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Published in: BMC Geriatrics 1/2011

Open Access 01-12-2011 | Research article

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

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

Published in: BMC Geriatrics | Issue 1/2011

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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.
Literature
1.
go back to reference Berg S, Dellasega C: The use of psychoactive medications and cognitive function in older adults. J Aging Health. 1996, 8 (1): 136-149. 10.1177/089826439600800107.CrossRefPubMed Berg S, Dellasega C: The use of psychoactive medications and cognitive function in older adults. J Aging Health. 1996, 8 (1): 136-149. 10.1177/089826439600800107.CrossRefPubMed
2.
go back to reference 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. 10.1111/j.1532-5415.2008.02127.x.CrossRefPubMedPubMedCentral 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. 10.1111/j.1532-5415.2008.02127.x.CrossRefPubMedPubMedCentral
3.
go back to reference 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. 10.1002/gps.1811.CrossRefPubMed 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. 10.1002/gps.1811.CrossRefPubMed
4.
go back to reference 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. 10.1097/00004714-200206000-00009.CrossRefPubMed 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. 10.1097/00004714-200206000-00009.CrossRefPubMed
5.
go back to reference 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. 10.1016/S0895-4356(01)00453-X.CrossRefPubMed 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. 10.1016/S0895-4356(01)00453-X.CrossRefPubMed
6.
go back to reference 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. 10.1016/S0009-9236(98)90059-5.CrossRefPubMed 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. 10.1016/S0009-9236(98)90059-5.CrossRefPubMed
7.
go back to reference 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. 10.1001/archinternmed.2009.229.CrossRefPubMedPubMedCentral 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. 10.1001/archinternmed.2009.229.CrossRefPubMedPubMedCentral
8.
go back to reference 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. 10.1111/j.1532-5415.2008.02009.x.CrossRefPubMedPubMedCentral 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. 10.1111/j.1532-5415.2008.02009.x.CrossRefPubMedPubMedCentral
9.
go back to reference 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. 10.1136/bmj.38740.439664.DE.CrossRefPubMedPubMedCentral 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. 10.1136/bmj.38740.439664.DE.CrossRefPubMedPubMedCentral
10.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
11.
go back to reference 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. 10.1097/01.JGP.0000224619.87681.71.CrossRefPubMed 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. 10.1097/01.JGP.0000224619.87681.71.CrossRefPubMed
12.
go back to reference Isoaho R, Puolijoki H, Huhti E, Kivela SL, Tala E: Prevalence of asthma in elderly Finns. J Clin Epidemiol. 1994, 47 (10): 1109-1118. 10.1016/0895-4356(94)90097-3.CrossRefPubMed Isoaho R, Puolijoki H, Huhti E, Kivela SL, Tala E: Prevalence of asthma in elderly Finns. J Clin Epidemiol. 1994, 47 (10): 1109-1118. 10.1016/0895-4356(94)90097-3.CrossRefPubMed
13.
go back to reference 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. 10.1093/ageing/afg097.CrossRefPubMed 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. 10.1093/ageing/afg097.CrossRefPubMed
14.
go back to reference 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. 10.1002/gps.712.CrossRefPubMed 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. 10.1002/gps.712.CrossRefPubMed
15.
go back to reference 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. 10.1016/S0895-4356(02)00411-0.CrossRefPubMed 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. 10.1016/S0895-4356(02)00411-0.CrossRefPubMed
16.
go back to reference 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. 10.1016/0022-3956(75)90026-6.CrossRefPubMed 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. 10.1016/0022-3956(75)90026-6.CrossRefPubMed
17.
go back to reference National Agency of Medicines: Classification of Medicines (ATC) and Defined Daily Doses (DDD). 1996, Helsinki National Agency of Medicines: Classification of Medicines (ATC) and Defined Daily Doses (DDD). 1996, Helsinki
18.
go back to reference Socialstyrelsen: Indikatorer för utvärdering av kvaliteten i äldres läkemedelsterapi [Indicators for evaluating the quality of medication therapy in the aged]. 2003, Stockholm, Report No.: 2003-110-20: 74 Socialstyrelsen: Indikatorer för utvärdering av kvaliteten i äldres läkemedelsterapi [Indicators for evaluating the quality of medication therapy in the aged]. 2003, Stockholm, Report No.: 2003-110-20: 74
19.
go back to reference 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. 10.1001/archinte.163.22.2716.CrossRefPubMed 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. 10.1001/archinte.163.22.2716.CrossRefPubMed
20.
go back to reference Qiu C, De Ronchi D, Fratiglioni L: The epidemiology of the dementias: an update. Curr Opin Psychiatry. 2007, 20 (4): 380-385. 10.1097/YCO.0b013e32816ebc7b.CrossRefPubMed Qiu C, De Ronchi D, Fratiglioni L: The epidemiology of the dementias: an update. Curr Opin Psychiatry. 2007, 20 (4): 380-385. 10.1097/YCO.0b013e32816ebc7b.CrossRefPubMed
21.
go back to reference 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. 10.4065/71.9.829.CrossRefPubMed 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. 10.4065/71.9.829.CrossRefPubMed
22.
go back to reference 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.PubMed 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.PubMed
23.
go back to reference 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. 10.2165/00002512-200724120-00007.CrossRefPubMed 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. 10.2165/00002512-200724120-00007.CrossRefPubMed
24.
go back to reference 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. 10.1002/(SICI)1099-1166(199705)12:5<567::AID-GPS552>3.0.CO;2-V.CrossRefPubMed 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. 10.1002/(SICI)1099-1166(199705)12:5<567::AID-GPS552>3.0.CO;2-V.CrossRefPubMed
25.
go back to reference Fastbom J, Forsell Y, Winblad B: Benzodiazepines may have protective effects against Alzheimer disease. Alzheimer Dis Assoc Disord. 1998, 12 (1): 14-17. 10.1097/00002093-199803000-00002.CrossRefPubMed Fastbom J, Forsell Y, Winblad B: Benzodiazepines may have protective effects against Alzheimer disease. Alzheimer Dis Assoc Disord. 1998, 12 (1): 14-17. 10.1097/00002093-199803000-00002.CrossRefPubMed
26.
go back to reference 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. 10.1177/026988110001400206.CrossRefPubMed 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. 10.1177/026988110001400206.CrossRefPubMed
27.
go back to reference 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. 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.
28.
go back to reference 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. 10.1177/00912700122010528.CrossRefPubMed 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. 10.1177/00912700122010528.CrossRefPubMed
29.
go back to reference 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.PubMed 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.PubMed
30.
go back to reference 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. 10.1136/jnnp.74.1.70.CrossRefPubMedPubMedCentral 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. 10.1136/jnnp.74.1.70.CrossRefPubMedPubMedCentral
Metadata
Title
Use of CNS medications and cognitive decline in the aged: a longitudinal population-based study
Authors
Juha Puustinen
Janne Nurminen
Minna Löppönen
Tero Vahlberg
Raimo Isoaho
Ismo Räihä
Sirkka-Liisa Kivelä
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Geriatrics / Issue 1/2011
Electronic ISSN: 1471-2318
DOI
https://doi.org/10.1186/1471-2318-11-70

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