Association of Family Support With Lower Modifiable Risk Factors for Dementia Among Cognitively Impaired Older Adults.

OBJECTIVES: Cognitive impairment poses considerable challenges among older adults, with the role of family support becoming increasingly crucial. This study examines the association of children's residential proximity and spousal presence with key modifiable risk factors for dementia in cognitively impaired older adults. METHODS: We analyzed 14,600 individuals (35,165 observations) aged 50 and older with cognitive impairment from the Health and Retirement Study (1995-2018). Family support was categorized by spousal presence and children's residential proximity. Modifiable risk factors, including smoking, depressive symptoms, and social isolation, were assessed. Associations between family support and the modifiable risk factors were determined using mixed-effects logistic regressions. RESULTS: A significant proportion of older adults with cognitive impairment lacked access to family support, with either no spouse (46.9%) or all children living over 10 miles away (25.3%). Those with less available family support, characterized by distant-residing children and the absence of a spouse, had a significantly higher percentage of smoking, depressive symptoms, and social isolation. Moreover, we revealed a consistent gradient in the percentage of the risk factors by the degree of family support. Relative to older adults with a spouse and co-resident children, those without a spouse and with all children residing further than 10 miles displayed the highest percentage of the risk factors. These findings were robust to various sensitivity analyses. CONCLUSIONS: Family support from spouses and nearby children serves as a protective factor against modifiable dementia risk factors in cognitively impaired older adults. Policies that strengthen family and social support may benefit this population.

Children's Residential Proximity, Spousal Presence and Modifiable Risk Factors for Dementia among Older Adults with Cognitive Impairment.

Background: Cognitive impairment in older adults poses considerable challenges, and the role of family support becomes increasingly crucial. This study aims to examine the impact of children's residential proximity and spousal presence on the key modifiable risk factors for dementia among older adults with cognitive impairment. Methods: Utilizing the Health and Retirement Study (HRS) data from 1995 to 2018, we analyzed 14,731 participants (35,840 person-waves) aged 50 and older with cognitive impairment. Family support was characterized based on the presence of a spouse and residential proximity to children. Smoking, depressive symptoms and social isolation were included as the key modifiable risk factors for dementia identified in later life. Using mixed-effects logistic regressions, associations between access to family support and the modifiable risk factors were determined, adjusting for various socio-demographic and health-related factors. Results: Significant associations were found between access to family support and modifiable risk factors for dementia. Cognitively impaired older adults with less available family support, characterized by distant-residing children and the absence of a spouse, had significantly higher risks of smoking, depressive symptoms, and social isolation. Moreover, we revealed a consistent gradient in the prevalence of the risk factors based on the degree of family support. Relative to older adults with a spouse and co-resident children, those without a spouse and with all children residing further than 10 miles displayed the highest risks of smoking, depressive symptoms, and social isolation. Conclusion: Access to family support, particularly from spouses and proximate children, plays a protective role against key modifiable risk factors for dementia in older adults with cognitive impairment. The findings highlight the need for bolstering family and social support systems to enhance the well-being of this vulnerable population.

mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease.

Glycogen Storage Disease 1a (GSD1a) is a rare, inherited metabolic disorder caused by deficiency of glucose 6-phosphatase (G6Pase-α). G6Pase-α is critical for maintaining interprandial euglycemia. GSD1a patients exhibit life-threatening hypoglycemia and long-term liver complications including hepatocellular adenomas (HCAs) and carcinomas (HCCs). There is no treatment for GSD1a and the current standard-of-care for managing hypoglycemia (Glycosade®/modified cornstarch) fails to prevent HCA/HCC risk. Therapeutic modalities such as enzyme replacement therapy and gene therapy are not ideal options for patients due to challenges in drug-delivery, efficacy, and safety. To develop a new treatment for GSD1a capable of addressing both the life-threatening hypoglycemia and HCA/HCC risk, we encapsulated engineered mRNAs encoding human G6Pase-α in lipid nanoparticles. We demonstrate the efficacy and safety of our approach in a preclinical murine model that phenotypically resembles the human condition, thus presenting a potential therapy that could have a significant therapeutic impact on the treatment of GSD1a.

Self-Acceptance and Interdependence Promote Longevity: Evidence From a 20-year Prospective Cohort Study.

We explored psychosocial pathways to longevity, specifically, the association between psychological well-being and mortality in a 20-year prospective cohort study of 7626 participants. As hypothesized, high self-acceptance and interdependence were associated with decreased mortality risk, controlling for other psychological components (purpose, positive relations, growth, mastery) and potential confounders: personality, depression, self-rated health, smoking status, body mass index (BMI), illness, and demographics. Self-acceptance decreased mortality risk by 19% and added three years of life. Longevity expectation fully mediated the relationship between self-acceptance and mortality. Interdependence decreased mortality risk by 17% and added two years of life. Serenity towards death fully mediated the relationship between interdependence and mortality. This is the first known study to investigate self-acceptance, interdependence, and serenity toward death as promoters of longevity, and distilled the relative contributions of these factors, controlling for covariates-all of which were measured over multiple time points. Theoretically, this study suggests that components of well-being may make meaningful contributions to longevity, and practically recommend that self-acceptance and interdependence could be added to interventions to promote aging health.

mRNA Therapy Improves Metabolic and Behavioral Abnormalities in a Murine Model of Citrin Deficiency.

Citrin deficiency is an autosomal recessive disorder caused by loss-of-function mutations in SLC25A13, encoding the liver-specific mitochondrial aspartate/glutamate transporter. It has a broad spectrum of clinical phenotypes, including life-threatening neurological complications. Conventional protein replacement therapy is not an option for these patients because of drug delivery hurdles, and current gene therapy approaches (e.g., AAV) have been hampered by immunogenicity and genotoxicity. Although dietary approaches have shown some benefits in managing citrin deficiency, the only curative treatment option for these patients is liver transplantation, which is high-risk and associated with long-term complications because of chronic immunosuppression. To develop a new class of therapy for citrin deficiency, codon-optimized mRNA encoding human citrin (hCitrin) was encapsulated in lipid nanoparticles (LNPs). We demonstrate the efficacy of hCitrin-mRNA-LNP therapy in cultured human cells and in a murine model of citrin deficiency that resembles the human condition. Of note, intravenous (i.v.) administration of the hCitrin-mRNA resulted in a significant reduction in (1) hepatic citrulline and blood ammonia levels following oral sucrose challenge and (2) sucrose aversion, hallmarks of hCitrin deficiency. In conclusion, mRNA-LNP therapy could have a significant therapeutic effect on the treatment of citrin deficiency and other mitochondrial enzymopathies with limited treatment options.

Systemic mRNA Therapy for the Treatment of Fabry Disease: Preclinical Studies in Wild-Type Mice, Fabry Mouse Model, and Wild-Type Non-human Primates.

Fabry disease is an X-linked lysosomal storage disease caused by loss of alpha galactosidase A (α-Gal A) activity and is characterized by progressive accumulation of globotriaosylceramide and its analogs in all cells and tissues. Although enzyme replacement therapy (ERT) is considered standard of care, the long-term effects of ERT on renal and cardiac manifestations remain uncertain and thus novel therapies are desirable. We herein report preclinical studies evaluating systemic messenger RNA (mRNA) encoding human α-Gal A in wild-type (WT) mice, α-Gal A-deficient mice, and WT non-human primates (NHPs). The pharmacokinetics and distribution of h-α-Gal A mRNA encoded protein in WT mice demonstrated prolonged half-lives of α-Gal A in tissues and plasma. Single intravenous administration of h-α-Gal A mRNA to Gla-deficient mice showed dose-dependent protein activity and substrate reduction. Moreover, long duration (up to 6 weeks) of substrate reductions in tissues and plasma were observed after a single injection. Furthermore, repeat i.v. administration of h-α-Gal A mRNA showed a sustained pharmacodynamic response and efficacy in Fabry mice model. Lastly, multiple administrations to non-human primates confirmed safety and translatability. Taken together, these studies across species demonstrate preclinical proof-of-concept of systemic mRNA therapy for the treatment of Fabry disease and this approach may be useful for other lysosomal storage disorders.

Health advantages of ethnic density for African American and Mexican American elderly individuals.

Research suggests that greater ethnic density correlates with worse health among African Americans but better health among Hispanic Americans. These conflicting patterns may arise from Hispanic American samples being older than African American samples. We found that among 2367 Mexican American and 2790 African American participants older than 65 years, ethnic density predicted lower rates of cardiovascular disease and cancer, adjusting for covariates, showing that the health benefits of ethnic density apply to both minority communities.

Exclusion of elderly persons from health-risk behavior clinical trials.

BACKGROUND: It has been found that the elderly population is underrepresented in clinical trials aimed at disease treatment. It is unknown to what extent this group is also excluded from clinical trials aimed at reducing health-risk behaviors. METHOD: We systematically reviewed clinical trials targeting the leading health-risk behaviors, as identified by Healthy People 2010: tobacco use, overweight/obesity, physical inactivity, substance abuse, and irresponsible sexual behavior. Using MEDLINE, we identified clinical trials published in the five most cited medical journals between January 1990 and May 2004. RESULTS: The majority (53%) of the 198 health-risk behavior clinical trials excluded persons over the age of 65; the exclusion percentage increased to 72% for those over the age of 75. The exclusion of elderly persons in these five medical journals did not decline over the 14 years studied. This age exclusion pattern was not explained by the intervention's intrusiveness or whether illness was an exclusion criterion. The trials that included those over the age of 65 were more likely to report a significant finding in the predicted direction. CONCLUSIONS: Although elderly persons are most at risk for diseases linked to lifestyle behavior, such as heart disease, they were excluded from the majority of health-risk behavior clinical trials in five major medical journals.

Hearing decline predicted by elders' stereotypes.

Although age-related hearing loss is one of the most prevalent conditions affecting older individuals, little research has been conducted on the social-psychological factors that might contribute to it. The present study examines whether older individuals' age stereotypes predict screened hearing over time. The sample consisted of 546 community-dwelling persons, aged 70 to 96 years old. Participants with more negative and more external (i.e., related to physical appearance) age stereotypes demonstrated worse screened hearing at 36 months, after adjusting for baseline-screened hearing, age, and other relevant variables. These findings suggest that age stereotypes influence older individuals' sensory perception.

Preventive health behaviors influenced by self-perceptions of aging.

BACKGROUND: Research has found that the elderly are the age group that is the least likely to engage in preventive health behaviors, even though these behaviors continue to benefit individuals throughout the life span. We investigated for the first time whether an age-specific factor, older individuals' beliefs about their own aging, predicts their likelihood of engaging in preventive health behaviors over time. METHODS: We conducted multivariate linear regression to test the predictive value of aging self-perceptions on the preventive health behaviors of 241 individuals, who participated in the Ohio Longitudinal Study of Aging and Retirement (OLSAR) aged 50-80 years old. The preventive health behaviors included eating a balanced diet, exercising, and following directions for taking prescribed medications. RESULTS: Individuals with more positive self-perceptions of aging tended to practice more preventive health behaviors over the next two decades after controlling for age, education, functional health, gender, self-rated health, and race (P = 0.032). CONCLUSIONS: Our findings suggest that addressing views about aging could help improve efforts to increase preventive health behaviors in the older population.