In people without cognitive impairment or with mild cognitive impairment, drug treatments do not prevent or delay dementia or cognitive decline

Fink HA, Jutkowitz E, McCarten JR, et al. Pharmacologic Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review. Ann Intern Med. 2018;168:39-51.

Review question

In people with normal cognition or mild cognitive impairment, can drug treatment prevent or delay loss of cognitive function (e.g., thinking, learning, remembering) or dementia?

Background

Cognitive function includes abilities such as thinking, remembering, using language, and making decisions. As we get older, our cognitive functions may decline. Mild cognitive impairment includes cognitive changes that are noticeable but usually don’t have much effect on daily living. Dementia is cognitive impairment that is serious enough to interfere with daily living.

Some drugs have been used to try to prevent or delay cognitive decline. However, we don’t know which drugs, if any, are effective. This review focused on drugs to prevent or delay dementia either due to Alzheimer disease or to unknown causes. Dementia due to repeated strokes was not included.

How the review was done

Researchers in the USA did a systematic review of studies available up to July 2017. They analyzed 51 studies of moderate or good quality. Most studies were randomized controlled trials.

Key features of the studies were:

• people were adults with normal cognition or mild cognitive impairment;
• people with dementia were excluded;
• prescription drugs that were approved by the US Food and Drug Administration were evaluated;
• drugs included nonsteroidal anti-inflammatory drugs (NSAIDs) (aspirin, celecoxib, naproxen), dementia drugs (cholinesterase inhibitors including donepezil), statins (atorvastatin, lovastatin, pravastatin, simvastatin), antidiabetes drugs (insulin glargine, metformin, pioglitazone), antihypertension drugs (amiloride, atenolol, candesartan, captopril, chlorthalidone, enalapril, hydralazine, hydrocholorthiazide, indapamide, isradipine, lisinopril, losartan, methyldopa, metoprolol, nifedipine, nitrendipine, perindopril, ramipril, reserpine, telmisartan), hormone therapies (estrogen with or without progestin, testosterone), and selective estrogen receptor modulators (raloxifene);
• drugs were mostly compared with placebo; some drugs were compared with other drugs or more intensive drug doses;
• people were followed for at least 6 months; and
• 63% of studies were fully or partly funded by industry.

What the researchers found

Most of the evidence was of low strength (confidence in results was limited) or insufficient to reach any conclusions.

We have mainly reported results for dementia and mild cognitive impairment outcomes here. If that information wasn’t available, we reported results for cognitive function tests. We have not reported results with insufficient evidence.

Results in adults with normal cognition (all low-strength evidence)

Compared with placebo (also see Table below):

• raloxifene, 120 mg/day, reduced risk for mild cognitive impairment but not dementia;
• estrogen increased risk for dementia or mild cognitive impairment;
• estrogen plus progestin increased risk for dementia but not mild cognitive impairment; and
• antihypertension drugs and NSAIDs had no effect on risk for dementia.

In drug vs drug comparisons:

• different antihypertension drug regimens did not differ from one another for reducing the risk for new cognitive impairment at 5 years in 1 study of 25,620 people or for improving performance on cognitive function tests at 6 to 9 months in 3 studies of 2,614 people; and
• statin drugs plus fenofibrate did not improve performance on cognitive function tests compared with statin drugs alone at 3 years in 1 study of 1,538 people.

Results in adults with mild cognitive impairment (all low-strength evidence)

Compared with placebo:

• dementia medications (cholinesterase inhibitors) did not reduce risk for dementia at 3 years in 1 study of 512 people; and
• neither dementia medications (cholinesterase inhibitors) in 2 studies of 533 people nor testosterone in 2 studies of 515 people improved performance on cognitive function tests at 6 months to 3 years.

Conclusion

In people with normal cognition or mild cognitive impairment, drug treatments don’t prevent dementia or delay loss of cognitive function.

Drugs vs placebo in adults with normal cognition

NSAID = nonsteroidal anti-inflammatory drug.

*Low strength of evidence = limited confidence in results.