Current Interventions for Geriatric Cognitive Health

By Luke D. Kim, MD, FACP, CMD Ardeshir Z. Hashmi, MD, FACP

With the exception of oral anticoagulation treatment for atrial fibrillation, there is little evidence that pharmacologic or nonpharmacologic interventions slow the onset or progression of Alzheimer disease.

Nonpharmacologic interventions

Home occupational therapy. A two-year home-based occupational therapy intervention showed no evidence of slowing functional decline in patients with Alzheimer disease. The randomized controlled trial involving 180 participants consisted of monthly sessions of an intensive, well-established collaborative-care management model that included fall prevention and other safety strategies, personalized training in activities of daily living, exercise and education. Outcome measures for activities of daily living did not differ significantly between the treatment and control groups.

Physical activity. Whether physical activity interventions slow cognitive decline and prevent dementia in cognitively intact adults was examined in a systematic review of 32 trials. Most of the trials followed patients for six months; a few stretched for one or two years.

Evidence was insufficient to prove cognitive benefit for short-term, single-component or multicomponent physical activity interventions. However, a multidomain physical activity intervention that also included dietary modifications and cognitive training did show a delay in cognitive decline, but only low-strength evidence.

Nutritional supplements. The antioxidants vitamin E and selenium were studied for their possible cognitive benefit in the double-blind randomized Prevention of Alzheimer Disease by Vitamin E and Selenium trial in 3,786 asymptomatic men ages 60 and older. Neither supplement was found to prevent dementia over a seven-year follow-up period.

A review of 38 trials evaluated the effects on cognition of omega-3 fatty acids, soy, ginkgo biloba, B vitamins, vitamin D plus calcium, vitamin C, beta-carotene and multi-ingredient supplements. It found insufficient evidence to recommend any over-the-counter supplement for cognitive protection in adults with normal cognition or mild cognitive impairment.

Pharmacologic treatments

Testosterone supplementation. The Testosterone Trials tested the effects of testosterone gel versus placebo for one year on 493 men over age 65 with low testosterone (< 275 ng/mL) and with subjective memory complaints and objective memory performance deficits. Treatment was not associated with improved memory or other cognitive functions compared with placebo.

Antiamyloid drugs. A randomized, double-blind, placebo-controlled trial in nearly 2,000 patients evaluated verubecestat, an oral beta-site amyloid precursor protein-cleaving enzyme-1 inhibitor that reduces the amyloid-beta level in cerebrospinal fluid.

Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer disease, while adverse events including rashes, falls, injuries, sleep disturbances, suicidal ideation, weight loss and hair color change were more common in the treatment groups. The trial was terminated early because of futility at 50 months.

And in a placebo-controlled trial of solanezumab, a monoclonal antibody directed against the amyloid beta peptide, no benefit was demonstrated at 80 weeks in more than 2,000 patients with Alzheimer disease.

Multiple common agents. A well-conducted systematic review of 51 trials of at least a six-month duration did not support the use of antihypertensive agents, diabetes medications, nonsteroidal anti-inflammatory drugs, aspirin, hormones or lipid-lowering drugs for cognitive protection for people with normal cognition or mild cognitive impairment.

However, some studies found reassuring evidence that standard therapies for other conditions do not worsen cognitive decline and are protective for atrial fibrillation.

Proton-pump inhibitors. Concern exists for a potential link between dementia risk and proton-pump inhibitors, which are widely used to treat acid-related gastrointestinal disorders.

A prospective population-based cohort study of nearly 3,500 people ages 65 and older without baseline dementia screened participants for dementia every two years over a mean period of 7.5 years and provided further evaluation for those who screened positive. Use of proton-pump inhibitors was not found to be associated with dementia risk, even with high cumulative exposure.

Results from this study do not support avoiding proton-pump inhibitors out of concern for dementia risk, although long-term use is associated with other safety concerns.

Oral anticoagulation. The increased risk of dementia with atrial fibrillation is well-documented.

A retrospective study based on a Swedish health registry and using more than 444,000 patients covering more than 1.5 million years at risk found that oral anticoagulant treatment at baseline conferred a 29 percent lower risk of dementia in an intention-to-treat analysis and a 48 percent lower risk in on-treatment analysis compared with no oral anticoagulation therapy. No difference was found between new oral anticoagulants and warfarin.

This abridged article originally appeared in Cleveland Clinic Journal of Medicine.

Dr. Kim is staff in the Center for Geriatric Medicine. Dr. Hashmi directs the Center for Geriatric Medicine.