Polypharmacy, anticholinergic burden and inflammation in relation to accelerated biological ageing.

Polypharmacy and hyperpolypharmacy were highly prevalent among older US adults taking prescription medications.

• Analysis included 10,556 older adults aged 65 years or older taking at least one prescription medication from NHANES 1999-2018.
• 35.0% of participants had polypharmacy (5-9 concurrent drugs).
• 5.5% of participants had hyperpolypharmacy (≥10 concurrent drugs).
• Polypharmacy was defined by concurrent use of 5-9 drugs and hyperpolypharmacy as ≥10 drugs.

Both polypharmacy and anticholinergic burden were significantly associated with accelerated biological ageing across multiple measures.

• Associations were found with phenotypic age (PhenoAge), Klemera-Doubal biological age (KD-BioAge), anthropometric age (AnthroAge), and frailty index.
• Anticholinergic burden was assessed via the Anticholinergic Drug Scale (ADS).
• Associations were adjusted for confounders using weighted multiple linear regression.
• No significant associations were reported for telomere length or α-Klotho.

Systemic inflammation response index (SIRI) partially mediated the association between polypharmacy and PhenoAge acceleration.

• SIRI mediated 17.3%–26.9% of the association between polypharmacy/anticholinergic burden and PhenoAge acceleration (both P < .001).
• Inflammation was quantified using five blood cell-based indices.
• SIRI was identified as the key inflammatory mediator among the five indices assessed.
• The mediation was statistically significant (P < .001).

Systemic inflammation response index (SIRI) partially mediated the association between polypharmacy and KD-BioAge acceleration.

• SIRI mediated 9.8%–11.7% of the association between polypharmacy/anticholinergic burden and KD-BioAge acceleration (both P < .001).
• Mediation analyses were performed using weighted methods.
• The proportion mediated was smaller for KD-BioAge than for PhenoAge.

A serial mediation pathway from polypharmacy through anticholinergic burden (ADS) to SIRI to biological ageing was identified.

• The ADS-SIRI serial pathway mediated 3.1% of the association between polypharmacy and PhenoAge acceleration (P = .003).
• The ADS-SIRI serial pathway mediated 1.7% of the association between polypharmacy and KD-BioAge acceleration (P = .005).
• This represents a serial mediation where polypharmacy increases anticholinergic burden, which in turn increases inflammation, which then accelerates biological ageing.
• Both serial mediation effects were statistically significant.

The study used a cross-sectional design using NHANES data spanning nearly two decades.

• Data were drawn from the National Health and Nutrition Examination Survey (NHANES) 1999–2018.
• The study included US adults aged 65 years or older taking at least one prescription medication.
• Biological ageing was measured using six measures: PhenoAge, KD-BioAge, AnthroAge, frailty index, telomere length, and α-Klotho.
• The cross-sectional design limits causal inference.