Geriatrics update 2012: What parts of our practice to change, what to ‘think about’
ABSTRACTMany new guidelines and studies of interest to the geriatric population have emerged in the areas of falls and fracture prevention, cardiovascular care, depression, and Alzheimer disease. Some of these guidelines and studies translate to immediate changes that should be made to clinical practice; others are new areas of controversy.
KEY POINTS
- To prevent falls, patients should be asked not only about recent falls but about balance. Referral for a multicomponent falls evaluation should be considered.
- For patients age 80 and older, a target systolic blood pressure of 140 to 145 mm Hg is acceptable, and blood pressure below 130 mm Hg systolic and 65 mm Hg diastolic should be avoided.
- The dosage of the antidepressant citalopram (Celexa) should not exceed 40 mg per day in the general population and 20 mg in patients age 60 and older.
- Calcium supplementation may increase the risk of myocardial infarction and stroke. A large annual dose of vitamin D appears harmful, raising questions about the long-term safety of large doses given weekly or monthly.
DEPRESSION CAN BE EFFECTIVELY TREATED WITH MEDICATION
Many placebo-controlled trials have demonstrated the effectiveness of treating depression with medications in elderly people who are cognitively intact and living in the community. A Cochrane Review20 found that in placebo-controlled trials, the number needed to treat to produce one recovery with tricyclic antidepressants, selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors was less than 10 for each of the drug classes.
Since the newer drugs appear to be safer and to have fewer adverse effects than the older drugs, more older adults have been treated with antidepressants, including patients with comorbidities such as dementia that were exclusion criteria in early studies. For example, the number of older adults treated with antidepressants has increased 25% since 1992; at the same time the number being referred for cognitive-based therapies has been reduced by 43%.21 Similar trends are apparent in elderly people in long-term care. In 1999, about one-third of people in long-term care were diagnosed with depression; in 2007 more than one-half were.22
Treating depression is less effective when dementia is present
Up to half of adults age 85 and older living in the community may have dementia. In long-term care facilities, most residents likely have some cognitive impairment or are diagnosed with dementia. Many of these are also taking antidepressive agents.
A review of studies in the Medline and Cochrane registries found seven trials that treated 330 patients with antidepressants for combined depression and dementia. Efficacy was not confirmed.23
After this study was published, Banerjee et al24 treated 218 patients who had depression and dementia in nine centers in the United Kingdom. Patients received sertraline (Zoloft), mirtazapine (Remeron), or placebo. Reductions in depression scores at 13 weeks and at 39 weeks did not differ between the groups, and adverse events were more frequent in the treatment groups than in the placebo groups.
Comments. The poor performance of antidepressants in patients with dementia may be due to misdiagnosis, such as mistaking apathy for depression.25 It is also possible that better criteria than we have now are needed to diagnose depression in patients with dementia, or that current outcome measures are not sensitive for depression when dementia is present.
It may also be unsafe to treat older adults long-term with antidepressive agents. For example, although selective serotonin reuptake inhibitors, the most commonly prescribed antidepressive agents, are considered safe, their side effects are numerous and include sexual dysfunction, bleeding (due to platelet dysfunction), hyponatremia, early weight loss, tremor (mostly with paroxetine [Paxil]), sedation, apathy (especially with high doses), loose stools (with sertraline), urinary incontinence, falls, bone loss, and QTc prolongation.
Citalopram: Maximum dosage in elderly
In August 2011, an FDA Safety Communication was issued for citalopram (Celexa), stating that the daily dose should not exceed 40 mg in the general population and should not exceed 20 mg in patients age 60 and older. The dose should also not exceed 20 mg for a patient at any age who has hepatic impairment, who is known to be a poor metabolizer of CYP 2C19, or who takes cimetidine (Tagamet), since that drug inhibits the metabolism of citalopram at the CYP 2C19 enzyme site.
Although the FDA warning specifically mentions only cimetidine, physicians may have concerns about other drugs that inhibit CYP 2C19, such as proton pump inhibitors (eg, omeprazole [Prilosec]) when taken concomitantly with citalopram. Also, escitalopram (Lexapro) and sertraline are quite similar to citalopram; although they were not mentioned in the FDA Safety Communication, higher doses of these drugs may put patients at similar risk.
ALZHEIMER DISEASE: NEED TO BETTER IDENTIFY PEOPLE AT RISK
The definition of dementia is essentially the presence of a cognitive problem that affects the ability to function. For people with Alzheimer disease, impairment of cognitive performance precedes functional decline. Those with a cognitive deficit who still function well have, by definition, mild cognitive impairment (MCI). Although MCI could be caused by a variety of vascular and other neurologic processes, the most common cause of MCI in the United States is Alzheimer disease.
Unfortunately, the population with MCI currently enrolled in clinical trials to reduce the risk of progression to Alzheimer disease is heterogeneous. Many study participants may never get dementia, and others may have had the pathology present for decades and are progressing rapidly. Imaging and biomarkers are emerging as good indicators that predict progression and could help to better define populations for clinical trials.26
Studies now indicate that people with MCI that is ultimately due to Alzheimer disease are likely to have amyloid beta peptide 42 evident in the cerebrospinal fluid 10 to 20 years before symptoms arise. At the same time, amyloid is also likely to be evident in the brain with amyloid-imaging positron emission tomography (PET). Some time later, abnormalities in metabolism are also evident on fluorodeoxyglucose (FDG) PET, as are changes such as reduced hippocampal volume on magnetic resonance imaging (MRI).
The 1984 criteria for diagnosing MCI due to Alzheimer disease were recently revised to incorporate the evolving availability of biomarkers.27,28 The diagnosis of MCI itself is still based on clinical ascertainment including history, physical examination, and cognitive testing. It requires diagnosis of a cognitive decline from a prior level but maintenance of activities of daily living with no or minimal assistance. This diagnosis is certainly challenging since it requires ascertainment of a prior level of function and corroboration, when feasible, with an informant. Blood tests and imaging, which are readily available, constitute an important part of the assessment.
Attributing the MCI to Alzheimer disease requires consistency of the disease course—a gradual decline in Alzheimer disease, rather than a stroke, head injury, neurologic disease such as Parkinson disease, or mixed causes.
Knowledge of genetic factors, such as the presence of a mutation in APP, PS1, or PS2, can be predictive with young patients. The presence of one or two 34 alleles in the apolipoprotein E (APOE) gene is the only genetic variant broadly accepted as increasing the risk for late-onset Alzheimer dementia, whereas the 32 allele decreases risk.
Refining the risk attribution to Alzheimer disease requires biomarkers, currently available only in research settings:
- High likelihood—amyloid beta peptide detected by PET or cerebrospinal fluid analysis and evidence of neuronal degeneration or injury (elevated tau in the cerebrospinal fluid, decreased FDG uptake on PET, and atrophy evident by structural MRI)
- Intermediate likelihood—presence of amyloid beta peptide or evidence of neuronal degeneration or injury
- Unlikely—biomarkers tested and negative
- No comment—biomarkers not tested or reporting is indeterminate.
Comments. There is significant potential for misunderstanding the new definition for MCI. Patients who are concerned about their memory may request biomarker testing in an effort to determine if they currently have or will acquire Alzheimer disease. Doctors may be tempted to refer patients for biomarker testing (via imaging or lumbar puncture) to “screen” for MCI or Alzheimer disease.
It should be emphasized that MCI itself is still a clinical diagnosis, with the challenges noted above of determining whether there has been a cognitive decline from a prior level of function but preservation of activities of daily living. The biomarkers are not proposed to diagnose MCI, but only to help identify the subset of MCI patients most likely to progress rapidly to Alzheimer disease.
At present, the best use of biomarker testing is to aid research by identifying high-risk people among those with MCI who enroll in prospective trials for testing interventions to reduce the progression of Alzheimer disease.
