Medical Grand Rounds

What’s new in treating older adults?

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ABSTRACTClinical trials in the past few years have yielded findings that are relevant for clinical practice, not just for geriatricians but for all physicians who have elderly patients.

KEY POINTS

  • Exercise has newly discovered benefits, such as preserving cognition and boosting the response to vaccination.
  • Vitamin D supplementation has been found to prevent fractures, but yearly megadoses had the opposite effect.
  • Denosumab (Prolia) has been approved for preventing fractures. It acts by inhibiting the receptor activator of nuclear factor kappa B (RANK) ligand.
  • The outlook for elderly patients starting hemodialysis is bleak, with loss of function and a high risk of death.
  • Dabigatran (Pradaxa), a direct thrombin inhibitor, may prove to be a safer alternative to warfarin (Coumadin).
  • Cholinesterase inhibitors for Alzheimer disease are associated with higher risks of hospitalization for syncope, hip fractures, bradycardia, and pacemaker insertion.
  • The Clinical Dementia Rating should be estimated when prescribing a cognitive enhancer and when advising a patient with memory impairment on driving safety.
  • Delirium often accelerates dementia; interventions for hospitalized elderly patients may reduce its incidence.


 

References

New clinical trials and observational studies are shedding light on ways to improve the health of elderly patients. Here is a brief summary of these trials and how they might influence your clinical practice.

EXERCISE HAS NEWLY DISCOVERED BENEFITS

According to government data,1 exercise has a dose-dependent effect on rates of all-cause mortality: the more hours one exercises per week, the lower the risk of death. The difference in risk is most pronounced as one goes from no exercise to about 3 hours of exercise per week; above 3 hours per week, the curve flattens out but continues to decline. Hence, we advise patients to engage in about 30 minutes of moderate-intensity exercise every day.

Lately, physical exercise has been found to have other, unexpected benefits.

Exercise helps cognition

ERICKSON KI, PRAKASH RS, VOSS MW, ET AL. AEROBIC FITNESS IS ASSOCIATED WITH HIPPOCAMPAL VOLUME IN ELDERLY HUMANS. HIPPOCAMPUS 2009; 19:1030–1039.

ETGEN T, SANDER D, HUNTGEBURTH U, POPPERT H, FÖRSTL H, BICKEL H. PHYSICAL ACTIVITY AND INCIDENT COGNITIVE IMPAIRMENT IN ELDERLY PERSONS: THE INVADE STUDY. ARCH INTERN MED 2010; 170:186–193.

The hippocampus is a structure deep in the brain that is involved in short-term memory. It atrophies with age, more so with dementia. Erickson2 found a correlation between aerobic fitness (as measured by maximum oxygen consumption), hippocampal volume, and spatial memory performance.

Etgen and colleagues3 studied nearly 4,000 older adults in Bavaria for 2 years. Among those reporting no physical activity, 21.4% had cognitive impairment at baseline, compared with 7.3% of those with high activity at baseline. Following those without cognitive impairment over a 2-year period, they found the incidence of new cognitive impairment was 13.9% in those with no physical activity at baseline, 6.7% in those with moderate activity, and 5.1% in those with high activity.

Exercise boosts the effect of influenza vaccine

WOODS JA, KEYLOCK KT, LOWDER T, ET AL. CARDIOVASCULAR EXERCISE TRAINING EXTENDS INFLUENZA VACCINE SEROPROTECTION IN SEDENTARY OLDER ADULTS: THE IMMUNE FUNCTION INTERVENTION TRIAL. J AM GERIATR SOC 2009; 57:2183–2191.

In a study in 144 sedentary but healthy older adults (ages 60 to 83), Woods et al4 randomized the participants to undergo either flexibility or cardiovascular training for 10 months, starting 4 months before their annual influenza shot. Exercise extended the duration of antibody protection, with more participants in the cardiovascular group than in the flexibility group showing protection at 24 weeks against all three strains covered by the vaccine: H1N1, H3N2, and influenza B.

PREVENTING FRACTURES

Each year, about 30% of people age 65 or older fall, sustaining serious injuries in 5% to 10% of cases. Unintentional falls are the main cause of hip fractures, which number 300,000 per year. They are also a common cause of death.

Vitamin D prevents fractures, but can there be too much of a good thing?

BISCHOFF-FERRARI HA, WILLETT WC, WONG JB, ET AL. PREVENTION OF NONVERTEBRAL FRACTURES WITH ORAL VITAMIN D AND DOSE DEPENDENCY: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS. ARCH INTERN MED 2009; 169:551–561.

SANDERS KM, STUART AL, WILLIAMSON EJ, ET AL. ANNUAL HIGH-DOSE ORAL VITAMIN D AND FALLS AND FRACTURES IN OLDER WOMEN: A RANDOMIZED CONTROLLED TRIAL. JAMA 2010; 303:1815–1822.

Bischoff-Ferrari5 performed a meta-analysis of 12 randomized controlled trials of oral supplemental vitamin D3 for preventing nonvertebral fractures in people age 65 and older, and eight trials for preventing hip fractures in the same age group. They found that the higher the daily dose of vitamin D, the lower the relative risk of hip fracture. The threshold dose at which supplementation significantly reduced the risk of falling was about 400 units per day. Higher doses of vitamin D reduced both falls and hip fractures by about 20%. The maximal effect was seen with studies using the maximum daily doses, ie, 770 to 800 units per day—not megadoses, but more than most Americans are taking. The threshold serum level of vitamin D of significance was 60 nmol/L (24 ng/mL).

Of interest, the effect on fractures was independent of calcium supplementation. This is important because calcium supplementation over and above ordinary dietary intake may increase the risk of cardiovascular events.6,7

Despite the benefits of vitamin D, too much may be too much of a good thing. Sanders et al8 performed a double-blind, placebo-controlled trial in 2,256 community-dwelling women, age 70 or older, who were considered to be at high risk for fractures. Half received a large oral dose (500,000 units) once a year for 3 to 5 years, and half got placebo. Their initial serum vitamin D level was 49 nmol/L; the level 30 days after a dose in the treatment group was 120 nmol/L.

Contrary to expectations, the incidence of falls was 15% higher in the vitamin D group than in the placebo group (P = .03), and the incidence of fractures was 26% higher (P = .047). The falls and fractures tended to cluster in the first 3 months after the dose in the active treatment group, when serum vitamin D levels were highest.

Comments. Unless future studies suggest a benefit to megadoses of vitamin D or prove calcium supplementation greater than 1,000 mg is safe, the optimal daily intake of vitamin D is likely 1,000 units, with approximately 200 units from diet and 800 units from supplements. A diet rich in low-fat dairy products may not require calcium supplementation. In those consuming a low-calcium diet, supplements of 500 to 1,000 mg/day are likely adequate.

Denosumab, a new drug for preventing fractures

CUMMINGS SR, SAN MARTIN J, MCCLUNG MR, ET AL; FREEDOM TRIAL. DENOSUMAB FOR PREVENTION OF FRACTURES IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS. N ENGL J MED 2009; 361:756–765.

SMITH MR, EGERDIE B, HERNÁNDEZ TORIZ N, ET AL; DENOSUMAB HALT PROSTATE CANCER STUDY GROUP. DENOSUMAB IN MEN RECEIVING ANDROGEN-DEPRIVATION THERAPY FOR PROSTATE CANCER. N ENGL J MED 2009; 361:745–755.

Denosumab (Prolia) is the first of a new class of drugs for the treatment of osteoporosis. It is a monoclonal antibody and member of the tumor necrosis factor superfamily that binds to the receptor activator nuclear factor kappa B (RANK) ligand. It has an antiresorptive effect, preventing osteoclast differentiation and activation. It is given by subcutaneous injection of 60 mg every 6 months; it is cleared by a nonrenal mechanism.

In a randomized controlled trial in 7,868 women between the ages of 60 and 90 who had osteoporosis, Cummings et al9 reported that denosumab reduced the 3-year incidence of vertebral fractures by 68% (P < .001), reduced the incidence of hip fractures by 40% (P = .01), and reduced the incidence of nonvertebral fractures by 20% (P = .01). In a trial in men receiving androgen deprivation therapy for prostate cancer, Smith et al10 reported that denosumab reduced the incidence of vertebral fracture by 62% (P = .006).

Comment. Denosumab was approved by the US Food and Drug Administration (FDA) on June 1, 2010, and is emerging in specialty clinics at the time of this publication. Its potential impact on clinical care is not yet known. It is costly—about $825 (average wholesale price) per injection—but since it is given by injection it may be easier than a yearly infusion of zoledronic acid (Reclast). It has the potential to suppress immune function, although this was not reported in the clinical trials. It may ultimately have a role in treating osteoporosis in men and women, prostate cancer following androgen deprivation, metastatic prostate cancer, metastatic breast cancer, osteoporosis with renal impairment, and other diseases.

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