Use of CNS medications and cognitive decline in the aged: a longitudinal population-based study

Juha Puustinen, Janne Nurminen, Minna Löppönen, Tero Vahlberg, Raimo Isoaho, Ismo Räihä, Sirkka-Liisa Kivelä, Juha Puustinen, Janne Nurminen, Minna Löppönen, Tero Vahlberg, Raimo Isoaho, Ismo Räihä, Sirkka-Liisa Kivelä

Abstract

Background: Previous studies have found associations between the use of central nervous system medication and the risk of cognitive decline in the aged. Our aim was to assess whether the use of a single central nervous system (CNS) medication and, on the other hand, the combined use of multiple CNS medications over time are related to the risk of cognitive decline in an older (≥ 65 yrs) population that is cognitively intact at baseline.

Methods: We conducted a longitudinal population-based study of cognitively intact older adults. The participants were 65 years old or older and had Mini-Mental State Examination (MMSE) sum scores of 24 points or higher. The study included a 7.6-year follow-up. The use of benzodiazepines and related drugs (BZDs), antipsychotics (APs), antidepressants (ADs), opioids (Ops), anticholinergics (AChs) and antiepileptics (AEs) was determined at baseline and after a 7.6-years of the follow-up period. Cognitive functioning was used as an outcome variable measured with MMSE at baseline and at the mean follow-up of 7.6 years. Control variables were adjusted with analyses of covariance.

Results: After adjusting for control variables, the use of Ops and the concomitant use of Ops and BZDs as well as the use of Ops and any CNS medication were associated with cognitive decline. The use of AChs was associated with decline in cognitive functioning only in men.

Conclusions: Of all the CNS medications analyzed in this study, the use of Ops may have the greatest effect on cognitive functioning in the ageing population. Due to small sample sizes these findings cannot be generalized to the unselected ageing population. More studies are needed concerning the long-term use of CNS medications, especially their concomitant use, and their potential cognitive effects.

References

    1. Berg S, Dellasega C. The use of psychoactive medications and cognitive function in older adults. J Aging Health. 1996;8(1):136–149. doi: 10.1177/089826439600800107.
    1. Wright RM, Roumani YF, Boudreau R, Newman AB, Ruby CM, Studenski SA, Shorr RI, Bauer DC, Simonsick EM, Hilmer SN, Hanlon JT. Effect of central nervous system medication use on decline in cognition in community-dwelling older adults: findings from the Health, Aging And Body Composition Study. J Am Geriatr Soc. 2009;57(2):243–250. doi: 10.1111/j.1532-5415.2008.02127.x.
    1. Bierman EJ, Comijs HC, Gundy CM, Sonnenberg C, Jonker C, Beekman AT. The effect of chronic benzodiazepine use on cognitive functioning in older persons: good, bad or indifferent? Int J Geriatr Psychiatry. 2007;22(12):1194–1200. doi: 10.1002/gps.1811.
    1. Paterniti S, Dufouil C, Alperovitch A. Long-term benzodiazepine use and cognitive decline in the elderly: the Epidemiology of Vascular Aging Study. J Clin Psychopharmacol. 2002;22(3):285–293. doi: 10.1097/00004714-200206000-00009.
    1. Lagnaoui R, Begaud B, Moore N, Chaslerie A, Fourrier A, Letenneur L, Dartigues JF, Moride Y. Benzodiazepine use and risk of dementia: a nested case-control study. J Clin Epidemiol. 2002;55(3):314–318. doi: 10.1016/S0895-4356(01)00453-X.
    1. Hanlon JT, Horner RD, Schmader KE, Fillenbaum GG, Lewis IK, Wall WE, Landerman LR, Pieper CF, Blazer DG, Cohen HJ. Benzodiazepine use and cognitive function among community-dwelling elderly. Clin Pharmacol Ther. 1998;64(6):684–692. doi: 10.1016/S0009-9236(98)90059-5.
    1. Carriere I, Fourrier-Reglat A, Dartigues JF, Rouaud O, Pasquier F, Ritchie K, Ancelin ML. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study. Arch Intern Med. 2009;169(14):1317–1324. doi: 10.1001/archinternmed.2009.229.
    1. Han L, Agostini JV, Allore HG. Cumulative anticholinergic exposure is associated with poor memory and executive function in older men. J Am Geriatr Soc. 2008;56(12):2203–2210. doi: 10.1111/j.1532-5415.2008.02009.x.
    1. Ancelin ML, Artero S, Portet F, Dupuy AM, Touchon J, Ritchie K. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. Bmj. 2006;332(7539):455–459. doi: 10.1136/.
    1. Basu R, Dodge H, Stoehr GP, Ganguli M. Sedative-hypnotic use of diphenhydramine in a rural, older adult, community-based cohort: effects on cognition. Am J Geriatr Psychiatry. 2003;11(2):205–213.
    1. Bottiggi KA, Salazar JC, Yu L, Caban-Holt AM, Ryan M, Mendiondo MS, Schmitt FA. Long-term cognitive impact of anticholinergic medications in older adults. Am J Geriatr Psychiatry. 2006;14(11):980–984. doi: 10.1097/01.JGP.0000224619.87681.71.
    1. Isoaho R, Puolijoki H, Huhti E, Kivela SL, Tala E. Prevalence of asthma in elderly Finns. J Clin Epidemiol. 1994;47(10):1109–1118. doi: 10.1016/0895-4356(94)90097-3.
    1. Lopponen M, Raiha I, Isoaho R, Vahlberg T, Kivela SL. Diagnosing cognitive impairment and dementia in primary health care -- a more active approach is needed. Age Ageing. 2003;32(6):606–612. doi: 10.1093/ageing/afg097.
    1. Linjakumpu T, Hartikainen S, Klaukka T, Koponen H, Kivela SL, Isoaho R. Psychotropics among the home-dwelling elderly--increasing trends. Int J Geriatr Psychiatry. 2002;17(9):874–883. doi: 10.1002/gps.712.
    1. Linjakumpu T, Hartikainen S, Klaukka T, Veijola J, Kivela SL, Isoaho R. Use of medications and polypharmacy are increasing among the elderly. Journal of clinical epidemiology. 2002;55(8):809–817. doi: 10.1016/S0895-4356(02)00411-0.
    1. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–198. doi: 10.1016/0022-3956(75)90026-6.
    1. National Agency of Medicines. Classification of Medicines (ATC) and Defined Daily Doses (DDD) Helsinki; 1996.
    1. Socialstyrelsen. Indikatorer för utvärdering av kvaliteten i äldres läkemedelsterapi [Indicators for evaluating the quality of medication therapy in the aged] Stockholm; 2003. Report No.: 2003-110-20: 74.
    1. Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH. Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts. Arch Intern Med. 2003;163(22):2716–2724. doi: 10.1001/archinte.163.22.2716.
    1. Qiu C, De Ronchi D, Fratiglioni L. The epidemiology of the dementias: an update. Curr Opin Psychiatry. 2007;20(4):380–385. doi: 10.1097/YCO.0b013e32816ebc7b.
    1. Tangalos EG, Smith GE, Ivnik RJ, Petersen RC, Kokmen E, Kurland LT, Offord KP, Parisi JE. The Mini-Mental State Examination in general medical practice: clinical utility and acceptance. Mayo Clin Proc. 1996;71(9):829–837. doi: 10.4065/71.9.829.
    1. Kivela SL, Nissinen A, Ketola A, Punsar S, Puska P, Karvonen M. Changes in alcohol consumption during a ten-year follow-up among Finnish men aged 55-74 years. Funct Neurol. 1988;3(2):167–178.
    1. Puustinen J, Nurminen J, Kukola M, Vahlberg T, Laine K, Kivela SL. Associations between use of benzodiazepines or related drugs and health, physical abilities and cognitive function: a non-randomised clinical study in the elderly. Drugs Aging. 2007;24(12):1045–1059. doi: 10.2165/00002512-200724120-00007.
    1. Dealberto MJ, McAvay GJ, Seeman T, Berkman L. Psychotropic drug use and cognitive decline among older men and women. Int J Geriatr Psychiatry. 1997;12(5):567–574. doi: 10.1002/(SICI)1099-1166(199705)12:5<567::AID-GPS552>;2-V.
    1. Fastbom J, Forsell Y, Winblad B. Benzodiazepines may have protective effects against Alzheimer disease. Alzheimer Dis Assoc Disord. 1998;12(1):14–17. doi: 10.1097/00002093-199803000-00002.
    1. Legangneux E, McEwen J, Wesnes KA, Bergougnan L, Miget N, Canal M, L'Heritier C, Pinquier JL, Rosenzweig P. The acute effects of amisulpride (50 mg and 200 mg) and haloperidol (2 mg) on cognitive function in healthy elderly volunteers. J Psychopharmacol. 2000;14(2):164–171. doi: 10.1177/026988110001400206.
    1. Allain H, Tessier C, Bentue-Ferrer D, Tarral A, Le Breton S, Gandon M, Bouhours P. Effects of risperidone on psychometric and cognitive functions in healthy elderly volunteers. Psychopharmacology (Berl) 2003;165(4):419–429.
    1. Todorova A, Vonderheid-Guth B, Dimpfel W. Effects of tolterodine, trospium chloride, and oxybutynin on the central nervous system. J Clin Pharmacol. 2001;41(6):636–644. doi: 10.1177/00912700122010528.
    1. Pakulski C, Drobnik L, Millo B. Age and sex as factors modifying the function of the blood-cerebrospinal fluid barrier. Med Sci Monit. 2000;6(2):314–318.
    1. Starr JM, Wardlaw J, Ferguson K, MacLullich A, Deary IJ, Marshall I. Increased blood-brain barrier permeability in type II diabetes demonstrated by gadolinium magnetic resonance imaging. J Neurol Neurosurg Psychiatry. 2003;74(1):70–76. doi: 10.1136/jnnp.74.1.70.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi