Journal of Alzheimer's Disease - Volume 97, issue 4

Authors: Wheeler, Koral V. | Irimia, Andrei | Braskie, Meredith N.

Article Type: Review Article

Abstract: Cerebral amyloid angiopathy (CAA) is characterized by amyloid-β aggregation in the media and adventitia of the leptomeningeal and cortical blood vessels. CAA is one of the strongest vascular contributors to Alzheimer’s disease (AD). It frequently co-occurs in AD patients, but the relationship between CAA and AD is incompletely understood. CAA may drive AD risk through damage to the neurovascular unit and accelerate parenchymal amyloid and tau deposition. Conversely, early AD may also drive CAA through cerebrovascular remodeling that impairs blood vessels from clearing amyloid-β. Sole reliance on autopsy examination to study CAA limits researchers’ ability to investigate CAA’s natural disease …course and the effect of CAA on cognitive decline. Neuroimaging allows for in vivo assessment of brain function and structure and can be leveraged to investigate CAA staging and explore its associations with AD. In this review, we will discuss neuroimaging modalities that can be used to investigate markers associated with CAA that may impact AD vulnerability including hemorrhages and microbleeds, blood-brain barrier permeability disruption, reduced cerebral blood flow, amyloid and tau accumulation, white matter tract disruption, reduced cerebrovascular reactivity, and lowered brain glucose metabolism. We present possible areas for research inquiry to advance biomarker discovery and improve diagnostics. Show more

Keywords: Alzheimer’s disease, amyloid, cerebral amyloid angiopathy, microbleeds, neuroimaging, tau, vascular dysfunction

DOI: 10.3233/JAD-230553

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1479-1502, 2024

Authors: Wei, Guoliang | Tian, Xuelong | Yang, Hong | Luo, Yinpei | Liu, Guisong | Sun, Shuqing | Wang, Xing | Wen, Huizhong

Article Type: Review Article

Abstract: The auditory afferent pathway as a clinical marker of Alzheimer’s disease (AD) has sparked interest in investigating the relationship between age-related hearing loss (ARHL) and AD. Given the earlier onset of ARHL compared to cognitive impairment caused by AD, there is a growing emphasis on early diagnosis and intervention to postpone or prevent the progression from ARHL to AD. In this context, auditory evoked potentials (AEPs) have emerged as a widely used objective auditory electrophysiological technique for both the clinical diagnosis and animal experimentation in ARHL due to their non-invasive and repeatable nature. This review focuses on the application of …AEPs in AD detection and the auditory nerve system corresponding to different latencies of AEPs. Our objective was to establish AEPs as a systematic and non-invasive adjunct method for enhancing the diagnostic accuracy of AD. The success of AEPs in the early detection and prediction of AD in research settings underscores the need for further clinical application and study. Show more

Keywords: Age-related hearing loss, Alzheimer’s disease, auditory evoked potentials, auditory nerve system

DOI: 10.3233/JAD-230822

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1503-1517, 2024

Authors: Cui, Xiaoyan | Wang, Junqiao | Wu, Bei | Zhao, Qianhua | Tang, Xueting | Wang, Jing

Article Type: Review Article

Abstract: Background: Dementia occurring before age 65 is known as young-onset dementia (YOD), with Alzheimer’s disease being the most common type. YOD poses unique challenges for persons and families, impacting their working-age years and family responsibilities. Person-centered interventions and services are essential to improve their quality of life and social engagement. Objective: This study aims to synthesize non-pharmacological interventions for persons with YOD and their families to inform future targeted interventions. Methods: We conducted a systematic literature search across four databases: PubMed, PsycINFO, Scopus, and CINAHL. The included articles were carefully screened, categorized, and …synthesized by following Arksey and O’Malley’s five stages framework. Results: We included 20 studies reported in 24 papers, with 11 studies (14 papers) on persons with YOD and nine studies (10 papers) on families. Quantitative intervention results vary, but qualitative interviews show positive feedback. Stakeholders provided positive evaluations, stating these interventions provided a sense of normalcy, facilitated communication among families, enhanced the independence of persons with YOD, and improved the families’ caregiving self-efficacy, thereby reducing care burden and psychological distress. The heterogeneity among the studies posed integration challenges. Conclusions: Interventions for YOD can improve the quality of life for both persons with YOD and their families. More extensive intervention studies are urgently needed, especially in developing countries, with a focus on family-centered and life course perspectives. In future intervention research design, a more extensive incorporation of stakeholder involvement is essential for successful implementation. Moreover, the integration of new technologies shows promise as a potential avenue for intervention advancement. Show more

Keywords: Alzheimer’s disease, early-onset dementia, non-pharmacological interventions, review, young-onset dementia

DOI: 10.3233/JAD-231006

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1519-1531, 2024

Authors: Anlacan, Veeda Michelle M. | Lanuza, Pamela Danielle T. | Sanchez, Anna Anjelica R. | Jamora, Roland Dominic G.

Article Type: Review Article

Abstract: Background: Dementia prevalence is increasing in low- and middle-income countries such as the Philippines. Objective: This study aimed to give an overview of dementia care in the Philippines and to identify gaps in terms of local epidemiology, research, financial coverage, diagnostics, pharmacotherapy, manpower, and caregiver support. Methods: This scoping review was conducted using the Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines extension for scoping reviews. Six international and two local databases, and government and non-government websites were searched. Data published in the English or Filipino language on dementia epidemiology, research, diagnostics, …management, manpower, and training were extracted from the earliest indexed record until June 2022. Results: The prevalence of dementia in the Philippines is high and research output on all aspects of dementia is low. Cost is a major barrier as health care coverage is limited, with reliance mainly on out-of-pocket payments, leading to challenges in the proper diagnosis and treatment of dementia. There is a low specialist-to-population ratio, with shortages beyond manpower and training. Conclusions: Gaps in dementia care include limited published local data, high healthcare costs, inadequate health financing, and limited manpower. Show more

Keywords: Alzheimer’s disease, dementia, health status, practice gaps

DOI: 10.3233/JAD-230845

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1533-1543, 2024

Authors: Chang, Haiqing | Chen, Erya | Zhu, Tao | Liu, Jin | Chen, Chan

Article Type: Review Article

Abstract: Coronary artery disease is a prevalent ischemic disease that results in insufficient blood supply to the heart muscle due to narrowing or occlusion of the coronary arteries. Various reperfusion strategies, including pharmacological thrombolysis and percutaneous coronary intervention, have been developed to enhance blood flow restoration. However, these interventions can lead to myocardial ischemia/reperfusion injury (MI/RI), which can cause unpredictable complications. Recent research has highlighted a compelling association between MI/RI and cognitive function, revealing pathophysiological mechanisms that may explain altered brain cognition. Manifestations in the brain following MI/RI exhibit pathological features resembling those observed in Alzheimer’s disease (AD), implying a potential …link between MI/RI and the development of AD. The pro-inflammatory state following MI/RI may induce neuroinflammation via systemic inflammation, while impaired cardiac function can result in cerebral under-perfusion. This review delves into the role of extracellular vesicles in transporting deleterious substances from the heart to the brain during conditions of MI/RI, potentially contributing to impaired cognition. Addressing the cognitive consequence of MI/RI, the review also emphasizes potential neuroprotective interventions and pharmacological treatments within the MI/RI model. In conclusion, the review underscores the significant impact of MI/RI on cognitive function, summarizes potential mechanisms of cardio-cerebral communication in the context of MI/RI, and offers ideas and insights for the prevention and treatment of cognitive dysfunction following MI/RI. Show more

Keywords: Alzheimer’s disease, cognitive function, coronary artery disease, extracellular vesicles, myocardial ischemia/reperfusion injury, neuroinflammation, neuroprotective interventions

DOI: 10.3233/JAD-230886

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1545-1570, 2024

Authors: Armstrong, Melissa J. | Barnes, Lisa L.

Article Type: Review Article

Abstract: Dementia with Lewy bodies (DLB) is one of the most common degenerative dementias after Alzheimer’s disease (AD) dementia. DLB is under-diagnosed across populations but may be particularly missed in older Black adults. The object of this review was to examine key features of DLB and potential associations with race in order to hypothesize why DLB may be under-diagnosed in Black adults in the U.S. In terms of dementia, symptoms associated with high rates of co-pathology (e.g., AD, vascular disease) in older Black adults may obscure the clinical picture that might suggest Lewy body pathology. Research also suggests that clinicians may …be predisposed to give AD dementia diagnoses to Black adults, potentially missing contributions of Lewy body pathology. Hallucinations in Black adults may be misattributed to AD or primary psychiatric disease rather than Lewy body pathology. Research on the prevalence of REM sleep behavior in diverse populations is lacking, but REM sleep behavior disorder could be under-diagnosed in Black adults due to sleep patterns or reporting by caregivers who are not bed partners. Recognition of parkinsonism could be reduced in Black adults due to clinician biases, cultural effects on self-report, and potentially underlying differences in the frequency of parkinsonism. These considerations are superimposed on structural and systemic contributions to health (e.g., socioeconomic status, education, structural racism) and individual-level social exposures (e.g., social interactions, discrimination). Improving DLB recognition in Black adults will require research to investigate reasons for diagnostic disparities and education to increase identification of core symptoms in this population. Show more

Keywords: Alzheimer’s disease, Black or African American, dementia, Lewy body disease, parkinsonian disorders, race factors, racial groups, social determinants of health

DOI: 10.3233/JAD-231177

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1571-1580, 2024

Authors: Finch, Caleb E. | Burstein, Stanley M.

Article Type: Review Article

Abstract: Background: The possibility that Alzheimer’s disease and related dementias (ADRD) is a modern disease arises from the minimal mention of advanced cognitive decline by ancient Greeks and Romans, who were mainly concerned with the physical frailties of older ages. Objective: Because standard medical histories of elderly health lacked mention of cognitive decline, we examined texts by Greek and Roman authors that mentioned memory loss and dementia. Methods: Primary texts of Greco-Roman authors, 8th century BCE into the 3rd century CE, that mentioned cognitive decline were identified and critically evaluated. Secondary sources were excluded. …Results: No ancient account of cognitive loss is equivalent to modern clinical data. The term dementia was occasionally used in antiquity, but not invariably linked to old age. Ancient Greeks and Romans expected intellectual competence beyond age 60. While some memory loss was acknowledged, we found only four accounts of severe cognitive loss that might represent ADRD. The possibility of modest ADRD prevalence in ancient Greece and Rome is consistent with its low prevalence in the Tsimane of Bolivia. These contemporary Amerindians live under conditions of high mortality from frequent infections and minimal cardiovascular disease with physically demanding lives. Tsimane after age 60 had increased mild cognitive impairment; the few cases of dementia were not clinically consistent with AD. Conclusions: The modern ‘epidemic level’ of advanced dementias was not described among ancient Greco-Roman elderly. The possible emergence of advanced ADRD in the Roman era may be associated with environmental factors of air pollution and increased exposure to lead. Further historical analysis may formulate critical hypotheses about the modernity of high ADRD prevalence. Show more

Keywords: Aging, Alzheimer’s disease, dementia, lead, memory

DOI: 10.3233/JAD-230993

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1581-1588, 2024

Authors: Li, Jianhong | Yang, Minguang | Wei, Renli | Cao, Yue | Fan, Xu | Zhang, Shenghang

Article Type: Systematic Review

Abstract: Background: Alzheimer’s disease (AD) is a neurodegenerative disease with insidious onset. Identifying candidate predictors to forecast AD dementia risk before disease onset is crucial for early diagnosis and treatment. Objective: We aimed to assess the predictive ability of blood neurofilament light (NfL) chain in anticipating cognitive decline in the AD continuum. Methods: We systematically searched PubMed, Web of Science, and Embase from inception until April 7, 2023. Longitudinal observational studies examining the association between baseline blood NfL and cognitive decline or clinical disease conversion were included based on inclusion/exclusion criteria. The final effect size was represented …by adjusted hazard ratios (HR) or standardized beta (s.β) coefficients with a 95% confidence interval (CI). Results: A total of 2,862 articles were identified, and 26 studies were included in this meta-analysis. The results indicated that baseline blood NfL could predict cognitive decline, with MMSE [s.β= –0.17, 95% CI (–0.26, –0.07)]; PACC [s.β= –0.09, 95% CI (–0.16, –0.03)]; ADAS-cog [s.β= 0.21, 95% CI (0.13, 0.29)]; CDR-SOB [s.β= 0.27, 95% CI (0.03, 0.50)]; Global cognitive composite [s.β= –0.05, 95% CI (–0.08, –0.01)]; Memory subdomain [s.β= –0.06, 95% CI (–0.09, –0.03)]; Language subdomain [s.β= –0.07, 95% CI (–0.10, –0.05)]; Executive function subdomain [s.β= –0.02, 95% CI (–0.03, –0.01)]; Visuospatial subdomain [s.β= –0.06, 95% CI (–0.08, –0.04)]. Additionally, baseline blood NfL could predict disease progression (conversion from CU/SCD/MCI to MCI/AD) in the AD continuum [Adjust HR = 1.32, 95% CI (1.12, 1.56)]. Conclusions: Baseline blood NfL demonstrated predictive capabilities for global cognition and its memory, language, executive function, visuospatial subdomains decline in the AD continuum. Moreover, it exhibited the potential to predict disease progression in non-AD dementia participants. Show more

Keywords: Alzheimer’s disease, biomarkers, blood neurofilament light chain, cognitive decline, disease conversion

DOI: 10.3233/JAD-231080

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1589-1620, 2024

Authors: Caban-Holt, Allison | Cuccaro, Michael L. | Lloyd, Shawnta L. | Starks, Takiyah D. | Adams, Larry D. | Ford, Tayla | Haines, Jonathan L. | Beecham, Gary | Reitz, Christiane | Vance, Jeffery M. | Pericak-Vance, Margaret A. | Byrd, Goldie S.

Article Type: Short Communication

Abstract: The objective of this study was to investigate attitudes toward brain donation and perceptions of medical research that influence brain donation among African Americans. Cross-sectional surveys were administered to African American community members (n  = 227). Findings indicate that only 27% of respondents were willing to donate their brain. As medical mistrust was not found to be a significant barrier to research participation, there may be opportunity to increase brain donation by providing information about Alzheimer’s disease and brain donation to potential donors and their families so that informed decisions about participating in research can be made.

Keywords: Alzheimer’s disease, Black or African American, brain donation, dementia, medical mistrust, recruitment, research participation

DOI: 10.3233/JAD-230461

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1621-1627, 2024

Authors: Valencia-Olvera, Ana C. | Balu, Deebika | Moore, Annabelle | Shah, Maitri | Ainis, Rebecca | Xiang, Bingtao | Saleh, Yaseen | Cai, Dongming | LaDu, Mary Jo | Tai, Leon M.

Article Type: Short Communication

Abstract: APOE2 lowers Alzheimer’s disease (AD) risk; unfortunately, the mechanism remains poorly understood and the use of mice models is problematic as APOE2 homozygosity is associated with hyperlipidemia. In this study, we developed mice that are heterozygous for APOE2 and APOE3 or APOE4 and overexpress amyloid-β peptide (Aβ) (EFAD) to evaluate the effect of APOE2 dosage on Aβ pathology. We found that heterozygous mice do not exhibit hyperlipidemia. Hippocampal but not cortical levels of soluble Aβ42 followed the order E2/2FAD > E2/3FAD≤E3/3FAD and E2/2FAD > E2/4FAD < E4/4FAD without an effect on insoluble Aβ42 . These findings offer initial insights …on the impact of APOE2 on Aβ pathology. Show more

Keywords: Aβ42, Alzheimer’s disease, APOE2, hyperlipidemia, plasma lipoproteins

DOI: 10.3233/JAD-231210

Citation: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1629-1639, 2024