Infections May Help Fuel Frailty, With a Potential Push From Obesity

Infections were linked to a significantly greater risk of frailty in older people, and obesity may help shape that relationship, according to an observational cohort study.

Among 1,399 participants in the Baltimore Longitudinal Study of Aging (BLSA), having a history of infection was significantly associated with having a higher Frailty Index (FI) score (beta 0.30, P<0.001), reported Luigi Ferrucci, MD, PhD, of the National Institute on Aging in Baltimore, and colleagues.

FI progression wasn’t significantly associated with infection history across the entire population, but participants over 65 with a history of infection were more likely to progress to worse frailty levels than those without a history (HR 1.43, 95% CI 1.08-1.90, P=0.02), findings in the Journals of Gerontology: Series A showed.

“Our study found that participants with a previous history of infections had higher burden of frailty,” Ferrucci and colleagues wrote. “These results suggest that infections could accelerate a process of molecular or immunological impairment that clinically emerges as a faster decline towards the development of frailty.”

Earlier research implicates frailty as a potential driver of infections. This study flips the direction of that relationship.

“It’s getting at some of the new directions frailty research is going,” Sandra Shi, MD, MPH, a geriatrician and researcher at the Marcus Institute for Aging Research in Boston, told MedPage Today. “Why is somebody frail, and what’s driving that? This is one of the first studies to examine infections as possibly a cause of frailty.”

The current findings on infections could help clinicians in conversations with patients about the need to not skip preventive measures such as vaccinations.

The study suggests that even relatively brief infections “may leave immune fingerprints that are impacting the body’s ability to respond to stress later down the line,” Shi said. So, the message that getting the flu three or four times could increase the risk of developing frailty and aging faster “is a message I could see really sticking with patients,” she said.

Inflammation and adiposity biomarkers appeared to help shape the relationship between infections and frailty, said Ferrucci and co-authors.

FI was significantly associated with C-reactive protein in the whole study population (P<0.01) but not in those older than 65. Infection history had a significant link to higher leptin levels in the whole group (P=0.05) and the older group (P=0.005).

Leptin and obesity had a significant, positive indirect effect on the relationship between infection history and FI. Leptin mediated 2.6% of the association between infection and FI in the whole study population, rising to 4.6% in those 65 or older. Body mass index (BMI) mediated 4% of the link between infection and FI in the study’s overall population, increasing to 5.9% in the older group.

The researchers analyzed data from the ongoing BLSA, an observational cohort study measuring physical and cognitive changes among community-dwelling participants during regular follow-up visits. The current study included participants who had complete data on frailty, BMI, race, and key biomarkers. The researchers assessed participants’ history of 20 types of infection and gauged frailty using a 44-item FI of activities of daily living, mental health, and common age-related conditions.

Among participants, 64.5% had a history of any infections. Participants’ mean age was 65 years, 51.5% were women, 68.2% were white, and 24.7% were Black. Those with a history of infections were significantly older (67.1 vs 61.9 years) and had significantly greater BMI (27.4 vs 26.4) and leptin levels (2.59 vs 2.4 ng/mL).

Higher FI was observed in those with a history of pneumonia (beta 0.14, P=0.03), urinary tract infections (beta 0.15, P<0.001), herpes virus infections (beta 0.15, P=0.042), and miscellaneous viral infections (beta 0.29, P=0.001). In participants 65 years or older, a higher FI was significantly linked with urinary tract infections (beta 0.17, P=0.003), herpes virus infections (beta 0.20, P=0.009), and pneumonia (beta 0.24, P=0.001). There were no significant associations with FI for other specific infection types.

Compared with participants who had low FI and no infection history, those who had prefrail or frail FI but no infection history had a significantly increased risk of death (HR 1.81, 95% CI 1.09-3.00, P=0.02), as did those with greater FI and a history of infection (HR 1.12, 95% CI 1.05-2.10, P=0.02). Having a history of infection without frailty didn’t significantly boost mortality risk.

Study limitations included the lack of infection severity or length data. The reliance on patient self-reports and medical records to assess infections may have led to missed infection history. The use of a threshold-based frailty-progression definition may overly simplify frailty changes’ continuous progression. In addition, the BLSA participants are healthier than the general population, potentially limiting the generalizability of the study findings.