Dyslipidemia and the Risk of Alzheimer’s Disease

Whether cholesterol is implicated in the pathogenesis of Alzheimer’s disease (AD) is still controversial. Several studies that explored the association between lipids and/or lipid-lowering treatment and AD indicate a harmful effect of dyslipidemia on AD risk. The findings are supported by genetic linkage and association studies that have clearly identified several genes involved in cholesterol metabolism or transport as AD susceptibility genes, including apolipoprotein E (APOE), apolipoprotein J (APOJ, CLU), ATP-binding cassette subfamily A member 7(ABCA7), and sortilin-related receptor (SORL1). Functional cell biology studies further support a critical involvement of lipid raft cholesterol in the modulation of Aβ precursor protein processing by β-secretase and γ-secretase resulting in altered Aβ production. However, conflicting evidence comes from epidemiological studies showing no or controversial association between dyslipidemia and AD risk, randomized clinical trials observing no beneficial effect of statin therapy, and cell biology studies suggesting that there is little exchange between circulating and brain cholesterol, that increased membrane cholesterol level is protective by inhibiting loss of membrane integrity through amyloid cytotoxicity, and that cellular cholesterol inhibits colocalization of β-secretase?1 and Aβ precursor protein in nonraft membrane domains, thereby increasing generation of plasmin, an Aβ-degrading enzyme. The aim of this article is to provide a comprehensive review of the findings of epidemiological, genetic, and cell biology studies aiming to elucidate the role of cholesterol in the pathogenesis of AD.     

Etiology and Pathogenesis of Late-Onset Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative condition that occurs in two forms, an early-onset form that is genetically determined and a far more common late-onset form that is not. In both cases, the disease results in severe cognitive dysfunction, among other problems, and the late-onset form of the disease is now considered to be the most common cause of dementia among the elderly. While a good deal of research has been focused on elucidating the etiology of the late-onset form for more than two decades, results to date have been modest and have not yet engendered useful therapeutic strategies for cure of the disease. In this review, we discuss the prevalent ideas that have governed this research for several years, and we challenge these ideas with alternative findings suggesting a multifactorial etiology. We review promising newer ideas that may prove effective as therapeutic interventions for late-onset AD, as well as providing reliable means of earlier and more specific diagnosis of the disease process. In the discussions included here, we reference relevant clinical and basic science literature underlying research into disease etiology and pathogenesis, and we highlight current reviews on the various topics addressed.     

Knowledge,Attitudes, and Cultural Beliefs about Healthy Aging and Alzheimer’s Disease among Older Chinese Americans in New York City

Journal of Cross-Cultural Gerontology - Alzheimer’s Disease (AD) and Related Dementias (ADRD) are a growing concern across the globe. Unfortunately, racial/ethnic minorities in the United...     

Engaging Stakeholders in the Design and Conduct of Embedded Pragmatic Clinical Trials for Alzheimer’s Disease and Alzheimer’s Disease–Related Dementias

Embedded pragmatic clinical trials (ePCTs) of nondrug interventions for Alzheimer’s disease and Alzheimer’s disease–related dementias (AD/ADRD) are conducted in real-world clinical settings and designed to generate an evidence base to inform clinical and policy decisions about care for this vulnerable population. The ePCTs exist within a complex ecosystem of relationships between researchers, payors, policymakers, healthcare systems, direct care staff, advocacy groups, families, caregivers, and people living with dementia (PLWD). Because the rapid increase of the number of Americans with AD/ADRD outpaces curative treatments, there is an urgent need to mobilize the power of these relationships to improve dementia care and address a mounting public health crisis. Stakeholder engagement in ePCTs is essential to generate research questions, establish the relevancy of trials to the intended end users, and understand the factors that influence dissemination and implementation in real-world clinical settings. The process of including stakeholders in ePCTs for dementia is similar to stakeholder engagement in ePCTs for other diseases and conditions; however, the unique nature of embedded research, prevalence of caregiver and provider burden, and the progressive worsening of cognitive impairment in PLWD must be approached with additional strategies. This article presents key considerations of stakeholder engagement for ePCTs in AD/ADRD and main activities of the stakeholder engagement team in the National Institute on Aging IMPACT Collaboratory to move the field forward. J Am Geriatr Soc 68:S62–S67, 2020 .     

Confirmatory Factor Analysis of the Quality of Life in Alzheimer’s Disease Scale in Patients with Alzheimer’s Disease

Background/Study Context: Quality of life (QoL) has become an important outcome measure in clinical trials for Alzheimer’s disease (AD). The Quality of Life in Alzheimer’s Disease (QoL-AD) Scale is widely used for assessing QoL of patients with AD. This research aims to determine the factor structure of the QoL-AD Scale in AD patients.

Methods: One hundred thirty-nine patients with mild-to-moderate AD were administered the QoL-AD Scale. Based on the model proposed for healthy people, confirmatory factor models were built using modification indices and residual analysis to improve the model fit.

Results: Confirmatory factor analysis indicated poor fit for both the initial model and the single-factor model. Two models showed a good fit: a three-factor model (perceived health, perceived environment and perceived functional ability) and a two-factor model (perceived physical health and perceived psychological health). Because no differences in fit were found between both models, the authors proposed the more parsimonious solution as the best model.

Conclusion: These results provide evidence supporting the construct validity of the QoL-AD Scale. This instrument seems to measure the perception of two related constructs (behavioral competence and environment) and could be used together with instruments measuring psychological well-being and the perception of health.     

Changes in Chemosensitivity and Mechanosensitivity in Aging and Parkinson’s Disease

The risk of aspiration pneumonia in Parkinson’s disease (PD) may be increased by sensory loss in the laryngopharynx and a reduced cough reflex. This study investigated changes in chemo- and mechanosensation with age and in PD and documented cough thresholds and cortical influences over cough. Single-breath citric acid inhalation cough challenge and flexible nasendoscopy were performed in 32 participants with idiopathic PD (mean age = 68.5 years, range = 45.8–82.5) and 16 healthy young adults (8 males, mean age = 25.1 years, range = 21.3–32.4), and 16 healthy elders (8 males, mean age = 72.8 years, range = 61.5–84.7) as controls. Individuals with PD had reduced sensation at the base of the tongue compared to age- and gender-matched counterparts (p < 0.005). All groups demonstrated lower natural cough thresholds than suppressed cough thresholds. No differences in natural cough thresholds were found across groups. Young adults demonstrated greater ability to suppress cough compared to healthy elders (p = 0.021). Tongue-base mechanosensory impairment in PD may account for vallecular residue and complaints of globus sensation. However, decreased cough response was not found to be a characteristic of PD. This study provided evidence for voluntary control of cough and the lack of decline of chemosensitivity with age or disease.     

Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrP^Sc, an aberrantly folded isoform of the cellular prion protein PrP^C, in the brains of affected individuals. PrP^C is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI) anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrP^C and prevents PrP^Sc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer’s disease (AD): whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD.     

Levels and Correlates of Knowledge about Alzheimer’s Disease among Older Chinese Americans

Objective: This study examined knowledge of Alzheimer’s disease (AD) and correlates of AD knowledge in a sample of Chinese American older adults living in the Phoenix metropolitan area of the United States. Methods: Survey data were collected from 385 Chinese Americans age 55 or older (M?=?72.43, SD?=?8.67) recruited from various settings not limited to senior housing facilities, senior clubs, senior centers and church groups. Results: Participants responded to a 24-item true/false AD knowledge scale with 73 % accuracy. Multivariate regression analyses found that participants who held more traditional Chinese cultural beliefs of AD tended to have less AD knowledge. Older women had more knowledge of AD than men when educational differences were controlled. Participants who used media to acquire AD information had more AD knowledge than those did not. Conclusions: AD educational programs should target domains (e.g., risk factors, symptoms, and caregiving) about which Chinese American elders tend to have less knowledge; AD information should be disseminated through appropriate media to outreach Chinese American elders more effectively. Addressing the biases in elders’ cultural beliefs of AD should be incorporated in AD educational programs.     

Health Service Provider’s Perspectives on Healthy Aging in India

This qualitative inquiry explored the meaning of healthy aging, health status of the elderly they serve, availability of programs and services, and knowledge of policies specific to seniors from the perspective of health service providers in India. To this end, 100 physicians, allied and alternative health care providers were recruited using snowball sampling method and interviewed in person. The health service providers showed an overall tendency toward holistic definitions including aspects of physical, mental and social wellbeing and reported widely prevalent health problems in each of those domains (e.g., physical health problems, social health concerns resulting from changing family structure). In discussing programs and services available to seniors, a wide range was evident; however the need for expanded health and social support was clear. In order to adequately respond to this need, policy development and implementation relating to the aging population is necessary and three key considerations are highlighted.     

Alzheimer’s Disease and Type 2 Diabetes: Multiple Mechanisms Contribute to Interactions

Obesity, metabolic syndrome, and type 2 diabetes (T2D) are related disorders with widespread deleterious effects throughout the body. One important target of damage is the brain. Persons with metabolic disorders are at significantly increased risk for cognitive decline and the development of vascular dementia and Alzheimer’s disease. Our review of available evidence from epidemiologic, clinical, and basic research suggests that neural dysfunction from T2D-related disease results from several underlying mechanisms, including metabolic, inflammatory, vascular, and oxidative changes. The relationships between T2D and neural dysfunction are regulated by several modifiers. We emphasize 2 such modifiers, the genetic risk factor apolipoprotein E and an age-related endocrine change, low testosterone. Both factors are independent risk factors for Alzheimer’s disease that may also cooperatively regulate pathologic interactions between T2D and dementia. Continued elucidation of the links between metabolic disorders and neural dysfunction promises to foster the development of effective therapeutic strategies.     

Efficacy of Creative Arts Therapy in Treatment of Alzheimer’s Disease and Dementia: A Systematic Literature Review

This systematic literature review identifies existing evidence regarding the effectiveness of creative arts therapies among persons with memory loss and their care providers. A total of 112 articles were analyzed. Data from each article were extracted and synthesized to identify patterns in published results. Findings suggest that creative arts therapy is effective for treatment of behavioral and emotional challenges of the disease, but not for treatment of cognitive decline. However, small sample sizes, short (or nonexistent) follow-up, and the difficulty quantifying findings remain as challenges when interpreting the efficacy of creative arts therapy for persons with memory loss.     

Multimedia Aided Consent for Alzheimer’s Disease Research

Objectives: Optimizing the research consent process simultaneously fosters respect for autonomy and protection of those with diminished capacity for autonomy. This study evaluated the effectiveness of an enhanced research consent procedure, employing multimedia disclosure and corrective feedback, in improving decisional capacity among 114 people with mild-to-moderate Alzheimer’s disease (AD) and 134 non-psychiatric comparison (NC) subjects.

Methods: Participants were randomized to consent type (routine versus enhanced) and protocol type (lower versus higher risk). Outcomes included a 5-item questionnaire assessing immediate comprehension, MacArthur Competence Assessment Tool for Clinical Research assessing four components of decision-making capacity, and categorical decisional capacity (based on a cut-score established in reference to expert judgments for a subset of participants).

Results: There was no significant effect of the enhanced consent procedure, relative to routine consent, on immediate comprehension or decisional capacity.

Conclusions: Multimedia tools do not appear to be the solution to better consent for AD research.

Clinical Implications: Given the ethical primacy of informed consent and issues of justice for impaired populations who might be harmed by an absence of research-based treatment advances, continued search for ways to more meaningfully engage people with AD in the consent or assent process is warranted.