Geriatrics update 2015: Vaccination, frailty, chronic disease guidelines, and cognition
ABSTRACTThis paper discusses recent developments and recommendations for elderly patients concerning immunizations, heart failure, lipid therapy, blood pressure control, and dementia.
KEY POINTS
- Vaccination costs will increase—with unclear added value—with new guidelines for influenza and pneumococcal vaccines.
- Multiple simultaneous interventions for heart failure have additive value. These are education, a beta-blocker, an angiotensin-converting enzyme inhibitor, and, in some, an aldosterone antagonist, anticoagulation for atrial fibrillation, and an implantable cardioverter-defibrillator or cardiac resynchronization therapy.
- Statin therapy should be intensified with an eye to goals of care and tolerability rather than a specific lipid goal.
- Exercise improves physical and mental health in all, including the elderly.
- Dementia still has no magic bullet. Selective serotonin reuptake inhibitors might help behavior issues, and vitamin E might bring modest cognitive improvement but with possible risk.
SLOWING DEMENTIA IS STILL AN ELUSIVE GOAL
Vitamin E modestly improves cognitive function but may have a cost
Before new information emerged in 2014 regarding vitamin E and dementia, the best data were from a 1997 study16 that randomized patients with moderate dementia to either daily vitamin E 2,000 IU, the monoamine oxidase inhibitor selegiline 10 mg, both, or placebo for 2 years. No benefit of treatment for cognitive function was found. However, after adjusting for the baseline Mini-Mental State Examination score, the investigators found that either treatment was associated with a delay of about 7 months in the primary outcome (death, institutionalization, loss of activities of daily living, or severe dementia).
Unfortunately, selegiline is often poorly tolerated, causing dyskinesia in more than 10% of patients, nausea in 20%, and confusion, hallucinations, and syncope. Although vitamin E is better tolerated, in high doses it can cause fatigue, headache, and bleeding, with increased risk of hemorrhagic stroke. Studies conflict as to whether it increases the risk of death from any cause.17,18
Dysken et al,19 in a study reported in 2014, randomized 613 patients with mild to moderate Alzheimer disease, all of whom were taking an acetylcholinesterase inhibitor, to either daily vitamin E 2,000 IU, memantine 20 mg, both, or placebo. The primary outcome measure was an activities of daily living score (0–78, higher being better), which included the ability to perform such tasks as dressing oneself. Each task was scored from 0 (totally dependent on help) to 4 (able to perform completely independently).
Scores fell in both groups over the mean 2.7 years of the study, but the decrease was slightly slower in the vitamin E group: 3 points less at the end of the study compared with placebo. The groups taking memantine, vitamin E, or both did not differ significantly from one another. No significant differences were found in the secondary outcome of cognitive, neuropsychiatric, functional, and caregiver measures.
Based on the 1997 study, vitamin E may defer the time to important clinical outcomes by 7.5 months over a 2-year period in patients with moderate dementia. Based on the 2014 study, vitamin E may preserve half an activity of daily living over 2.7 years in patients with mild to moderate dementia. On the other hand, high doses of vitamin E may increase the risk of bleeding and falling, and whether they increase the risk of death is unclear.
Antidepressants for behavior issues
Other common problems in patients with major neurocognitive disorders include disturbed perception, thought content, mood, and behavior, collectively called behavioral and psychological symptoms of dementia. No known nondrug intervention is consistently effective for these problems, and no drug approved by the US Food and Drug Administration (FDA), except for a fixed-dose combination of dextromethorphan and quinidine, addresses any specific symptom.
Porsteinsson et al20 randomized 186 patients with Alzheimer disease and agitation to a psychological intervention plus either the selective serotonin reuptake inhibitor citalopram (titrated from 10 to 30 mg per day based on response and tolerability) or placebo. Agitation was reduced with citalopram compared with placebo, based on the agitation subscale of the Neurobehavioral Rating Scale.
Of those taking citalopram, 40% were much or very much improved, compared with 26% of those taking placebo. These results are comparable to or better than those with antipsychotic drugs, which should be avoided for treating dementia-related psychosis in elderly patients because of black-box warnings.
No differences were found in activities of daily living. An interesting finding, not seen in other studies, is that the Mini-Mental Status Examination score declined by 1 point in the treatment group vs no change in the placebo group (P = .03).
Prolonged QTc was found in 12.5% in the citalopram group vs 4.3% in the placebo group (P = .01). The FDA issued a warning in 2012 of a dose-dependent effect of citalopram on QTc and recommended a maximum dose of 20 mg for those over age 60; for “poor metabolizers” of cytochrome P450 2C19 (CYP 2C19); and for those taking medications that inhibit CYP 2C19, including proton pump inhibitors, cimetidine, fluvoxamine, fluoxetine, indomethacin, ketoconazole, modafinil, and probenecid. The United Kingdom has extended this warning to escitalopram. Unfortunately, in the Porsteinsson study, nearly 80% of the treatment group received the 30-mg dose and only 15% received the 20-mg dose, which provided insufficient data for independent analysis.
Possibly, citalopram cannot be administered in a dosage sufficient to produce the benefits seen in the study. Using escitalopram may also be risky. Based on this study, it would be prudent to monitor QTc when using these drugs.
Dextromethorphan and quinidine
A fixed-dose combination of dextromethorphan and quinidine (Nuedexta) was recently approved by the FDA for treatment of pseudobulbar affect in individuals with stroke, traumatic brain injury, or dementia. Pseudobulbar affect has been defined as a condition of contextually inappropriate or exaggerated emotional expression that often occurs in adults with neurologic damage.
Using a 20/10-mg dose combination, a small 12-week noncomparative trial demonstrated measurable improvement in pseudobulbar symptoms after 30 days (as measured by the Center for Neurologic Study-Lability Scale).21 Though individuals enrolled in this trial appeared to tolerate this dose, additional trials still need to be conducted to more clearly determine its long-term safety and efficacy. It is not approved for dementia with agitation, but a phase 2 trial suggests a benefit compared with placebo in reducing agitation and caregiver burden.22
RISKS OF MILD COGNITIVE IMPAIRMENT
The spectrum of cognitive impairment ranges from mild cognitive impairment (MCI), in which deficits are evident on neuropsychological testing but the person maintains overall function, to the different stages of dementia (mild, moderate, and severe). MCI was documented in the Cardiovascular Health Study in 22% of adults 75 and older.23
Despite presenting with apparently normal function, elderly people with MCI have a higher risk of falls, rehospitalization, and delirium. Screening is not typically performed for MCI in primary care. No study has compared clinical outcomes after screening vs not screening for cognitive impairment (whether MCI or dementia), and the US Preventive Services Task Force maintains that there is insufficient evidence for screening.24
Unrecognized cognitive impairment affects discharge outcomes
Nazir et al,25 in a 1-year longitudinal study, compared 976 patients age 65 and older who upon admission to a public hospital were either diagnosed with cognitive impairment (defined as scoring 7 or less on the 10-question Short Portable Mental Status Questionnaire) or not. They found that 42.5% were cognitively impaired on admission. Overall, 36.5% of patients were discharged to a facility rather than home; those who were cognitively impaired, older, and sicker were more likely to be discharged to a facility.
Interestingly, among those discharged to a facility, patients with cognitive impairment were less likely to be subsequently rehospitalized or die within 30 days of hospital discharge than those without cognitive impairment. Whether this can be explained by differences in comorbidities between the groups was not explored. Those discharged home had similar rates of death and rehospitalization whether or not they were cognitively impaired.
Patel et al26 screened 720 older patients upon discharge after hospitalization for heart failure with the Mini-Cog (a 3-minute test that consists of recall of three words and the ability to draw a clock face). About a quarter of patients were diagnosed with cognitive impairment based on this test.
Among those discharged home (about two-thirds of the group overall), patients were much more likely to be rehospitalized or die within 30 days if they were cognitively impaired. Among those discharged to a facility, the rates between the two groups were similar for the first 20 days; after that, people in the cognitively impaired group were much more likely to die or be readmitted to a hospital.
Dodson et al,27 in a study of 282 hospitalized patients with heart failure (mean age 80), identified 47% as having cognitive impairment at the time of hospitalization based on a score of less than 25 on the Mini-Mental State Examination. Of those found to have mild cognitive impairment (score 21–24), only 11% had documentation of a cognitive deficit in the medical record, and 39% of those found to have moderate to severe cognitive impairment (score < 21) had documentation of it in the medical record. Those with unrecognized impairment were 1.5 times more likely to die or be rehospitalized within 6 months than those with documented impairment.
Do interventions help?
It is unclear whether developing specific interventions tailored to cognitive impairment improves outcomes.
Davis et al28 studied 125 patients hospitalized for heart failure who were identified as having mild cognitive impairment based on a Montreal Cognitive Assessment score of 17 to 25 (out of 30) points. Patients were randomly assigned to either a targeted self-care teaching intervention or usual discharge care. The intervention included education and customized instruction on self-care tasks such as managing symptoms, organizing medications, and measuring fluid and sodium intake.
Thirty days after discharge, the intervention group had greater knowledge about heart failure than the control group, but no significant difference was found in ability to care for themselves or in readmission rates.
Interventions that target the patient-caregiver dyad may have more success. A pilot project in Indiana29 that developed an integrative care model for older people with mild cognitive impairment, dementia, or depression that targeted patients as well as their caregivers found that compared with patients from area primary care clinics, their patients had lower rehospitalization rates within 30 days of discharge (11% vs 20%) and higher rates of achieving a hemoglobin A1c of less than 8% (78% vs 51%). Results of an expanded innovations demonstration project awarded by the Centers for Medicare and Medicaid Services are pending.
The following more recently published data show promise for prevention of dementia through nonpharmacologic interventions.
The FINGER trial30 (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) screened 2,654 Finnish individuals ages 60 to 77 using the Cardiovascular Risk Factors, Aging and Dementia risk tool, identifying 1,260 individuals with higher levels of cognitive impairment and randomizing them to a 2-year intervention consisting of exercise, cognitive training, and vascular risk monitoring (n = 631), or a control group provided with general health advice only (n = 629). Neuropsychological testing was conducted to measure differences between the groups, and at the end of the study, the mean Z-score difference in the total testing score between the intervention and control group was 0.22 (P = .30). This trial demonstrated that if cognitive impairment were identified, a multimodal intervention could improve or maintain cognitive function in at-risk elderly individuals.
