Alzheimers Dement 2013 Nov 01;9(6)724-732, KR Obermann, JC Morris, CM Roe Research · December 19, 2013

Practice Update Website Story:  http://www.practiceupdate.com/journalscan/7193
Journal Abstract:  http://www.alzheimersanddementia.com/article/S1552-5260(12)02574-5/abstract

TAKE-HOME MESSAGE

Results of this exploratory analysis of 100 drugs showed that common medications used by older adults, 10% in this study, are associated with increases or decreases in cognitive performance.
Further studies investigating medication use and its effect on cognitive performance in older adults are needed.

Commentary By:  Irene Mace Hamrick MD, FAAFP, AGSF

The author takes a unique approach of looking at the 100 drugs most commonly used by older adults to determine the effect on cognition. Six drugs or supplements were associated with improved cognition, and three with worsened cognition.

Between writing and publication of this article, the revised Beers criteria1 were published with a good evidence base supporting inappropriate medications in older adults. Three drugs from this study, naproxen, sertraline, and oxybutynin, are also listed in the Beers Criteria, albeit for different reasons than cognition.

• Naproxen has been shown to improve cognition in this study; however, ibuprofen, used more frequently at 6.8% vs 5.6%, did not seem to have an impact. Nonsteroidal anti-inflammatory drugs and Cox-2 inhibitors have been shown to increase kidney injury and heart failure in older adults,1 and use needs to be closely monitored.
• Sertraline has been shown to improve cognition in this study but is associated with delirium from hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion.1 SSRIs increase the risk of falls,1 with a threefold increase in nursing home patients.2
• Oxybutynin has been shown to worsen cognition and is also listed by the Beers Criteria because of its anticholinergic effects, which are associated with delirium and cognitive impairment.1
• Furosemide has been found to worsen cognition in this study, even after controlling for congestive heart failure. The author suspected electrolyte abnormalities to be the culprit, a reasonable conclusion after potassium was associated with improved cognition. I suspect that dehydration may be contributing, which would explain why stopping the med did not improve cognition. Dehydration has been shown to cause delirium and cognitive impairment.3 It is, therefore, important to follow-up furosemide treatment with laboratory checks for dehydration and treat with as little furosemide as possible.
• In this study, five different statins appeared to have no effect on cognition. Previously, one small (n = 18) prospective trial showed that stopping statins improved cognition in patients with Alzheimer’s dementia, which worsened with restarting the statin.4 Yet, a recent systematic review of observational studies showed no effect of statins on cognition.5

With any change in medication, we should ask family to monitor cognition as the patients themselves often are unaware of changes.

Most medication trials excluded older adults because of their comorbidities and polypharmacy.6 Even when older adults were included, rarely did trials include cognitively impaired patients or monitor cognitive effects.

1. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012;60(4):616-631.
2. Sterke CS, Ziere G, van Beeck EF, et al. Dose-response relationship between selective serotonin re-uptake inhibitors and injurious falls: a study in nursing home residents with dementia. Br J Clin Pharmacol. 2012;73(5):812-820.
3. Carrasco MP, Villarroel L, Andrade M, et al. Development and validation of a delirium predictive score in older people [published online ahead of print September 24, 2013]. Age Ageing. doi: 10.1093/ageing/aft141.
4. Padala KP, Padala PR, McNeilly DP,et al. The effect of HMG-CoA reductase inhibitors on cognition in patients with Alzheimer’s dementia: a prospective withdrawal and rechallenge pilot study. Am J Geriatr Pharmacother. 2012;10(5):296-302.
5. Richardson K, Schoen M, French B, et al. Statins and cognitive function: a systematic review. Ann Intern Med. 2013;159(10):688-697.
6. Watts G. Why the exclusion of older people from clinical research must stop. BMJ. 2012;344:e3445. doi: 10.1136/bmj.e3445.

ABSTRACT

BACKGROUND

There are conflicting reports and a lack of evidence-based data regarding effects of medications on cognition in cognitively normal older adults. We explored whether use of 100 common medications taken by older adults is associated with longitudinal cognitive performance.

METHODS

A longitudinal observational cohort was used with analysis of data collected from September 2005 through May 2011 and maintained in the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set. Participants were aged 50 years or older and cognitively normal (N = 4414). Composite scores were constructed from 10 psychometric tests. Scores for each participant reflecting change in the psychometric composite score from the baseline clinical assessment to the next assessment were calculated. General linear models were used to test whether the mean composite change score differed for participants who reported starting, stopping, continuing, or not taking each of the 100 most frequently used medications in the NACC sample.

RESULTS

The average time between assessments was 1.2 years (SD = 0.42). Nine medications showed a difference (P < .05) across the four participant groups in mean psychometric change scores from the first to the second assessment. Medications associated with improved psychometric performance were naproxen, calcium-vitamin D, ferrous sulfate, potassium chloride, flax, and sertraline. Medications associated with declining psychometric performance were bupropion, oxybutynin, and furosemide.

CONCLUSIONS

Reported use of common medications is associated with cognitive performance in older adults, but studies are needed to investigate the mechanisms underlying these effects.