Cognitive Frailty and Drug Burden in Near-Centenarians (95 Years and Older Adults)

Abstract

Cognitive Frailty and Drug Burden in Near-Centenarians (95 Years and Older Adults)

Abstract

Abstract Purpose: Cognitive frailty is an emerging concept in geriatric medicine, defined by the coexistence of cognitive impairment and physical frailty without dementia. We planned to investigate the relationship between cognitive frailty and drug burden in individuals aged 95 years and older. Material and Methods: This retrospective cross-sectional study included 193 individuals aged ≥95 years receiving care at geriatric outpatient clinics or residential facilities in Turkey. Data on cognitive status, comorbidities, and regular medication use were obtained from medical records. Cognitive frailty was identified based on documented as cooccurrence of physical frailty and cognitive impairment. Results: Among the participants, 45.1% were identified as cognitively frail. The cognitive frailty group exhibited a significantly lower mean MMSE score (19.8 ± 3.7) in comparison to the control group (24.7 ± 3.1, p < 0.001). The mean number of medications was higher among cognitive frailty participants (6.3 ± 2.1) than those without cognitive frailty (4.1 ± 1.8, p < 0.01). After adjusting for all variables, increased age (OR: 1.11, 95% CI: 1.03–1.20, p = 0.006), higher number of comorbidities (OR: 1.23, 95% CI: 1.05–1.45, p = 0.014), and greater number of medications (OR: 1.36, 95% CI: 1.14–1.64, p = 0.001) were significantly associated with increased cognitive frailty. Conclusion: Cognitive frailty is independently associated with a higher drug burden in individuals aged 95 and older. Integrating cognitive and frailty assessments into routine geriatric evaluations may help mitigate the risks of polypharmacy in this vulnerable population.

Keywords

• cognitive frailty
• polypharmacy
• older adults
• near-centenarians
• geriatric care

References

1. Katipoglu B, Kocyigit SE, Ergun U, Kocak AO, Aydeniz O, Mert I, et al. A community-based integrated healthy aging program at a tertiary hospital (YASAM) for the oldest old participants may have the potential to reduce emergency admission: Preliminary evidence from a pre–post-intervention study. The Journal of Emergency Medicine. 2025;72:112-20.
2. Katipoglu B, Kocyigit SE. Impact of geriatric syndrome burden on healthcare services utilization and mortality among community-dwelling older adults: is it still too late to do something? Eur Geriatr Med. 2025;16(3):1055-61.
3. Panza F, Solfrizzi V, Barulli MR, Santamato A, Seripa D, Pilotto A, et al. Cognitive frailty: a systematic review of epidemiological and neurobiological evidence of an age-related clinical condition. Rejuvenation research. 2015;18(5):389-412.
4. Rivan NFM, Singh DKA, Shahar S, Wen GJ, Rajab NF, Din NC, et al. Cognitive frailty is a robust predictor of falls, injuries, and disability among community-dwelling older adults. BMC geriatrics. 2021;21:1-13.
5. Bu Z, Huang A, Xue M, Li Q, Bai Y, Xu G. Cognitive frailty as a predictor of adverse outcomes among older adults: A systematic review and meta‐analysis. Brain and behavior. 2021;11(1):e01926.
6. Gutiérrez‐Valencia M, Izquierdo M, Cesari M, Casas‐Herrero Á, Inzitari M, Martínez‐Velilla N. The relationship between frailty and polypharmacy in older people: a systematic review. British journal of clinical pharmacology. 2018;84(7):1432-44.
7. Woolford SJ, Aggarwal P, Sheikh CJ, Patel HP. Frailty, multimorbidity and polypharmacy. Medicine. 2021;49(3):166-72.
8. Zazzara MB, Palmer K, Vetrano DL, Carfì A, Graziano O. Adverse drug reactions in older adults: a narrative review of the literature. Eur Geriatr Med. 2021;12:463-73.

9. Chiatti C, Bustacchini S, Furneri G, Mantovani L, Cristiani M, Misuraca C, et al. The economic burden of inappropriate drug prescribing, lack of adherence and compliance, adverse drug events in older people: a systematic review. Drug Saf. 2012;35:73-87.
10. Stevenson JM, Davies JG, Martin FC. Medication-related harm: a geriatric syndrome. Age and ageing. 2020;49(1):7-11.
11. Kocyigit SE, Bulut EA, Aydin AE, Dost FS, Kaya D, Isik AT. The relationship between cognitive frailty, physical frailty and malnutrition in Turkish older adults. Nutrition. 2024;126:112504.
12. Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC geriatrics. 2017;17:1-10.
13. Arik G, Varan HD, Yavuz BB, Karabulut E, Kara O, Kilic MK, et al. Validation of Katz index of independence in activities of daily living in Turkish older adults. Archives of Gerontology and Geriatrics. 2015;61(3):344-50.
14. Isik EI, Yilmaz S, Uysal I, Basar S. Adaptation of the Lawton Instrumental Activities of Daily Living Scale to Turkish: Validity and Reliability Study. Ann Geriatr Med Res. 2020;24(1):35-40.
15. Sarikaya D, Halil M, Kuyumcu ME, Kilic MK, Yesil Y, Kara O, et al. Mini nutritional assessment test long and short form are valid screening tools in Turkish older adults. Archives of Gerontology and Geriatrics. 2015;61(1):56-60.
16. Manea L, Gilbody S, Hewitt C, North A, Plummer F, Richardson R, et al. Identifying depression with the PHQ-2: A diagnostic meta-analysis. Journal of Affective Disorders. 2016;203:382-95.
17. Mitchell AJ. The Mini-Mental State Examination (MMSE): update on its diagnostic accuracy and clinical utility for cognitive disorders. Cognitive screening instruments: A practical approach. 2017:37-48.
18. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2001;56(3):M146-M57.
19. Kocyigit SE, Soysal P, Bulut EA, Aydin AE, Dokuzlar O, Isik AT. What is the relationship between frailty and orthostatic hypotension in older adults? Journal of geriatric cardiology: JGC. 2019;16(3):272.
20. Sugimoto T, Arai H, Sakurai T. An update on cognitive frailty: Its definition, impact, associated factors and underlying mechanisms, and interventions. Geriatrics & gerontology international. 2022;22(2):99-109.
21. Soares PSM, Gonzalez TN, Paludo CdS, Meucci RD. The role of physical vulnerability in the association between social activities and cognitive performance in rural older adults: A longitudinal study. The International Journal of Aging and Human Development. 2023;97(2):188-201.
22. Robertson DA, Savva GM, Kenny RA. Frailty and cognitive impairment—a review of the evidence and causal mechanisms. Ageing research reviews. 2013;12(4):840-51.
23. Jamsen KM, Gnjidic D, Hilmer SN, Ilomäki J, Le Couteur DG, Blyth FM, et al. Drug Burden Index and change in cognition over time in community-dwelling older men: the CHAMP study. Ann Med. 2017;49(2):157-64.
24. Gnjidic D, Le Couteur DG, Naganathan V, Cumming RG, Creasey H, Waite LM, et al. Effects of drug burden index on cognitive function in older men. J Clin Psychopharmacol. 2012;32(2):273-7.
25. Katipoglu B, Kurtbeyoglu S, Demir ZA, Mavioglu HL. The effect of the anticholinergic burden on mortality following elective cardiac surgery. Current Medical Research and Opinion. 2024;40(1):27-34.
26. Katipoglu B, Demircan SK, Naharci MI. Association of drug burden index with delirium in community-dwelling older adults with dementia: a longitudinal observational study. International Journal of Clinical Pharmacy. 2023;45(5):1267-76.
27. Porter B, Arthur A, Savva GM. How do potentially inappropriate medications and polypharmacy affect mortality in frail and non-frail cognitively impaired older adults? A cohort study. BMJ open. 2019;9(5):e026171.
28. Wastesson JW, Morin L, Tan EC, Johnell K. An update on the clinical consequences of polypharmacy in older adults: a narrative review. Expert opinion on drug safety. 2018;17(12):1185-96.
29. Mair A, Wilson M, Dreischulte T. Addressing the challenge of polypharmacy. Annu Rev Pharmacol Toxicol. 2020;60(1):661-81.
30. Naharci MI, Katipoglu B, Tasci I. Association of anticholinergic burden with undernutrition in older adults: A cross‐sectional study. Nutr Clin Pract. 2022;37(5):1215-24.
31. Borders C, Sajjadi SA. Diagnosis and management of cognitive concerns in the oldest-old. Curr Treat Options Neurol. 2021;23:1-18.