Journal of Alzheimer's Disease - Volume 96, issue 4

Authors: Briceño, Emily M. | Dhakal, Usha | Sharma, Uttam | Adhikari, Nabin | Pradhan, Meeta S. | Shrestha, Lochana | Jalan, Pankaj | Rai, Janak | Langa, Kenneth M. | Lee, Jinkook | Ghimire, Dirgha | Mendes de Leon, Carlos F.

Article Type: Review Article

Abstract: The population of Nepal is rapidly aging, as in other low and middle-income countries, and the number of individuals living with Alzheimer’s Disease and related dementias (ADRD) is expected to increase. However, information about the neuropsychological assessment of ADRD in Nepal is lacking. We first aimed to examine the needs, challenges, and opportunities associated with the neuropsychological assessment of older adults in Nepal for population-based ADRD ascertainment. Second, we introduce the Chitwan Valley Family Study-Study of Cognition and Aging in Nepal (CVFS-SCAN), which is poised to address these needs, and its collaboration with the Harmonized Cognitive Assessment Protocol (HCAP) international …network. We reviewed the existing literature on the prevalence, risk factors, available neuropsychological assessment instruments, and sociocultural factors that may influence the neuropsychological assessment of older adults for ADRD ascertainment in Nepal. Our review revealed no existing population-based data on the prevalence of ADRD in Nepal. Very few studies have utilized formal cognitive assessment instruments for ADRD assessment, and there have been no comprehensive neuropsychological assessment instruments that have been validated for the assessment of ADRD in Nepal. We describe how the CVFS-SCAN study will address this need through careful adaptation of the HCAP instrument. We conclude that the development of culturally appropriate neuropsychological assessment instruments is urgently needed for the population-based assessment of ADRD in Nepal. The CVFS-SCAN is designed to address this need and will contribute to the growth of global and equitable neuropsychology and to the science of ADRD in low- and middle-income countries. Show more

Keywords: Alzheimer’s disease and related dementias, cognitive aging, cultural neuropsychology, global health, mild cognitive impairment

DOI: 10.3233/JAD-230906

Citation: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1339-1352, 2023

Authors: Grant, William B. | Blake, Steven M.

Article Type: Review Article

Abstract: Diet is an important nonpharmacological risk-modifying factor for Alzheimer’s disease (AD). The approaches used here to assess diet’s role in the risk of AD include multi-country ecological studies, prospective and cross-sectional observational studies, and laboratory studies. Ecological studies have identified fat, meat, and obesity from high-energy diets as important risk factors for AD and reported that AD rates peak about 15–20 years after national dietary changes. Observational studies have compared the Western dietary pattern with those of the Dietary Approaches to Stop Hypertension (DASH), Mediterranean (MedDi), and Mediterranean–DASH Intervention for Neurodegenerative Delay (MIND) diets. Those studies identified AD risk factors …including higher consumption of saturated and total fats, meat, and ultraprocessed foods and a lower risk of AD with higher consumption of fruits, legumes, nuts, omega-3 fatty acids, vegetables, and whole grains. Diet-induced factors associated with a significant risk of AD include inflammation, insulin resistance, oxidative stress, elevated homocysteine, dietary advanced glycation end products, and trimethylamine N -oxide. The molecular mechanisms by which dietary bioactive components and specific foods affect risk of AD are discussed. Given most countries’ entrenched food supply systems, the upward trends of AD rates would be hard to reverse. However, for people willing and able, a low–animal product diet with plenty of anti-inflammatory, low–glycemic load foods may be helpful. Show more

Keywords: Advanced glycation end products, Alzheimer’s disease, dementia, diet, meat, neuroinflammation, obesity, saturated fat, TMAO, ultraprocessed foods

DOI: 10.3233/JAD-230418

Citation: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1353-1382, 2023

Authors: Tao, Shuqi | Fan, Wenyuan | Liu, Jinmeng | Wang, Tong | Zheng, Haoning | Qi, Gaoxiu | Chen, Yanchun | Zhang, Haoyun | Guo, Zhangyu | Zhou, Fenghua

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is currently the most prevalent neurological disease, and no effective and practical treatments and therapies exist. The nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain- containing receptor 3 (NLRP3) inflammasome is vital in the human innate immune response. However, when the NLRP3 inflammasome is overactivated by persistent stimulation, several immune-related diseases, including AD, atherosclerosis, and obesity, result. This review will focus on the composition and activation mechanism of the NLRP3 inflammasome, the relevant mechanisms of involvement in the inflammatory response to AD, and AD treatment targeting NLRP3 inflammasome. This review aims to reveal the pathophysiological mechanism of …AD from a new perspective and provide the possibility of more effective and novel strategies for preventing and treating AD. Show more

Keywords: Alzheimer’s disease, amyloid-β, inhibitors, NLRP3 inflammasome, tau, treatment

DOI: 10.3233/JAD-230567

Citation: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1383-1398, 2023

Authors: Monllor, Paloma | Kumar, Pratyush | Lloret, Mari-Ángeles | Ftara, Artemis | Leon, Jose-Luis | Lopez, Begoña | Cervera-Ferri, Ana | Lloret, Ana

Article Type: Review Article

Abstract: There are several implications of the surge in the incidence of pandemics and epidemics in the last decades. COVID-19 being the most remarkable one, showed the vulnerability of patients with neurodegenerative diseases like Alzheimer’s disease (AD). This review studies the pathological interlinks and triggering factors between the two illnesses and proposes a multifactorial pathway of AD causation due to COVID-19. The article evaluates and describes all the postulated hypotheses which explain the etiology and possible pathogenesis of the disease in four domains: Inflammation & Neurobiochemical interactions, Oxidative Stress, Genetic Factors, and Social Isolation. We believe that a probable hypothesis of …an underlying cause of AD after COVID-19 infection could be the interplay of all these factors. Show more

Keywords: Alzheimer’s disease, inflammation, oxidative stress, SarsCoV-2 infection, social isolation

DOI: 10.3233/JAD-230396

Citation: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1399-1409, 2023

Authors: Zeng, Xiao Xue | Zeng, Jie Bangzhe

Article Type: Review Article

Abstract: The traits of Alzheimer’s disease (AD) include amyloid plaques made of Aβ1-40 and Aβ1-42 , and neurofibrillary tangles by the hyperphosphorylation of tau protein. AD is a complex disorder that is heterogenous in genetical, neuropathological, and clinical contexts. Current available therapeutics are unable to cure AD. Systems medicine is a strategy by viewing the body as a whole system, taking into account each individual’s unique health profile, provide treatment and associated nursing care clinically for the patient, aiming for precision. Since the onset of AD can lead towards cognitive impairment, it is vital to intervene and diagnose early and …prevent further progressive loss of neurons. Moreover, as the individual’s brain functions are impaired due to neurodegeneration in AD, it is essential to reconstruct the neurons or brain cells to enable normal brain functions. Although there are different subtypes of AD due to varied pathological lesions, in the majority cases of AD, neurodegeneration and severe brain atrophy develop at the chronic stage. Novel approaches including RNA based gene therapy, stem cell based technology, bioprinting technology, synthetic biology for brain tissue reconstruction are researched in recent decades in the hope to decrease neuroinflammation and restore normal brain function in individuals of AD. Systems medicine include the prevention of disease, diagnosis and treatment by viewing the individual’s body as a whole system, along with systems medicine based nursing as a strategy against AD that should be researched further. Show more

Keywords: Alzheimer’s disease, gene therapy, synthetic biology, systems medicine

DOI: 10.3233/JAD-230739

Citation: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1411-1426, 2023

Authors: Solis-Urra, Patricio | Rodriguez-Ayllon, María | Álvarez-Ortega, Miriam | Molina-Hidalgo, Cristina | Molina-Garcia, Pablo | Arroyo-Ávila, Cristina | García-Hermoso, Antonio | Collins, Audrey M. | Jain, Shivangi | Gispert, Juan Domingo | Liu-Ambrose, Teresa | Ortega, Francisco B. | Erickson, Kirk I. | Esteban-Cornejo, Irene

Article Type: Systematic Review

Abstract: Background: Accumulation of amyloid-β (Aβ) plaques is one of the main features of Alzheimer’s disease (AD). Physical performance has been related to dementia risk and Aβ, and it has been hypothesized as one of the mechanisms leading to greater accumulation of Aβ. Yet, no evidence synthesis has been performed in humans. Objective: To investigate the association of physical performance with Aβ in humans, including Aβ accumulation on brain, and Aβ abnormalities measured in cerebrospinal fluid (CSF) and blood. Methods: A systematic review with multilevel meta-analysis was performed from inception to June 16th , 2022. Studies were …eligible if they examined the association of physical performance with Aβ levels, including the measure of physical performance as a predictor and the measure of Aβ as an outcome in humans. Results: 7 articles including 2,619 participants were included in the meta-analysis. The results showed that physical performance was not associated with accumulation of Aβ in the brain (ES = 0.01; 95% CI –0.21 to 0.24; I2  = 69.9%), in the CSF (ES = –0.28; 95% CI –0.98 to 0.41; I2  = 91.0%) or in the blood (ES = –0.19; 95% CI –0.61 to 0.24; I2  = 99.75%). Significant heterogeneity was found across the results , which posed challenges in arriving at consistent conclusions; and the limited number of studies hindered the opportunity to conduct a moderation analysis. Conclusions: The association between physical performance and Aβ is inconclusive. This uncertainly arises from the limited number of studies, study design limitations, and heterogeneity of measurement approaches. More studies are needed to determine whether physical performance is related to Aβ levels in humans. Show more

Keywords: Alzheimer’s disease, amyloid, meta-analysis, physical performance

DOI: 10.3233/JAD-230586

Citation: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1427-1439, 2023

Authors: Ly, Maria | Yu, Gary Z. | Chwa, Won Jong | Raji, Cyrus A.

Article Type: Systematic Review

Abstract: Background: Given the advent of large-scale neuroimaging data-driven endeavors for Alzheimer’s disease, there is a burgeoning need for well-characterized neuroimaging databases of healthy individuals. With the rise of initiatives around the globe for the rapid and unrestricted sharing of data resources, there is now an abundance of open-source neuroimaging datasets available to the research community. However, there is not yet a systematic review that fully details the demographic information and modalities actually available in all open access neuroimaging databases around the globe. Objective: This systematic review aims to provide compile a list of MR structural imaging databases encompassing …healthy individuals across the lifespan. Methods: In this systematic review, we searched EMBASE and PubMed until May 2022 for open-access neuroimaging databases containing healthy control participants of any age, race, with normal development and cognition having at least one structural T1-weighted neuroimaging scan. Results: A total of 403 databases were included, for up to total of 48,268 participants with all available demographic information and imaging modalities detailed in Supplementary Table 1 . There were significant trends noted when compiling normative databases for this systematic review, notably that 11.7% of databases included reported ethnicity in their participants, with underrepresentation of many socioeconomic groups globally. Conclusions: As efforts to improve primary prevention of AD may require a broader perspective including increased relevance of earlier stages in life, and strategies in addressing modifiable risk factors may be individualized to specific demographics, improving data characterization to be richer and more rigorous will greatly enhance these efforts. Show more

Keywords: Aging, Alzheimer’s disease, database, neuroimaging, normative, open-access, representation, social determinants of health

DOI: 10.3233/JAD-230738

Citation: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1441-1451, 2023

Authors: Grasso, Stephanie M. | Wagner Rodríguez, Camille A. | Montagut Colomer, Núria | Marqués Kiderle, Sonia-Karin | Sánchez-Valle, Raquel | Santos Santos, Miguel Ángel

Article Type: Review Article

Abstract: Background: Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by speech and/or language impairment with relatively spared cognition. Research investigating behavioral speech-language intervention and methods for cognitive-linguistic assessment in PPA has predominantly centered around monolingual speakers. This gap hinders the widespread adoption of evidence-based approaches and exacerbates the inequities faced by culturally and linguistically diverse populations living with PPA. Objective: This scoping review synthesizes the current evidence for assessment and treatment practices in bilingual PPA as well as the operationalization of bilingualism in PPA. Methods: Arksey & O’Malley’s scoping review methodology was utilized. Information was …extracted from each study and entered into a data-charting template designed to capture information regarding operationalization of bilingualism in PPA and assessment and treatment practices. Results: Of the 16 identified studies, 14 reported the results of assessments conducted in both languages. Three studies reported positive naming treatment outcomes. Thirteen studies included English-speaking participants, revealing linguistic bias. Most studies reported age of acquisition, proficiency, and patterns of language use rather than providing an operational definition for bilingualism. Conclusions: Neither formal assessment measures nor clear guidelines for assessment of bilingual PPA currently exist; however, language-specific measures are emerging. Speech-language intervention in bilingual PPA has been relatively unexplored, representing a significant gap in the literature. In order to improve diagnostic and treatment options for bilingual PPA, targeted efforts to increase representation of bilinguals from various sociocultural contexts, as well as those who speak a variety of language pairs, is necessary. Show more

Keywords: Alzheimer’s disease, aphasia, assessment, bilingualism, cultural and linguistic diversity, dementia, intervention, language, primary progressive aphasia, scoping review, speech-language pathology

DOI: 10.3233/JAD-230673

Citation: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1453-1476, 2023

Authors: Wang, Mu-Cyun | Chiou, Jeng-Min | Chen, Yen-Ching | Chen, Jen-Hau

Article Type: Research Article

Abstract: Background: Previous studies assessing olfactory function and cognition have mostly been cross-sectional, and few have investigated the Asian geriatric population. Objective: To examine the relationships of olfaction with global or domain-specific cognitive function in Taiwanese community-dwelling older adults. Methods: This cohort study (2015–2019) is part of the Taiwan Initiative for Geriatric Epidemiological Research. The Taiwanese version of the Montreal Cognitive Assessment (MoCA-T) and a battery of neuropsychological tests were assessed at baseline and at a two-year follow-up. The cross-culture modified Sniffin’ Sticks Identification Test (SSIT) was utilized to measure olfactory function. Generalized linear mixed models were …used to examine the association of olfaction with cognitive performance over two years. Results: Data were collected from 376 participants (55.1% women), with a mean age of 75.6 years. A one-point decrease in the SSIT score (worsening of olfaction) was associated with worse global cognition (MoCA-T: β ˆ = –0.13), memory ( β ˆ = –0.08 to –0.06), and verbal fluency ( β ˆ = –0.07). Compared with an SSIT score ≥ 11 (normosmia), an SSIT score < 8 (anosmia) was associated with worse global cognition (MoCA-T: β ˆ = –0.99), memory ( β ˆ = –0.48 to –0.42), executive function (Trail Making Test A: β ˆ = –0.36), attention (digit span backward: β ˆ = –0.34), and verbal fluency ( β ˆ = –0.45). After stratified analyses, the associations remained in older adults ≥ 75 years, males, and non-carriers of apolipoprotein E ɛ4 in terms of global cognition, memory, and verbal fluency. Conclusions: Odor identification deficits were associated with poor global or domain-specific cognitive function in a four-year cohort of community-dwelling older adults. Cognitive assessments should be conducted in dementia-free elderly individuals with impaired odor identification. Show more

Keywords: Cognition, Montreal Cognitive Assessment, odor identification, older adults, olfaction

DOI: 10.3233/JAD-230319

Citation: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1477-1488, 2023

Authors: Wang, Xiaoping | Huang, Rui | Huang, Bin | Li, Xiaojia

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is a fatal and debilitating neurodegenerative disease. Sphingosine-1-phosphate receptor 2 (S1PR2), one of the receptors of S1P, is a key regulatory factor for various diseases. Objective: This study aimed to explore the role and possible mechanism of S1PR2 in AD. Methods: S1PR2 expression in the AD mice was detected, and after intervening S1PR2 expression with sh-S1PR2 in AD mice, the behavioral changes, pathological lesions of the hippocampus, autophagy level, and AKT/mTOR pathway activation were analyzed. Furthermore, SH-SY5Y cells were induced by Aβ25-35 to construct an AD cell model, …and the effects of sh-S1PR2 on proliferation, apoptosis, autophagy, and AKT/mTOR pathway of AD cells were investigated. In addition, the effects of pathway inhibitor rapamycin on model cells were further analyzed. Results: The expression of S1PR2 was significantly increased in AD mice, the sh-S1PR2 significantly improved behavioral dysfunction, alleviated pathological injury of the hippocampus, increased the number of neurons, and inhibited Aβ production and p-tau expression, showing a positive effect on the AD pathology. In addition, silencing of S1PR2 expression significantly promoted the autophagy level and inhibited the activation of the AKT/mTOR pathway in AD model mice. In vitro experiments further confirmed that sh-S1PR2 promoted cell proliferation, inhibited apoptosis, relieved cytopathology, promoted autophagy, and inhibited the activation of the AKT/mTOR pathway in the cell model. The use of rapamycin further confirmed the role of AKT/mTOR pathway-mediated autophagy in the regulation of AD by S1PR2. Conclusion: S1PR2 promoted AD pathogenesis by inhibiting autophagy through the activation of AKT/mTOR pathway. Show more

Keywords: AKT/mTOR pathway, Alzheimer’s disease, autophagy, S1PR2

DOI: 10.3233/JAD-230533

Citation: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1489-1504, 2023