Geriatric Update July 1, 2024

Liraglutide 1.8 mg is the first available generic glucagon-like peptide-1 agonists (GLP-1).

To preserve bone health and achieve the most weight loss with a GLP-1 drug, combine with moderate- to vigorous-intensity exercise, in a secondary analysis of a randomized clinical trial of 195 adults aged 18 to 65 years with obesity.

New use of GLP-1 drug was significantly associated with a lower risk of Parkinson’s disease compared to new use of DPP-4 drug in 89,074 Medicare older adults with type 2 diabetes (2.85 cases per 1000 person-years) vs. DPP-4 users (3.92 cases per 1000 person-years), (HR, 0.77; 95%CI, 0.63-0.95). 

GLP-1 meds also improve obstructive sleep apnea (OSA). In trial 1, the mean change in apnea-hypopnea index (AHI) at week 52 was −25.3 events per hour with tirzepatide and −5.3 events per hour with placebo. In trial 2, the mean change in AHI at week 52 was −29.3 events per hour with tirzepatide and −5.5 events per hour (95% CI, −9.9 to −1.2) with placebo.

This well done emulated trial, identified new users (n=12,351) of GLP-1 meds in the same month, followed them 10 years 2010-2020, until the onset of dementia, identified by ICD-10 code or dementia medications, and compared them with the users of other two second-line hypoglycemic drug classes, metformin is first line. In the intention-to-treat analysis, GLP-1 agonist initiation was associated with a reduced risk of dementia compared to sulfonylureas (hazard ratio: 0.69, 95% CI: 0.60–0.79, p < 0.0001) and DPP-4 inhibitors (HR: 0.77, 95% CI: 0.68–0.88, p < 0.0001), after adjusting for confounders. The per protocol analysis was more impressive. When only metformin users were analyzed, indicating more severe diabetes, GLP-1 reduced risk compared to sulfonylureas (HR: 0.41, 95% CI: 0.32–0.53, p < 0.0001) DPP-4 inhibitors (HR for: 0.38, 95% CI: 0.30–0.49, p < 0.0001), possibly because of less risk of hypoglycemia with sulfonylureas.  The mechanism may be because most GLP-1 agonists can cross the blood–brain barrier and activate GLP-1 receptors in the brain. This activation helps regulate various processes that affect neurodegenerative diseases, such as neuroinflammation, oxidative stress, apoptosis, and dysfunction of brain glucose metabolism, enhance hippocampal connections, cerebral glucose metabolism, and hippocampal activation.

Heat is particularly dangerous for older adults because of normal aging changes and lack of reserve. This trial compared 18 older adults >65 years to 20 young adults (18-39 years) during 3 hour exposure to dry heat at 47°C or 117°F and humid heat at 41° or 106°F. In both settings body temperature increased twice as much in older adults: In the dry setting, by 1.4 °C (0.3) vs. 0.7 °C (0.3), in the humid setting by 1.1 °C (0.3) vs. 0.6 °C (0.3). This could be contributed by higher body fat in older adults 36.7% (6.8) [23.3-47.7] vs. 28.2% in the study, but also because older adults have fewer and less efficient sweat glands. Other normal aging changes include decreased thirst, increased need for fluid intake because less anti-diuretic hormone production, apoptosis or cell death in the kidney, aging kidneys do not concentrate the urine as well and we lose more fluid in the urine as we age. In the study participants drank 3 mL/kg body mass of water every hour without difference by age, leading to a greater increase in serum creatinine in older adults, in the dry setting 0.17 mg/dL (0.14) vs. 0.06 mg/dL (0.08), and in the humid setting 0.06 mg/dL (0.01) but no change in young adults. I would like to have seen baseline hydration status of older adults in the study because kidney function as eGFR, mL/min/1.73 m2 was 84 vs. 106. Although I have many criticisms of the study, the take away is that we need to be aware of heat risk to our older adults and make sure they drink enough.

This large cohort study evaluated the rate of incident stroke and vascular dementia in 36,340 patients with atrial fibrillation (AF) and a low apparent risk of stroke, defined as a CHA2DS2-VASc score of 0 or 1 and not usually necessitating anticoagulation. Incident stroke occurred in 1,366 (3.8%) patients with AF compared to 1,796 (1.5%) in the matched control group over 5 years follow up, arterial thromboembolism 0.3% vs. 0.1% (HR 2.39, 95% CI 1.83–3.11; P < 0.001), and all-cause mortality 8.9% versus 5.0% (HR 1.44, 95% CI 1.38–1.50; P < 0.001), ischemic heart disease in 1,870 (5.6%) vs. 3,030 (2.7%) HR 1.88 (95% CI 1.77–1.99; P < 0.001), and vascular dementia in 126 (1.2%) vs. 162 (0.7%) (HR 1.68, 95% CI 1.33–2.12; P < 0.001). We should discuss this increased risk with our patients for informed decision making.

Adults who reside in senior housing are less likely to be ill or have accidents, although more vulnerable before moving, vulnerability levels off and declines shortly after moving in, are more likely to receive home health care, less likely to be hospitalized from an emergency department. They have Increased Longevity, live more than one week longer and have a lower mortality rate than older adults who live in the community.

In 94,090 percutaneous coronary intervention (PCI)-treated STEMI patients with high use of guideline-recommended therapy, mortality within 30 days of ST-segment elevation myocardial infarction (STEMI) is much higher than the general population, and 31-90 days is still double, but patients surviving the first 90 days had 10-year mortality that was only 2% higher than that of a matched general population.