There’s no gold standard list of drugs that affect cognition in cognitively normal older adults, say researchers from St. Louis College of Pharmacy, Knight Alzheimer’s Disease Research Center, and Washington University School of Medicine, all in St. Louis, Missouri. That means physicians and pharmacists must rely on prescribing guides, such as the Beers criteria, which are based on consensus but lack supporting data. So as a “first step in addressing this lack of knowledge,” the researchers examined the long-term effects of the top 100 medications used by 4,414 participants in the National Alzheimer’s Coordinating Center database. They found that roughly 10% of those drugs were associated with long-term changes in cognition.
The researchers divided the patients into 4 groups: Group 1 was not taking the drug at visit 1 but was at visit 2; Group 2 stopped taking the drug between visit 1 and visit 2; Group 3 did not take the drug; and Group 4 was taking the drug at both visits. Composite scores were constructed from 10 psychometric tests. The researchers looked at change in cognition from the baseline visit to the follow-up visit, also looking for changes in or maintenance of the use of each medication. The average time between assessments was 1.2 years.
Nine drugs were associated with a statistically significant difference between at least 2 of the 4 study groups (P < .05). Naproxen, calcium-vitamin D, ferrous sulfate, potassium chloride, flax, and sertraline were all associated with improved psychometric performance. Bupropion, oxybutynin, and furosemide were associated with declines. Ferrous sulfate was associated with changes in attention, processing speed, and episodic memory, whereas the other 8 drugs were associated mainly with changes in attention and processing speed.
The drugs that improved cognition did so by a variety of proposed mechanisms. Naproxen may have improved scores by relieving pain, which can impede performance. Vitamin D deficiency is linked to reduced cognition in older adults, and ferrous sulfate is used to treat anemia; correcting those deficiencies may have helped cognition. Potassium chloride is used to treat or prevent hypokalemia, which can lead to confusion and cognitive problems; in this study, participants who stopped taking potassium showed drops in change scores compared with those who continued taking it.
Flax was an outlier in that the researchers were puzzled by its connection to better cognition. They did note, however, that people taking flax seed were also usually taking calcium-vitamin D. They hypothesize that people who take flax are likely to take other medicines or supplements that improve cognition. Sertraline has been shown to improve immediate and delayed verbal recall in older adults and to have a better effect on cognition than other selective serotonin reuptake inhibitors.
Some of their findings were new, the researchers say, such as the potential positive effects of ferrous sulfate. Similarly, bupropion has not previously been linked to negative effects on cognition in older adults. Such data deserve more examination, they say. Future studies may also show whether those drugs could delay the onset of incident dementia.
Source
Obermann KR, Morris JC, Roe CM. Alzheimers Dement. 2013;9(6):724-732.
doi: 10.1016/j.jalz.2012.12.002.