Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial.

IMPORTANCE: Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD. OBJECTIVE: To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers. INTERVENTIONS: Participants received either 2000 IU/d of alpha tocopherol (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152). MAIN OUTCOMES AND MEASURES: Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures. RESULTS: Data from 561 participants were analyzed (alpha tocopherol = 140, memantine = 142, combination = 139, placebo = 140), with 52 excluded because of a lack of any follow-up data. Over the mean (SD) follow-up of 2.27 (1.22) years, ADCS-ADL Inventory scores declined by 3.15 units (95% CI, 0.92 to 5.39; adjusted P = .03) less in the alpha tocopherol group compared with the placebo group. In the memantine group, these scores declined 1.98 units less (95% CI, -0.24 to 4.20; adjusted P = .40) than the placebo group's decline. This change in the alpha tocopherol group translates into a delay in clinical progression of 19% per year compared with placebo or a delay of approximately 6.2 months over the follow-up period. Caregiver time increased least in the alpha tocopherol group. All-cause mortality and safety analyses showed a difference only on the serious adverse event of "infections or infestations," with greater frequencies in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants) compared with placebo (13 events in 11 participants). CONCLUSIONS AND RELEVANCE: Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol. These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00235716.

Vitamin E and memantine in Alzheimer's disease: clinical trial methods and baseline data.

BACKGROUND: Alzheimer's disease (AD) has been associated with both oxidative stress and excessive glutamate activity. A clinical trial was designed to compare the effectiveness of (i) alpha-tocopherol, a vitamin E antioxidant; (ii) memantine (Namenda), an N-methyl-D-aspartate antagonist; (iii) their combination; and (iv) placebo in delaying clinical progression in AD. METHODS: The Veterans Affairs Cooperative Studies Program initiated a multicenter, randomized, double-blind, placebo-controlled trial in August 2007, with enrollment through March 2012 and follow-up continuing through September 2012. Participants with mild-to-moderate AD who were taking an acetylcholinesterase inhibitor were assigned randomly to 2000 IU/day of alpha-tocopherol, 20 mg/day memantine, 2000 IU/day alpha-tocopherol plus 20 mg/day memantine, or placebo. The primary outcome for the study is the Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory. Secondary outcome measures include the Mini-Mental State Examination; the Alzheimer's Disease Assessment Scale, cognitive portion; the Dependence Scale; the Neuropsychiatric Inventory; and the Caregiver Activity Survey. Patient follow-up ranged from 6 months to 4 years. RESULTS: A total of 613 participants were randomized. The majority of the patients were male (97%) and white (86%), with a mean age of 79 years. The mean Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory score at entry was 57 and the mean Mini-Mental State Examination score at entry was 21. CONCLUSION: This large multicenter trial will address the unanswered question of the long-term safety and effectiveness of alpha-tocopherol, memantine, and their combination in patients with mild-to-moderate AD taking an acetylcholinesterase inhibitor. The results are expected in early 2013.

Care coordination assisted by technology for multiethnic caregivers of persons with dementia: a pilot clinical demonstration project on caregiver burden and depression.

We evaluated a care-coordination project assisted by a screen-phone to support and educate caregivers. A total of 113 caregivers of home-dwelling veterans with dementia were recruited to the study: 72 were white, 32 were African American and nine were Hispanic. Caregivers were assessed for burden, depression, coping, quality of life, knowledge and satisfaction. None of the outcome measures changed significantly after 12 months. Forty care-recipient and caregiver dyads responded to the 12-month telephone satisfaction survey. The respondents were more satisfied with the care-coordination (90%) aspect of the programme than the education (77%) or the monitoring (50%). The pilot project suggests that care coordination aided by screen-phones may be a useful model for caregiver support in a managed-care setting. A systematic study is now required.

Older patients presenting to a county hospital ED after a fall: missed opportunities for prevention.

Little is known about the characteristics of elderly persons who present to an ED after a fall or about the nature of the care received for the fall itself. We identified elders presenting to a large urban United States ED after a fall, determined risk factors that may have contributed to the fall, and assessed the extent to which falls were addressed in the ED setting. One hundred seventeen fallers were identified. Nearly half were aged 80 years or older. After age, polypharmacy was the most common fall risk factor, followed by more than 1 contributing medical condition and cognitive impairment. Fall risk factors differed significantly for older compared with younger subgroups. More than half (57%) who had fallen were admitted. Of the remainder who fell and were discharged, more than half were scheduled for follow-up of their fall-related injury only, with no follow-up scheduled to address prevention of future falls. In summary, elders who present to an ED after having fallen have a variety of risk factors for falls that can be addressed to reduce their risk of future falls and injury; however, many may not receive such follow-up care. There must be increased awareness among ED providers of the need for a medical evaluation of a fall. Randomized trials evaluating the effect of a focused fall risk factor assessment after presentation to the ED may be warranted.

BMI and low bone mass in an elderly male nursing home population.

INTRODUCTION: Little is known about osteoporosis in institutionalized older adults. Risk factors such as low body mass index (BMI) have been investigated in female populations, but remain understudied in men. The objective of this study was to examine characteristics of older men residing in a nursing home who received bone mineral density evaluations. METHODS: 57 male Miami Veterans Affairs Medical Center (VAMC) nursing home residents were screened for osteoporosis using a peripheral dual X-ray (pDXA) technique. T-scores were categorized into three groups: normal (0 > -1); osteopenic (-1 to -2.49); osteoporotic (< -2.5). RESULTS: Average age was 76.2 years (standard deviation = 11.5; range: 48-100). T-scores indicated that 37.3% of the population was normal, 35.6% osteopenic, and 27.1% osteoporotic. 35.6% of patients had normal BMIs, 3.4% were underweight, 47.5% were overweight, and 13.6% were considered obese. There was a high prevalence of overweight and obese individuals (61.1%) in the osteopenic and osteoporotic groups. CONCLUSION: As expected, there was a high prevalence of low bone mass in our population (62%). However, overweight and obese men were more likely to have osteoporosis and osteopenia, contrary to literature and clinical knowledge. This finding may be partially explained by the prevalence of sedentary lifestyle and relative lack of weight-bearing activity in this group of men.

A statewide case-control study of spousal homicide-suicide in older persons.

OBJECTIVE: Homicide-suicides are rare relative to suicides and homicides, but these lethal events are an emerging public health concern. They have a mortality count similar to meningitis, pulmonary tuberculosis, influenza, and viral hepatitis, and the rate may be increasing in the United States, especially among older persons. The goal of this case-control study was to identify factors that differentiate older married men who commit homicide-suicide from those who commit suicide only. METHODS: A total of 20 spousal homicide-suicides involving persons age 55 years and older were ascertained in Florida between January 1, 1998 and December 31, 1999 from medical examiner records. Two suicide controls were matched to each homicide-suicide perpetrator by age, race, marital status, method of death, and medical examiner district. Perpetrator groups were compared on sociodemographic characteristics, medical variables, and autopsy findings. RESULTS: Homicide-suicide perpetrators displayed significantly more domestic violence or were caregivers for their wives, in contrast to suicide perpetrators, who had health problems and were receiving care from their spouses. Both groups of perpetrators had reported depressed mood, and there were no differences in sociodemographic factors. CONCLUSIONS: Depression plays a significant role in both homicide-suicide and suicide, but the associated factors are different: we see caregiving strain in perpetrators of homicide-suicide, and living with physical health disorders as a care-recipient in men who commit suicide. Marital conflict is a significant factor in some spousal homicide-suicides.

Antecedents of euthanasia and suicide among older women.

OBJECTIVES: To identify the characteristics of older women who sought Jack Kevorkian's assistance in dying and to compare them with those of an age-matched sample who committed suicide. METHOD: This retrospective case-control study compared all 18 women age 55 and older who died with the assistance of Jack Kevorkian and whose deaths were investigated in Oakland County, Michigan from 1995 to 1997 with all 15 women age 55 and older who committed suicide in the same county during the same time period. We coded 203 variables in 7 domains from medical examiner files, including autopsy findings. RESULTS: Significantly more of Kevorkian's cases had amyotrophic lateral sclerosis or multiple sclerosis (p = .018), a recent decline in health (p = .031), or inadequately controlled pain (p = .041). Women who committed suicide had more prevalent chronic illnesses and were more likely to have been diagnosed with clinically significant depression or other psychiatric disorders (p = .023). Both groups were significantly less likely to be married (p < .001) and more likely to be divorced (p < .001) than US Census data would predict. CONCLUSIONS: The different vulnerabilities of older women who want to die and either commit suicide or seek assistance deserve continued careful research. Poorly controlled pain was a factor in seeking assistance in dying, and depression and psychiatric disorders characterized older women who committed suicide in our study. Not having a spouse may increase isolation and reinforce the hopelessness of women who are living with catastrophic illness.

A newspaper surveillance study of homicide-suicide in the United States.

The objective of this study was to identify the number and subtypes of homicide-suicides in the United States by age group and state over a 3-year period from 1997 through 1999. A total of 673 homicide-suicides, including 674 perpetrators and 779 victims, were identified from Internet searches of 191 national newspapers, and they were classified according to a modified Hanzlick-Koponen typology. One quarter of the homicide-suicides were perpetrated by persons 55 years or older, and 77% were spousal/consortial, higher than the 57% observed in the younger age group; 11% of the older homicide-suicides were familial, compared with 16% in the younger age group. Whereas only 3% of older homicide-suicides were infanticide/pedicide, 16% of the younger homicide-suicides involved parents killing their children. Forty-five states, including the District of Columbia, reported a homicide-suicide during the 3-year period, and they occurred most frequently in Florida (163), California (98), Texas (36), and New York (35). Newspaper surveillance is useful to identify where homicide-suicides are occurring most frequently, but they are underestimates of the true prevalence. However, the number of incidents detected is large enough that the cases detected may be a fairly representative sample.