Caregiver Experience of Tele-dementia Care for Older Veterans.

BACKGROUND: For the 5 million persons living with dementia (PLWD) in the USA, telemedicine may improve access to specialty care from their homes. OBJECTIVE: To elicit informal caregiver perceptions of tele-dementia care provided during COVID-19. DESIGN: Qualitative, observational study using grounded theory. PARTICIPANTS: Informal caregivers aged 18 + who cared for an older adult who received tele-dementia services at two major VA healthcare systems participated in 30-60-min semi-structured telephone interviews. INTERVENTIONS: Interviews were designed using Fortney's Access to Care model. MAIN MEASURES: Thirty caregivers (mean age = 67, SD = 12, 87% women) were interviewed. KEY RESULTS: Five major themes were (1) Tele-dementia care avoids routine disruption and pre-visit stress; (2) Transportation barriers to in-person visits include not only travel logistics but navigating the sequelae of dementia and comorbid medical conditions. These include cognitive, behavioral, physical, and emotional challenges such as balance issues, incontinence, and agitation in traffic; (3) Tele-dementia care saves time and money and improves access to specialists; (4) Tele-dementia facilitated communication between caregiver and provider without hindering communication between PLWD and provider; and (5) Caregivers described ideal future dementia care as a combination of virtual and in-person modalities with in-home help, financial and medical support, and dementia-sensitive caregiver access. Caregivers interviewed saved 2.6 h ± 1.5 h (range: 0.5 to 6 h) of travel time. Multiple caregivers described disruption of routines as difficult in PLWD and appreciated the limited preparation and immediate return to routine post telemedicine visit as positives. CONCLUSIONS: Caregivers found tele-dementia care convenient, comfortable, stress reducing, timesaving, and highly satisfactory. Caregivers would prefer a combination of in-person and telemedicine visits, with an opportunity to communicate with providers privately. This intervention prioritizes care for older Veterans with dementia who have high care needs and are at higher risk for hospitalization than their same age counterparts without dementia.

Plasma Citrate and Succinate Are Associated With Neurocognitive Impairment in Older People With HIV.

BACKGROUND: Neurocognitive impairment (NCI) is associated with monocyte activation in people with HIV (PWH). Activated monocytes increase glycolysis, reduce oxidative phosphorylation, and accumulate citrate and succinate, tricarboxylic acid (TCA) cycle metabolites that promote inflammation-this metabolic shift may contribute to NCI and slowed gait speed in PWH. METHODS: Plasma citrate and succinate were assayed by liquid chromatography-mass spectrometry from 957 participants upon entry to a multicenter, prospective cohort of older PWH. Logistic, linear, and mixed-effects linear regression models were used to examine associations between entry/baseline TCA cycle metabolites and cross-sectional and longitudinal NCI, neuropsychological test scores (NPZ-4), and gait speed. RESULTS: Median age was 51 (range 40-78) years. Each 1 standard deviation (SD) citrate increment was associated with 1.18 higher odds of prevalent NCI at baseline (P = .03), 0.07 SD lower time-updated NPZ-4 score (P = .01), and 0.02 m/s slower time-updated gait speed (P < .0001). Age accentuated these effects. In the oldest age-quartile, higher citrate was associated with 1.64 higher odds of prevalent NCI, 0.17 SD lower NPZ-4, and 0.04 m/s slower gait speed (P ≤ .01 for each). Similar associations were apparent with succinate in the oldest age-quintile, but not with gait speed. In participants without NCI at entry, higher citrate predicted a faster rate of neurocognitive decline. CONCLUSIONS: Higher plasma citrate and succinate are associated with worse cross-sectional and longitudinal measures of neurocognitive function and gait speed that are age-dependent, supporting the importance of altered bioenergetic metabolism in the pathogenesis of NCI in older PWH.

Impact of apolipoprotein E genotypes on vitamin E and memantine treatment outcomes in Alzheimer's disease.

INTRODUCTION: Because apolipoprotein E (APOE) genotypes are known risk factors for Alzheimer's disease (AD), they have been measured in clinical trial participants to determine their effect on treatment outcome. METHODS: We determined APOE genotypes in a subset of subjects (N = 415) who participated in a randomized controlled trial of vitamin E and memantine in 613 veterans with mild-to-moderate AD. RESULTS: Similar to the primary study, substudy participants receiving vitamin E also had slower functional decline than those receiving placebo. Overall, there was no difference in the rate of functional decline between APOE ε4 allele carriers and noncarriers. A significant interaction was observed between treatment and the APOE genotype on AD progression: ε4 carriers declined faster than noncarriers in the vitamin E plus memantine treatment arm. DISCUSSION: APOE genotypes may modulate AD treatment response and should be included in the design of future randomized controlled trials.

Neuropsychiatric Symptoms and Caregiver Burden in Individuals With Alzheimer's Disease: The TEAM-AD VA Cooperative Study.

OBJECTIVES: To assess the prevalence of neuropsychiatric symptoms (NPS) in mild-to-moderate Alzheimer disease (AD) and their association with caregiver burden. METHODS: Secondary analyses of baseline data from the Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD) (N=613). Neuropsychiatric Inventory were used to measure severity of NPS and caregiver activity survey to measure caregiver burden. RESULTS: A total of 87% of patients displayed at least 1 NPS; 70% displayed clinically meaningful NPS. The most common symptoms were apathy (47%), irritability (44%), agitation (42%), and depression (40%). Those with moderate AD had more severe NPS than those with mild AD ( P = .03). Neuropsychiatric symptoms were significantly associated with caregiver time after adjusting for age, education, cognitive function, and comorbidity ( P-value < .0001) with every point increase in NPS associated with a 10-minute increase in caregiver time. CONCLUSION: Neuropsychiatric symptoms were prevalent in both mild and moderate AD, even in patients receiving treatment with an acetylcholinesterase inhibitors, and were more severe in moderate AD and associated with greater caregiver time.

Measuring informed consent capacity in an Alzheimer's disease clinical trial.

INTRODUCTION: Accurately and efficiently determining a participant's capacity to consent to research is critically important to protect the rights of patients with Alzheimer's disease (AD). METHODS: Understanding of the informed consent document was assessed in 613 community-dwelling patients with mild-to-moderate AD enrolled in a randomized, placebo-controlled trial. Associations were examined between clinically determined capacity to consent and (1) patient demographics and clinical characteristics and (2) the Informed Consent Questionnaire (ICQ), an objective measurement of a participant's factual understanding and perceived understanding. RESULTS: A total of 453 (74%) participants were determined to have capacity to consent by clinical judgment. ICQ perceived understanding, race, measures of cognitive function, and caregiver time were all significantly associated with the determination of capacity in multivariate analyses. DISCUSSION: We found a significant association between capacity and disease severity level, caregiver time, race, and ICQ perceived understanding.

Racial Difference in Response to Vitamin D Supplementation.

UNLABELLED: This manuscript is the result of work supported by the use of resources and facilities at the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, specifically, the Geriatric Research Education and Clinical Center (GRECC). BACKGROUND: Deficiency in 25-hydroxyvitamin D (25[OH]D) is common, especially in the elderly and African Americans (AA). While 25(OH) D deficiency is associated with multiple negative health outcomes, current recommendations for supplementation of this deficiency may be insufficient. OBJECTIVE: To determine the prevalence of 25(OH)D deficiency, the extent of vitamin D supplementation, and the effect of supplementation on 25(OH) D levels in an elderly Veteran population. The study also focused specifically on the role of race in the risk for 25(OH)D deficiency and in the response to vitamin D supplementation. METHODS: A retrospective chart review was conducted of information including 25(OH)D serum levels pre and post-supplementation, race, and vitamin D supplementation. Subjects were community-dwelling Veterans (≥60years) followed by a VA geriatric clinic. A total of 234 charts were reviewed (124 Caucasian, 78 AA, 32 other/unknown race). Information collected through the chart review was analyzed by comparing the means of 25(OH)D levels pre and post-supplementation across races and across times. RESULTS: At Baseline 206 subjects (88%) were 25(OH)D deficient (<32ng/ml). While 80.6% of them were supplemented, only 10.24% (17 of 166) achieved normal 25(OH)D serum levels. AAs (n=78) had significantly lower Baseline levels compared to Caucasians (n=124) and differences were consistent across time. Fewer AAs than Caucasians increased to normal (AA:6.3%; Caucasian:12.8%). CONCLUSIONS: Conservative oral vitamin D supplementation is largely ineffective at achieving therapeutic serum levels, especially for AAs. Future research is needed to focus on individualized supplementation strategies and targeted risk factors such as race.

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.

General principles of hypertension management in the elderly.

The geriatric population is growing in number and along with it, the prevalence of hypertension (HTN). The elderly have a unique set of characteristics that must be taken into account when treating this condition. Not only is it widespread, but its consequences, mainly cardiovascular and cerebrovascular, are devastating. Because the elderly have multiple comorbid concomitant conditions, the practitioner must be cognizant of polypharmacy and resistant HTN and prescribe in a safe fashion conducive to compliance and efficacy. Treatment in even the oldest old is indicated. Function and quality of life should be the driving principles when managing the elderly, be they in the ambulatory or long-term care setting.

Enhanced hypoprothrombinemia with warfarin due to azithromycin.

OBJECTIVE: To report a case of probable azithromycin-warfarin drug interaction with enhanced hypoprothrombinemic effect of warfarin. CASE SUMMARY: An 83-year-old African American man stabilized on warfarin therapy (10 mg on Wednesdays, 7.5 mg on other days) developed a prolonged prothrombin time one day after starting azithromycin 500 mg. The elevated prothrombin time normalized 3 days after azithromycin was discontinued. After the initial increase in the international normalized ratio, the absence of any significant confounding factors affecting the anticoagulant effect of warfarin in our patient and the numerous reports of such interactions indicate that an interaction between azithromycin and warfarin may have been responsible for the elevated prothrombin time seen in this patient. An objective causality assessment revealed that the adverse event was probably related to the combination of these drugs. DISCUSSION: Azithromycin, unlike erythromycin and clarithromycin, is not known to inhibit the cytochrome P450 enzyme system and is presumed to be the macrolide of choice in patients already on warfarin. However, previously reported cases of azithromycin-warfarin interactions support the possibility that azithromycin does interact with warfarin, although the exact mechanism is not understood. CONCLUSIONS: Azithromycin may interact with warfarin and enhance its hypoprothrombinemic effects. This effect may be delayed for 4-8 days after a course of azithromycin has been completed. Periodic monitoring of the prothrombin time is recommended when using azithromycin in patients taking warfarin.

Lactic acidemia associated with metformin.

OBJECTIVE: To report 2 cases of lactic acidemia associated with the use of metformin in patients with normal renal function. CASE SUMMARY: An 82-year-old African American man and a 76-year-old white man developed an elevated serum lactic acid concentration a few weeks after initiation of metformin therapy for type 2 diabetes. After the patients discontinued metformin, the serum lactic acid concentration normalized in both cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of metformin. DISCUSSION: Metformin interferes with the production and elimination of lactic acid by a variety of mechanisms that are not well understood. Few systematic data are available on changes in plasma lactic acid concentrations in patients with type 2 diabetes and normal renal function. Clinical significance of a high serum lactic acid concentration needs clarification. CONCLUSIONS: Metformin therapy can be associated with subclinical elevation of lactic acid concentration in the absence of renal insufficiency or other contraindications to using this agent in patients with type 2 diabetes. Periodic monitoring of basic metabolic panels may prevent this potentially serious complication of metformin therapy.