regardless of cancer history than other race/ethnicity groups. Further exploration of the role of smoking, comorbidities, and race/ethnicity on cancer and dementia-related cognitive decline is needed. Show more

Keywords: Aging, cancer, cognitive dysfunction, dementia

DOI: 10.3233/JAD-220054

Citation: Journal of Alzheimer's Disease, vol. 88, no. 2, pp. 521-535, 2022

Authors: Tsiakiri, Anna | Vlotinou, Pinelopi | Terzoudi, Aikaterini | Heliopoulos, Ioannis | Vadikolias, Konstantinos

Article Type: Research Article

Abstract: Background: Prolonged periods of social deprivation, such as COVID-19-related lockdowns, are associated with deleterious effects on cognitive functions. Objective: The aim of this study was to gauge the effect of prolonged social isolation on the cognitive function of older adults with neurocognitive disorders. Methods: We recruited 125 older adults with minor or major neurocognitive disorders divided into two groups. The control group was tested at the first period of the study (October 2018–May 2019), whereas the experimental group was evaluated at the second chronological period of the study (October 2020–May 2021) during the second wave of …COVID-19. Neuropsychological tests were performed at baseline and six months after baseline. Results: In the control group, significant changes in the scores from the Montreal Cognitive Assessment (MoCA; p  = 0.049) and the Functional Rating Scale for Symptoms of Dementia (FRSSD; p  = 0.005) were found between baseline and follow-up assessments, whereas no changes were identified in Mini-Mental State Examination (MMSE; p  = 0.229) and Geriatric Depression Scale (GDS; p  = 0.619) scores. In the experimental group, the scores from all neuropsychological tests (MoCA, MMSE, GDS, and FRSSD; p  < 0.001 for all) were significantly different at follow-up when compared with those at baseline measurements. Moreover, significant deterioration of specific functions assessed in MMSE and FRSSD was detected, especially in the experimental group. Conclusion: This study highlights cognitive functions directly affected by social deprivation of individuals with neurocognitive disorders. The findings can be used in the rehabilitation from confinement and its negative consequences. Show more

Keywords: Cognitive functions, COVID-19, emotional status, neurocognitive disorders

DOI: 10.3233/JAD-220118

Citation: Journal of Alzheimer's Disease, vol. 88, no. 2, pp. 537-547, 2022

Authors: Araújo, Daniella Castro | Veloso, Adriano Alonso | Gomes, Karina Braga | de Souza, Leonardo Cruz | Ziviani, Nivio | Caramelli, Paulo | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: A cheap and minimum-invasive method for early identification of Alzheimer’s disease (AD) pathogenesis is key to disease management and the success of emerging treatments targeting the prodromal phases of the disease. Objective: To develop a machine learning-based blood panel to predict the progression from mild cognitive impairment (MCI) to dementia due to AD within a four-year time-to-conversion horizon. Methods: We created over one billion models to predict the probability of conversion from MCI to dementia due to AD and chose the best-performing one. We used Alzheimer’s Disease Neuroimaging Initiative (ADNI) data of 379 MCI individuals …in the baseline visit, from which 176 converted to AD dementia. Results: We developed a machine learning-based panel composed of 12 plasma proteins (ApoB, Calcitonin, C-peptide, CRP, IGFBP-2, Interleukin-3, Interleukin-8, PARC, Serotransferrin, THP, TLSP 1-309, and TN-C), and which yielded an AUC of 0.91, accuracy of 0.91, sensitivity of 0.84, and specificity of 0.98 for predicting the risk of MCI patients converting to dementia due to AD in a horizon of up to four years. Conclusion: The proposed machine learning model was able to accurately predict the risk of MCI patients converting to dementia due to AD in a horizon of up to four years, suggesting that this model could be used as a minimum-invasive tool for clinical decision support. Further studies are needed to better clarify the possible pathophysiological links with the reported proteins. Show more

Keywords: Alzheimer’s disease, artificial intelligence, biomarkers, machine learning, proteomics

DOI: 10.3233/JAD-220256

Citation: Journal of Alzheimer's Disease, vol. 88, no. 2, pp. 549-561, 2022

Authors: Wang, Yilin | Li, Lei | Zhao, Xiaodong | Sui, Shaomei | Wang, Qi | Shi, Guizhi | Xu, Huilian | Zhang, Xiujun | He, Yan | Gu, Jinsong

Article Type: Research Article

Abstract: Background: Understanding the relationship between Alzheimer’s disease (AD) and intestinal flora is still a major scientific topic that continues to advance. Objective: To determine characterized changes in the intestinal microbe community of patients with mild AD. Methods: Comparison of the 16S ribosomal RNA (rRNA) high-throughput sequencing data was obtained from the Illumina MiSeq platform of fecal microorganisms of the patients and healthy controls (HC) which were selected from cohabiting caregivers of AD patients to exclude environmental and dietary factors. Results: We found that the abundance of several bacteria taxa in AD patients was different …from that in HC at the genus level, such as Anaerostipes , Mitsuokella , Prevotella , Bosea , Fusobacterium , Anaerotruncus , Clostridium , and Coprobacillus . Interestingly, the abundance of Akkermansia , an emerging probiotic, increased significantly in the AD group compared with that in the HC group. Meanwhile, the quantity of traditional probiotic Bifidobacteria of the AD group also rose. Conclusion: These alterations in fecal microbiome of the AD group indicate that patients with mild AD have unique gut microbial characteristics. These specific AD-associated intestinal microbes could serve as novel potential targets for early intervention of AD. Show more

Keywords: Akkermansia , Bifidobacteria , intestinal microflora, mild Alzheimer’s disease, therapeutic targets

DOI: 10.3233/JAD-220076

Citation: Journal of Alzheimer's Disease, vol. 88, no. 2, pp. 563-575, 2022

Authors: Wessels, Alette M. | Belger, Mark | Johnston, Joseph A. | Yu, Youying | Rentz, Dorene M. | Dowsett, Sherie A. | Chandler, Julie

Article Type: Research Article

Abstract: Background: The integrated Alzheimer’s Disease Rating Scale (iADRS) is a validated cognitive/functional composite that effectively captures cognitive and functional decline over a broad spectrum of disease. The clinical meaningfulness of change on iADRS can be supported by establishing an association with changes on important health outcome measures. Objective: To evaluate the relationship between change on the iADRS and changes in health outcomes in individuals with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD), or mild or moderate AD dementia using placebo data from four AD clinical trials and data from one AD observational study. Methods: …Analysis of covariate (ANCOVA) models were used to estimate the relationship between 18-month change on the iADRS and changes on health outcome measures (related to cost, quality of life, and caregiver burden). The regression coefficients for the iADRS were used to compute impact of natural disease progression and disease-modifying treatment on health outcomes. Additional ANCOVAs were conducted to understand whether cognition and/or function was the underlying explanation of any association between iADRS and health outcome change. Results: Across datasets and disease stages, a worsening on the iADRS was significantly associated with increased societal costs, caregiver burden (time and distress) and worsening in measures of patient quality of life. Conclusion: Decline on the iADRS was associated with worsening in health outcome measures. These findings suggest that the iADRS can be used in clinical trials as a proxy measure of clinically meaningful outcomes of AD progression. Show more

Keywords: Alzheimer’s disease, care burden, global burden of disease, outcome assessment (health care), outcome measures, patient relevant outcome

DOI: 10.3233/JAD-220303

Citation: Journal of Alzheimer's Disease, vol. 88, no. 2, pp. 577-588, 2022

Authors: Wang, Qing | Shi, Yachen | Qi, Xinyang | Qi, Lingyu | Chen, Xiang | Shi, Jingping | Xie, Chunming | Zhang, Zhijun

Article Type: Research Article

Abstract: Background: Platelet proteins may be associated with Alzheimer’s disease (AD) pathology. Objective: To investigate the relationship between platelet proteins and cerebrospinal fluid (CSF) biomarkers of AD and cognition in individuals with memory decline to identify effective screening methods for detecting the early stages of the disease. Methods: We classified 68 participants with subjective memory decline according to the ATN framework determined by CSF amyloid-β (A), CSF p-tau (T), and t-tau (N). All participants underwent Mini-Mental State Examination (MMSE) and platelet-related protein content testing. Results: Eighteen participants had normal AD biomarkers (NCs), 24 subjects had …non-AD pathologic changes (non-AD), and 26 subjects fell within the Alzheimer’s continuum (AD). The platelet amyloid-β protein precursor (AβPP) ratio in the AD group was significantly lower than in the non-AD and NCs groups, and positively correlated with MMSE scores and CSF amyloid-β42 level, which could affect MMSE scores through CSF amyloid-β42 . Levels of platelet phosphorylated-tau 231 and ser396/404 phosphorylated tau were elevated in both AD and non-AD compared to NCs. Additionally, the receiver operating characteristic analysis demonstrated that the platelet AβPP ratio was a sensitive identifier for differentiating the AD from NCs (AUC = 0.846) and non-AD (AUC = 0.768). And ser396/404 phosphorylated tau could distinguish AD from NCs. Conclusion: Our study was the first to find an association between platelet AβPP ratio and CSF biomarkers of AD, which contribute to the understanding of the peripheral changes in AD. These findings may help to discover potential feasible and effective screening tools for AD. Show more

Keywords: Alzheimer’s disease, amyloid-β protein precursor ratio, ATN framework, cerebrospinal fluid, platelet

DOI: 10.3233/JAD-220122

Citation: Journal of Alzheimer's Disease, vol. 88, no. 2, pp. 589-599, 2022

Authors: Shinagawa, Shunichiro | Kawakami, Ito | Takasaki, Emi | Shigeta, Masahiro | Arai, Tetsuaki | Ikeda, Manabu

Article Type: Research Article

Abstract: Background: It is important to make accurate clinical diagnosis of frontotemporal lobar degeneration (FTLD), which in turn, leads to future therapic approaches. The FTLD cases are frequently inaccurately identified, but the frequency of this misidentification according to the underlying pathological subtypes is still unclear. Objective: We aimed to quantify the accuracy of behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA) diagnoses by both the patients’ referring physicians and hospital expert psychiatrists, and we investigated whether the physicians’ and psychiatrists’ diagnostic patterns are associated with a specific neuropathology. Methods: We retrospectively analyzed the …cases of a series of Japanese patients with pathologically diagnosed FTLD (n  = 55): the bvFTD group (n  = 47) consisted of patients with FTLD-tau (n  = 20), FTLD-TDP (TAR DNA-binding protein of 43-kDA) (n  = 19), and FTLD-FUS (fused in sarcoma) (n  = 8). The svPPA patients (n  = 8) all had FTLD-TDP. Results: Only 31% of the patients’ referring physicians mentioned FTD syndrome. The referring psychiatrists and neurologists showed similar diagnostic accuracy. High diagnostic accuracy was observed for the TDP pathology group (mainly svPPA patients). The FTLD-FUS patients were more likely to be diagnosed as having a psychiatric disorder by referring physicians. The hospital expert psychiatrists’ accuracy for identifying FTLD-tau pathology was low. Conclusion: The results of our analyses revealed a specific diagnostic pattern associated with particular FTLD pathological subtypes, which will help to improve non-specialists’ diagnostic ability. Show more

Keywords: Frontotemporal dementia, frontotemporal lobar degeneration, hospital expert psychiatrist, misdiagnosis, referring physician, semantic variant

DOI: 10.3233/JAD-215516

Citation: Journal of Alzheimer's Disease, vol. 88, no. 2, pp. 601-608, 2022