Journal of Alzheimer's Disease - Volume 91, issue 1

Authors: Golzari-Sorkheh, Mahdieh | Weaver, Donald F. | Reed, Mark A.

Article Type: Review Article

Abstract: Severe acute respiratory disease coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although a primarily respiratory disease, recent reports indicate that it also affects the central nervous system (CNS). Over 25% of COVID-19 patients report neurological symptoms such as memory loss, anosmia, hyposmia, confusion, and headaches. The neurological outcomes may be a result of viral entry into the CNS and/or resulting neuroinflammation, both of which underlie an elevated risk for Alzheimer’s disease (AD). Herein, we ask: Is COVID-19 a risk factor for AD? To answer, we identify the literature and review mechanisms by which COVID-19-mediated neuroinflammation …can contribute to the development of AD, evaluate the effects of acute versus chronic phases of infection, and lastly, discuss potential therapeutics to address the rising rates of COVID-19 neurological sequelae. Show more

Keywords: Alzheimer’s disease, COVID-19, dementia, long COVID, neuroinflammation

DOI: 10.3233/JAD-220800

Citation: Journal of Alzheimer's Disease, vol. 91, no. 1, pp. 1-23, 2023

Authors: Carcavilla-González, Nuria | Torres-Castro, Sara | Álvarez-Cisneros, Teresa | García-Meilán, Juan José

Article Type: Review Article

Abstract: The acceptance and ethics behind therapeutic lying (TL) as a non-pharmacological intervention for behavioral and psychological symptoms of dementia (BPSD) among persons with dementia continues to generate heated debates. This article presents a discussion of the ethical and cultural challenges on the perception of TL by people with dementia, their families, and health care professionals. Additionally, decision-making before TL was analyzed, including the types of TL, its efficacy and implications, alternatives to TL, and the ethical principles behind it. The results from this analysis show that TL is a common practice for BPSD. Its benefits include the reduction of these …symptoms as well as the use of physical or chemical restraints. However, there is no consensus on its suitability as an approach, nor on the appropriate way it should be used. More experimental studies are needed to create legal and clinical intervention protocols that respect the fundamental rights of people with dementia promoting coherence, good ethical practices, and guidelines for person-centered care. Show more

Keywords: Behavioral expressions, dementia, ethics, non-pharmacological, person-centered care, therapeutic lying

DOI: 10.3233/JAD-220456

Citation: Journal of Alzheimer's Disease, vol. 91, no. 1, pp. 25-31, 2023

Authors: Liu, Ziyu | Zhang, Haotian | Liu, Shiji | Hou, Yi | Chi, Guangfan

Article Type: Review Article

Abstract: Millions of patients worldwide are affected by Alzheimer’s disease (AD), and the number of patients with AD is increasing. However, current treatment can only improve symptoms but cannot cure the disease. Astrocytes, glial cells in the central nervous system, play important roles in support, nutrition, protection, and information transmission in the nervous system. Pathological changes in astrocytes are closely associated with the development and progression of AD. As carriers for material and information exchange between astrocytes and other neural cells, astrocyte-derived exosomes (ADEs) have been widely studied in recent years, and ADE secretion has been shown to be increased in …patients with AD and animal models of AD. ADEs contain a variety of substances, including nucleic acids, proteins, and lipids. The contents of ADEs can effectively control oxidative stress and detoxification during the early development of AD, thereby playing positive and negative roles in the occurrence and development of AD. In this review, we elaborate on the functions of ADEs and their components in AD and discuss their applications in AD research and clinical practice. Show more

Keywords: Alzheimer’s disease, astrocyte, exosome, neuroinflammation, neuroprotection, neurotoxicity

DOI: 10.3233/JAD-220698

Citation: Journal of Alzheimer's Disease, vol. 91, no. 1, pp. 33-42, 2023

Authors: Grobler, Corlia | van Tongeren, Marvi | Gettemans, Jan | Kell, Douglas B. | Pretorius, Etheresia

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder affecting 50 million people globally. It is characterized by the presence of extracellular senile plaques and intracellular neurofibrillary tangles, consisting of amyloid-β and hyperphosphorylated tau proteins, respectively. Despite global research efforts, there is currently no cure available, due in part to an incomplete understanding of the disease pathogenesis. Numerous possible mechanisms, or hypotheses, explaining the origins of sporadic or late-onset AD have been proposed, including the amyloid-β, inflammatory, vascular, and infectious hypotheses. However, despite ample evidence, the failure of multiple trial drugs at the clinical stage illuminates the possible pitfalls of these …hypotheses. Systems biology is a strategy which aims to elucidate the interactions between parts of a whole. Using this approach, the current paper shows how the four previously mentioned hypotheses of AD pathogenesis can be intricately connected. This approach allows for seemingly contradictory evidence to be unified in a system-focused explanation of sporadic AD development. Within this view, it is seen that infectious agents, such as P. gingivalis , may play a central role. The data presented here shows that when present, P. gingivalis or its virulence factors, such as gingipains, may induce or exacerbate pathologies underlying sporadic AD. This evidence supports the view that infectious agents, and specifically P. gingivalis , may be suitable treatment targets in AD. Show more

Keywords: Alzheimer’s disease, infectious agents, systemic inflammation, systems biology

DOI: 10.3233/JAD-220720

Citation: Journal of Alzheimer's Disease, vol. 91, no. 1, pp. 43-70, 2023

Authors: Khezri, Mohammad Rafi | Ghasemnejad-Berenji, Morteza

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide. Although the main cause of the onset and development of AD is not known yet, neuronal death due to pathologic changes such as amyloid-β (Aβ) deposition, tau aggregation, neuroinflammation, oxidative stress, and calcium dyshomeostasis are considered to be the main cause. At the present, there is no cure for this insidious disorder. However, accurate identification of molecular changes in AD can help provide new therapeutic goals. Caspases are a group of proteases which are known because of their role in cellular apoptosis. In addition, different caspases are involved in other …cellular responses to the environment, such as induction of inflammation. Emerging evidence suggest that these proteases play a central role in AD pathophysiology due to their role in the processing of amyloid-β protein precursor, tau cleavage, and neuroinflammation. Therefore, it seems that targeting caspases may be a suitable therapeutic option to slow the progression of AD. This review focuses on the role of caspases in AD pathophysiology and introduce results from studies targeted caspases in different models of AD. Show more

Keywords: Alzheimer’s disease, caspase, neurodegeneration

DOI: 10.3233/JAD-220873

Citation: Journal of Alzheimer's Disease, vol. 91, no. 1, pp. 71-90, 2023

Authors: Kyaw, Kay T. | Levine, Alec | Zhao, Amanda Jin

Article Type: Systematic Review

Abstract: Background: Establishing preventive measures to improve cognitive health of the growing older adult population is a public health priority. Though, the links between low-cost non-pharmacologist interventions that target activities like hobbies and cognitive health remain unclear. Objective: We conducted a topical review of extant literature to characterize prior findings in context and identify potential research opportunities. Methods: Search criteria was conducted with search terms “Hobbies and Dementia”, “Hobbies and Cognitive Health,” “Leisure Activities and Dementia,” and “Leisure Activities and Cognitive Health”. From the initial 383 articles, 25 articles were selected for review by using broad inclusion …and exclusion criteria. Results: Of the 25 articles included in this review, 19 were longitudinal cohort, 1 was a retrospective cohort, 2 were case–control, and 3 were cross-sectional. These studies classified hobbies as leisure activities that were cognitive/intellectual, cultural, religious, social, gardening, traveling, or physical. These studies were conducted in the United States (9), United Kingdom (3), Sweden (3), France (5), Finland (1), Korea (1), Japan (2), and China (1). The associations of different types of hobbies with dementia from these studies were not consistent. Inconsistencies could be due to limitations of study design, lack of standardized methods, sample diversity, and differences in factors like social/cultural environment across the study populations. Conclusion: This review examined existing evidence for the association between engagement in different types of hobbies and dementia and identified key knowledge gaps and promising approaches for future research. Show more

Keywords: Aging, cognitive dysfunction, dementia, hobbies

DOI: 10.3233/JAD-220593

Citation: Journal of Alzheimer's Disease, vol. 91, no. 1, pp. 91-103, 2023

Authors: Wammes, Joost D. | Swait, Joffre D. | de Bekker-Grob, Esther W. | Monin, Joan K. | Labrie, Nanon H.M. | MacNeil Vroomen, Janet L.

Article Type: Systematic Review

Abstract: Background: Discrete choice experiments (DCEs) may facilitate persons with dementia and informal caregivers to state care preferences. DCEs can be cognitively challenging for persons with dementia. Objective: This study aims to design a dementia friendly dyadic DCE that enables persons with dementia and informal caregivers to provide input individually and jointly, by testing the number of attributes and choice tasks persons with dementia can complete and providing insight in their DCE decision-making process. Methods: This study included three DCE rounds: 1) persons with dementia, 2) informal caregivers, and 3) persons with dementia and informal caregivers together. …A flexible DCE design was employed, with increasing choice task complexity to explore cognitive limitations in decision-making. Summary statistics and bivariate comparisons were calculated. A qualitative think-aloud approach was used to gain insight in the DCE decision-making processes. Transcripts were analyzed using thematic analysis. Results: Fifteen person with dementia, 15 informal caregiver, and 14 dyadic DCEs were conducted. In the individual DCE, persons with dementia completed six choice tasks (median), and 80% could complete a choice task with least three attributes. In the dyadic DCE persons with dementia completed eight choice tasks (median) and could handle slightly more attributes. Qualitative results included themes of core components in DCE decision-making such as: understanding the choice task, attribute and level perception, option attractiveness evaluation, decision rule selection, and preference adaptation. Conclusion: Persons with dementia can use simple DCE designs. The dyadic DCE was promising for dyads to identify overlapping and discrepant care preferences while reaching consensus. Show more

Keywords: Care preferences, dementia, health services, informal caregivers, Think aloud study

DOI: 10.3233/JAD-220604

Citation: Journal of Alzheimer's Disease, vol. 91, no. 1, pp. 105-114, 2023

Authors: Kenne Malaha, Angeladine | Thébaut, Clémence | Achille, Dayna | Preux, Pierre-Marie | Guerchet, Maëlenn

Article Type: Systematic Review

Abstract: Background: The proportion of people living with dementia in low- and middle-income countries (LMICs) is expected to reach 71% by 2050. Appraising the economic burden of the disease may contribute to strategic policy planning. Objective: To review studies conducted on the costs of dementia in LMICs, describe their methodology and summarize available costs estimates. Methods: Systematic review, including a search of health, economics, and social science bibliographic databases. No date or language restrictions were applied. All studies with a direct measure of the costs of dementia care were included. Results: Of the 6,843 publications …reviewed, 17 studies from 11 LMICs were included. Costs of dementia tended to increase with the severity of the disease. Medical costs were greater in the mild stage, while social and informal care costs were highest in the moderate and severe stages. Annual cost estimates per patient ranged from PPP$131.0 to PPP$31,188.8 for medical costs; from PPP$16.1 to PPP$10,581.7 for social care services and from PPP$140.0 to PPP$25,798 for informal care. Overall, dementia care can cost from PPP$479.0 to PPP$66,143.6 per year for a single patient. Conclusion: Few studies have been conducted on the costs of dementia in LMICs, and none so far in Africa. There seems to be a need to provide accurate data on the burden of disease in these countries to guide public health policies in the coming decades. Show more

Keywords: Alzheimer’s disease, cost of illness, dementia, disease burden, low-income, middle-income, systematic review

DOI: 10.3233/JAD-220239

Citation: Journal of Alzheimer's Disease, vol. 91, no. 1, pp. 115-128, 2023

Authors: Liu, Sixin | Dashper, Stuart G. | Zhao, Rui

Article Type: Systematic Review

Abstract: Background: Pre-clinical evidence implicates oral bacteria in the pathogenesis of Alzheimer’s disease (AD), while clinical studies show diverse results. Objective: To comprehensively assess the association between oral bacteria and AD with clinical evidence. Methods: Studies investigating the association between oral bacteria and AD were identified through a systematic search of six databases PubMed, Embase, Cochrane Central Library, Scopus, ScienceDirect, and Web of Science. Methodological quality ratings of the included studies were performed. A best evidence synthesis was employed to integrate the results. When applicable, a meta-analysis was conducted using a random-effect model. Results: Of …the 16 studies included, ten investigated periodontal pathobionts and six were microbiome-wide association studies. Samples from the brain, serum, and oral cavity were tested. We found over a ten-fold and six-fold increased risk of AD when there were oral bacteria (OR = 10.68 95% CI: 4.48–25.43; p  < 0.00001, I2  = 0%) and Porphyromonas gingivalis (OR = 6.84 95% CI: 2.70–17.31; p  < 0.0001, I2  = 0%) respectively in the brain. While AD patients exhibited lower alpha diversity of oral microbiota than healthy controls, the findings of bacterial communities were inconsistent among studies. The best evidence synthesis suggested a moderate level of evidence for an overall association between oral bacteria and AD and for oral bacteria being a risk factor for AD. Conclusion: Current evidence moderately supports the association between oral bacteria and AD, while the association was strong when oral bacteria were detectable in the brain. Further evidence is needed to clarify the interrelationship between both individual species and bacterial communities and the development of AD. Show more

Keywords: Alzheimer’s disease, cognitive impairment, dementia, microbiota, periodontitis, Porphyromonas gingivalis

DOI: 10.3233/JAD-220627

Citation: Journal of Alzheimer's Disease, vol. 91, no. 1, pp. 129-150, 2023

Authors: Garcia, Maria João | Leadley, Regina | Lang, Shona | Ross, Janine | Vinand, Elizabeth | Ballard, Clive | Gsteiger, Sandro

Article Type: Systematic Review

Abstract: Background: Alzheimer’s disease (AD) is the most common type of dementia, causing progressive decline of memory, thinking, and behavior, impairing daily functioning. Early AD (eAD) includes mild cognitive impairment (MCI) due to AD and mild AD dementia. Objective: The aim of this study was to investigate symptomatic treatment prevalence and treatment patterns in eAD. Methods: Embase, MEDLINE, and EBM Reviews were searched in November 2021 for observational studies reporting symptomatic treatment patterns in eAD. The range of patients receiving treatment was collated. Risk of bias was assessed using the Joanna Briggs Institute (JBI) prevalence tool. Two …independent reviewers screened the records, one performed data extraction and quality assessment while a second checked. Results: Twenty-one studies (prospective and retrospective cohorts, cross-sectional studies, and a survey) were included. Population size ranged from 23 to 2,028. Worldwide, 18 to 35% of patients diagnosed with MCI due to AD received any AChE inhibitor (three studies; n  = 631), 7 to 8% memantine (two studies; n  = 229), and 9% combination therapy (one study; n  = 402). Patients receiving no treatment ranged from 41 to 54% (two studies; n  = 733). Worldwide, in mild AD dementia patients, 13 to 89% received any AChE inhibitor (six studies; n  = 3,715), 1 to 21% memantine (five studies, n  = 3,527), and 0.4 to 39% combination therapy (four studies, n  = 3,018). Patients receiving no treatment ranged from 9 to 26% (five studies, n  = 4,073). Conclusion: Limitations in reporting led to unclear risk of bias. The results reveal a pattern of use of symptomatic treatment in eAD beyond approved labels and highlights the opportunity for new consensus guidelines to inform clinical practice. Show more

Keywords: CRD42022296104., Alzheimer’s disease, cognitive dysfunction, epidemiology, practice patterns, physicians, prodromal symptoms

DOI: 10.3233/JAD-220471

Citation: Journal of Alzheimer's Disease, vol. 91, no. 1, pp. 151-167, 2023