CNS medications as predictors of precipitous cognitive decline in the cognitively disabled aged: a longitudinal population-based study

Juha Puustinen, Janne Nurminen, Tero Vahlberg, Alan Lyles, Raimo Isoaho, Ismo Räihä, Sirkka-Liisa Kivelä, Juha Puustinen, Janne Nurminen, Tero Vahlberg, Alan Lyles, Raimo Isoaho, Ismo Räihä, Sirkka-Liisa Kivelä

Abstract

Background/aims: Psychotropics and antiepileptics (AE) are medications commonly used among the aged with cognitive decline or dementia, although they may precipitate further cognitive decline. Our aim was to analyze the relationships between the use of (i) psychotropics (i.e. benzodiazepines or related drugs, BZD, antipsychotics, AP, or antidepressants, AD), opioids (Op), anticholinergics (ACh) or AEs or the concomitant use of two of these drugs, and (ii) the risk of precipitous cognitive decline in an older (≥65 years) cognitively disabled population.

Methods: A longitudinal population-based study of general aged community-dwelling patients was executed in two phases (1990-1991 and 1998-1999) in Lieto, Finland. Fifty-two individuals cognitively disabled (MMSE score 0-23) at the 1990-1991 baseline form this study's sample. Cognitive abilities were assessed in each phase with the Mini-Mental State Examination (MMSE) and medication utilization data were collected in both phases. The mean follow-up time was 7.6 years. Multivariate models were used to analyze the change in MMSE total score between medication users and non-users.

Results: BZD or any psychotropic use was associated with greater cognitive decline in elders aged ≥75 years compared to non-users (change in MMSE sum score: -8.6 ± 7.0 vs. -3.3 ± 5.6 and -5.9 ± 7.0 vs. -2.7 ± 6.4, respectively). A greater decline was also associated specifically with the concomitant use of BZD and AP (-16 vs. -1.4 ± 7.8); as were BZD and any drug with CNS effects (-9.6 ± 9.9 vs. -1.3 ± 7.2) compared to non-users. The concomitant use of BZD and AD (-10.7 ± 4.7 vs. -3.2 ± 5.6) or ACh (-15.0 ± 8.5 vs. -3.3 ± 5.6) or any drug with CNS effects (-13.3 ± 6.5 vs. -3.3 ± 5.6) was associated with cognitive decline in patients ≥75 years compared to non-users of any drug with CNS effects.

Conclusion: The use of a BZD or any psychotropic medication may be an independent risk factor for cognitive decline in the cognitively disabled aged, and patients co-prescribed psychotropic medications had greater cognitive decline. Studies with larger sample sizes and studies on possible pathophysiologic mechanisms are needed.

Keywords: Aged; Amnestic disorders; Benzodiazepines; CNS agents; Cholinergic antagonists; Cognitive disorders; Delirium disorders; Dementia disorders; Memory disorders; Parasympatholytics.

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