Journal Article Annotations
2023, 1st Quarter
Annotations by Zach Harvanek, MD, PhD
In the Health and Retirement Study (HRS), the authors identified that older adults who volunteered were biologically younger (as measured by 6 of 13 epigenetic clocks) than adults who did not volunteer in the past year. Notably, this was true for 4 of 4 epigenetic clocks trained to predict future morbidity and mortality (“2nd generation clocks”). This difference in biological age was independent of current diabetes, cardiovascular disease, stroke, cancer, hypertension, and demographic factors but was heavily influenced by current health behaviors such as heavy drinking, smoking, physical activity, and body mass index.
Strength and weaknesses:
A strength of this study is its large sample size (n=4011) with a relatively diverse patient population. Consistent findings across 2nd generation clocks suggest strong internal validity—and likely a difference in future morbidity and mortality. Finally, the investigators attempted to correct for health selection bias by correcting for current disease status. Weaknesses include that the analysis is cross-sectional, and because of this, there is unclear causality: alcohol and smoking could dissuade individuals from volunteering and also lead to accelerated aging. Conversely, volunteering could reduce drinking habits and encourage physical activity, which in turn helps slow biological aging.
While the data are cross-sectional, the findings suggest that interventions such as engaging patients in volunteering may help slow biological aging. The positive effect may occur through improved health behaviors. From a psychiatric perspective, encouraging social engagement through activities such as volunteering may benefit both physical morbidity and mortality as well as psychiatric health, such as substance misuse.
In an observational study using the UK Biobank and prescription data from the UK National Health Service, the investigators identified that lithium use appeared to significantly improve survival in individuals with affective disorders compared to those taking anti-psychotics. This benefit persisted in both males and females and did not appear to be driven primarily by any specific cause of death. The authors also re-demonstrated the relatively well-known finding that those with affective disorders have shorter lifespans than healthy controls; this difference related to both suicide and natural causes. The study included mostly older adults (average age 57), over half of whom had a serious medical condition or disability.
Strength and weaknesses:
Strengths of the study include that it is a relatively large observational study (276 lithium users and 552 for anti-psychotic users). The comparison of lithium users to those on anti-psychotic medication seems appropriate, as both groups likely have more treatment-resistant mood issues than those who were treated with anti-depressants alone. The use of propensity score matching to identify controls based on sex, age, diagnosis, and comorbidities also is a strength. The lack of comparison to an untreated group of some sort is a weakness, as the current finding could also be a result of anti-psychotics reducing lifespan, instead of lithium increasing lifespan. The reliance on prescription databases is reasonable, though data suggesting patients are taking the medication (such as blood levels) would provide stronger evidence. Finally, relatively few individuals died over the course of the study (12 lithium users and 58 anti-psychotic users).
These data support the use of lithium for the treatment of affective disorders, particularly over anti-psychotics. These data would support choosing lithium when considering an adjunct medication for long-term treatment of affective disorders, including in the elderly and those with serious medical conditions.
This study found that individuals with diabetes who had been on metformin had significantly reduced risk of delirium compared to those with diabetes but not on metformin. After correction for other factors, metformin use had an odds ratio (OR) for delirium of 0.5. In sub-group analyses, metformin appeared to reduce the risk of delirium among patients with dementia (OR 0.54) but not in those without dementia (OR 0.4). Additionally, those with diabetes but not on metformin had significantly higher mortality than those with diabetes on metformin—a risk that persisted over 3 years.
Strength and weaknesses:
This is a novel, observational study which utilized multiple measures of delirium and included patients admitted to general floors, intensive care units, and the emergency department. The broad inclusion criteria enhances generalizability of the findings. Limitations of the study include the use of hospital records to determine whether patients were taking metformin prior to admission, and that other markers of diabetic control (A1C, usage of medications besides metformin or insulin) did not seem to be assessed. Sample size also seemed to limit analyses of subgroups with and without dementia.
This study suggests that those with diabetes and a known, upcoming risk for delirium (eg, upcoming surgery) may be able to decrease both their risk of delirium and also mortality by taking metformin. Whether this would be true for those with dementia is unclear, as the study’s small sample size limited inferences.