Cognitive Effects of Aerobic Exercise in Alzheimer's Disease: A Pilot Randomized Controlled Trial.

BACKGROUND: Aerobic exercise has shown inconsistent cognitive effects in older adults with Alzheimer's disease (AD) dementia. OBJECTIVE: To examine the immediate and longitudinal effects of 6-month cycling on cognition in older adults with AD dementia. METHODS: This randomized controlled trial randomized 96 participants (64 to cycling and 32 to stretching for six months) and followed them for another six months. The intervention was supervised, moderate-intensity cycling for 20-50 minutes, 3 times a week for six months. The control was light-intensity stretching. Cognition was assessed at baseline, 3, 6, 9, and 12 months using the AD Assessment Scale-Cognition (ADAS-Cog). Discrete cognitive domains were measured using the AD Uniform Data Set battery. RESULTS: The participants were 77.4±6.8 years old with 15.6±2.9 years of education, and 55% were male. The 6-month change in ADAS-Cog was 1.0±4.6 (cycling) and 0.1±4.1 (stretching), which were both significantly less than the natural 3.2±6.3-point increase observed naturally with disease progression. The 12-month change was 2.4±5.2 (cycling) and 2.2±5.7 (control). ADAS-Cog did not differ between groups at 6 (p = 0.386) and 12 months (p = 0.856). There were no differences in the 12-month rate of change in ADAS-Cog (0.192 versus 0.197, p = 0.967), memory (-0.012 versus -0.019, p = 0.373), executive function (-0.020 versus -0.012, p = 0.383), attention (-0.035 versus -0.033, p = 0.908), or language (-0.028 versus -0.026, p = 0.756). CONCLUSION: Exercise may reduce decline in global cognition in older adults with mild-to-moderate AD dementia. Aerobic exercise did not show superior cognitive effects to stretching in our pilot trial, possibly due to the lack of power.

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.

Intermediate- and Long-Term Cognitive Outcomes After Cardiovascular Procedures in Older Adults: A Systematic Review.

BACKGROUND: Risks for intermediate- and long-term cognitive impairment after cardiovascular procedures in older adults are poorly understood. PURPOSE: To summarize evidence about cognitive outcomes in adults aged 65 years or older at least 3 months after coronary or carotid revascularization, cardiac valve procedures, or ablation for atrial fibrillation. DATA SOURCES: MEDLINE, Cochrane, and Scopus databases from 1990 to January 2015; ClinicalTrials.gov; and bibliographies of reviews and eligible studies. STUDY SELECTION: English-language trials and prospective cohort studies. DATA EXTRACTION: One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and strength of evidence (SOE). DATA SYNTHESIS: 17 trials and 4 cohort studies were included; 80% of patients were men, and mean age was 68 years. Cognitive function did not differ after the procedure between on- and off-pump coronary artery bypass grafting (CABG) (n = 6; low SOE), hypothermic and normothermic CABG (n = 3; moderate to low SOE), or CABG and medical management (n = 1; insufficient SOE). One trial reported lower risk for incident cognitive impairment with minimal versus conventional extracorporeal CABG (risk ratio, 0.34 [95% CI, 0.16 to 0.73]; low SOE). Two trials found no difference between surgical carotid revascularization and carotid stenting or angioplasty (low and insufficient SOE, respectively). One cohort study reported increased cognitive decline after transcatheter versus surgical aortic valve replacement but had large selection and outcome measurement biases (insufficient SOE). LIMITATIONS: Mostly low to insufficient SOE; no pertinent data for ablation; limited generalizability to the most elderly patients, women, and persons with substantial baseline cognitive impairment; and possible selective reporting and publication bias. CONCLUSION: Intermediate- and long-term cognitive impairment in older adults attributable to the studied cardiovascular procedures may be uncommon. Nevertheless, clinicians counseling patients before these procedures should discuss the uncertainty in their risk for adverse cognitive outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Potentially suboptimal prescribing for older veteran nursing home patients with dementia.

BACKGROUND: Nursing home patients with dementia may be more likely to suffer adverse drug events from suboptimal prescribing. Previous studies have not used national samples, nor have they examined multiple types of suboptimal prescribing by dementia severity. OBJECTIVE: To examine the prevalence of and factors associated with potentially suboptimal prescribing in older veteran nursing home patients with dementia. METHODS: This is a retrospective descriptive study of 1303 veterans 65 years or older admitted between January 1, 2004, and June 30, 2005, with dementia for long stays (90+ days) to 133 Veterans Affairs Community Living Centers. Dementia severity was determined by the Cognitive Performance Scale and functional status dependences. RESULTS: Overall, 70.2% with mild-moderate dementia (n = 1076) had underuse because they did not receive an acetylcholinesterase inhibitor (AChEI), and 27.2% had evidence of inappropriate use because of a drug-disease or drug-drug-disease interaction. Of the 227 with severe dementia, 36.1% had overuse by receiving an AChEI or lipid-lowering or other agents, and 25.1% had evidence of inappropriate use as a result of a drug-disease or drug-drug interaction. Multinomial logistic regression analyses among those with mild to moderate dementia identified that living in the South versus other regions was the single factor associated with all 3 types of suboptimal prescribing. In those with severe dementia, antipsychotic use was associated with all 3 suboptimal prescribing types. CONCLUSIONS: Potentially suboptimal prescribing was common in older veteran nursing home patients with dementia. Clinicians should develop a heightened awareness of these problems. Future studies should examine associations between potentially suboptimal prescribing and health outcomes in patients with dementia.

Impact of 6-month aerobic exercise on Alzheimer's symptoms.

Little is known about how aerobic exercise affects Alzheimer's disease (AD). The purpose of this pilot study was to test the impact of 6-month cycling on AD symptoms in community-dwelling older adults with mild-to-moderate AD, using a single-group, repeated-measures design (n = 26). AD symptoms were measured with the AD Assessment Scale-Cognitive (ADAS-Cog), Disability in AD (DAD), and Neuropsychiatric Inventory-Caregiver (NPI-Q) scales at baseline, 3 and 6 months. Data were analyzed using mixed linear models. The ADAS-Cog, DAD, and NPI-Q severity scores remained unchanged over the 6-month period, while caregiver distress decreased 40% (p < .05). We conclude that aerobic exercise may reduce AD symptoms and appears effective in decreasing caregiver distress. Further randomized controlled trials are needed to examine the effects of aerobic exercise in AD.

Effects of aerobic exercise on cognition and hippocampal volume in Alzheimer's disease: study protocol of a randomized controlled trial (The FIT-AD trial).

BACKGROUND: Alzheimer's disease, a global public health issue, accounts for 60 to 80% of all dementias. Alzheimer's disease primarily causes cognitive impairment and drugs have only modest short-term effects, highlighting a pressing need to develop effective interventions. Aerobic exercise holds promise for treating cognitive impairment in Alzheimer's disease through biologically sound mechanisms. Nonetheless, aerobic exercise studies in Alzheimer's disease are limited with mixed findings. METHODS/DESIGN: This pilot randomized controlled trial will investigate the effects of a 6-month, individualized, moderate-intensity cycling intervention (20 to 50 minutes per session, 3 times a week) on cognition and hippocampal volume in community-dwelling older adults with mild-to-moderate Alzheimer's disease. The specific aims are to: 1) determine the immediate effect of the cycling intervention on cognition in Alzheimer's disease; 2) examine if the cycling intervention slows cognitive decline in Alzheimer's disease from baseline to 12 months; and 3) assess the effect of aerobic exercise on hippocampal volume over 12 months. Ninety subjects will be randomized on a 2:1 allocation ratio to cycling or attention control (low-intensity stretching) and followed for another 6 months. Allocations will be concealed to all investigators and outcome assessors will be blinded to group assignments and previous data. Cognition will be measured by the Alzheimer's disease Assessment Scale-Cognition at baseline before randomization and at 3, 6, 9, and 12 months. Hippocampal volume will be measured by magnetic resonance imaging at baseline and 6 and 12 months. The sample size of 90 will give 80% power to detect a 2.5-point difference in within-group changes in the Alzheimer's disease Assessment Scale-Cognition at 6 months for the cycling group. DISCUSSION: Findings from this study will address the critical gap of exercise efficacy in Alzheimer's disease and use of magnetic resonance imaging as an outcome measure in clinical trials. This study will provide a potential treatment that may increase physical function and quality of life and curb the prohibitive costs for the growing dementia population. TRIAL REGISTRATION: Primary registration: (NCT01954550; date of registration: 20 September 2013). Secondary registration: (NCT01954550; date of registration: 1 October 2013).

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.

Affecting cognition and quality of life via aerobic exercise in Alzheimer's disease.

Aerobic exercise is a promising behavioral therapy for Alzheimer's disease (AD), yet few studies have investigated the effect of aerobic exercise on cognition in AD. The purpose of this pilot study was to examine the effect of 6-month aerobic exercise on the change in executive function, global cognition, quality of life (QOL), and depression in community-dwelling older adults with mild to moderate AD. A single group, repeated measures design with outcomes measured at baseline, 3 months, and 6 months was used. Results show that there were no significant changes in any measures except for depression (p = .026). There was a trend toward improvement in executive function and QOL with moderate effect sizes (ESs) and a trend toward deterioration in global cognition with moderate to large ESs. Randomized controlled trials are needed to evaluate the therapeutic effect of aerobic exercise in older adults with AD.

Calcium and vitamin D supplementation and cognitive impairment in the women's health initiative.

OBJECTIVES: To examine the effects of vitamin D and calcium on cognitive outcomes in elderly women. DESIGN: Post hoc analysis of a randomized double-blind placebo-controlled trial. SETTING: Forty Women's Health Initiative (WHI) clinical centers across the United States. PARTICIPANTS: Four thousand one hundred forty-three women aged 65 and older without probable dementia at baseline who participated in the WHI Calcium and Vitamin D Trial and the WHI Memory Study. INTERVENTION: Two thousand thirty-four women were randomized to receive 1,000 mg of calcium carbonate combined with 400 IU of vitamin D(3) (treatment) and 2,109 to placebo. MEASUREMENTS: Primary: classifications of probable dementia or mild cognitive impairment (MCI) based on a four-phase protocol that included central adjudication. Secondary: global cognitive function and individual cognitive subtests. RESULTS: Mean age of participants was 71. During a mean follow-up of 7.8 years, 39 participants in the treatment group and 37 in the placebo group developed incident dementia (hazard ratio (HR) = 1.11, 95% confidence interval (CI) = 0.71-1.74, P = .64). Likewise, 98 treatment participants and 108 placebo participants developed incident MCI (HR = 0.95, 95% CI = 0.72-1.25, P = .72). There were no significant differences in incident dementia or MCI or in global or domain-specific cognitive function between groups. CONCLUSION: There was no association between treatment assignment and incident cognitive impairment. Further studies are needed to investigate the effects of vitamin D and calcium separately, on men, in other age and ethnic groups, and with other doses.

Use of antipsychotics among older residents in VA nursing homes.

BACKGROUND: Antipsychotic medications are commonly prescribed to nursing home residents despite their well-established adverse event profiles. Because little is known about their use in Veterans Affairs (VA) nursing homes [ie, Community Living Centers (CLCs)], we assessed the prevalence and risk factors for antipsychotic use in older residents of VA CLCs. METHODS: This cross-sectional study included 3692 Veterans age 65 or older who were admitted between January 2004 and June 2005 to one of 133 VA CLCs and had a stay of ≥90 days. We used VA Pharmacy Benefits Management data to examine antipsychotic use and VA Medical SAS datasets and the Minimum Data Set to identify evidence-based indications for antipsychotic use (eg, schizophrenia, dementia with psychosis). We used multivariable logistic regression and generalized estimating equations to identify factors independently associated with antipsychotic receipt. RESULTS: Overall, 948/3692(25.7%) residents received an antipsychotic, of which 59.3% had an evidence-based indication for use. Residents with aggressive behavior [odds ratio (OR)=2.74, 95% confidence interval (CI), 2.04-3.67] and polypharmacy (9+ drugs; OR=1.84, 95% CI, 1.41-2.40) were more likely to receive antipsychotics, as were users of antidepressants (OR=1.37, 95% CI, 1.14-1.66), anxiolytic/hypnotics (OR=2.30, 95% CI, 1.64-3.23), or drugs for dementia (OR=1.52, 95% CI, 1.21-1.92). Those residing in Alzheimer/dementia special care units were also more likely to receive an antipsychotic (OR=1.66, 95% CI, 1.26-2.21). Veterans with dementia but no documented psychosis were as likely as those with an evidence-based indication to receive an antipsychotic (OR=1.10, 95% CI, 0.82-1.47). CONCLUSIONS: Antipsychotic use is common among VA nursing home residents aged 65 and older, including those without a documented evidence-based indication for use. Further quality improvement efforts are needed to reduce potentially inappropriate antipsychotic prescribing.

Finding dementia in primary care: the results of a clinical demonstration project.

OBJECTIVES: To assess the effect of screening on diagnosing cognitive impairment. DESIGN: Quality improvement initiative. SETTING: Seven Veterans Affairs Medical Centers. PARTICIPANTS: Veterans aged 70 or older without a prior diagnosis of cognitive impairment. MEASUREMENTS: Veterans failing a brief cognitive screen (Mini-Cog score <4/5) at a routine primary care visit were offered a further, comprehensive evaluation with an advance practice registered nurse trained in dementia care and integrated into the primary care clinic. Veterans completing the evaluation were reviewed in a consensus conference and assigned a diagnosis of dementia; cognitive impairment, no dementia; or no cognitive impairment. Total numbers of screens, associated scores (0-5), and the consensus diagnoses were tallied. New cognitive impairment diagnoses were also tracked for veterans who passed the screen but requested further evaluation, failed but declined further evaluation, or were not screened. Primary care provider satisfaction with the program also was assessed. RESULTS: Of 8,342 veterans offered screening, 8,063 (97%) accepted, 2,081 (26%) failed the screen, 580 (28%) agreed to further evaluation, and 540 (93%) were diagnosed with cognitive impairment, including 432 (75%) with dementia. For screen passes requesting further evaluation, 87% (103/118) had cognitive impairment, including 70% (82/118) with dementia. Screen failures declining further evaluation had 17% (259/1,501) incident cognitive impairment diagnosed through standard care, bringing the total newly documented cognitive impairment in all screens to 11% (902/8,063), versus 4% (1,242/28,349) in similar clinics without this program. Eighty-two percent of primary care providers in clinics with this program agreed that it provided a useful service. CONCLUSION: Screening combined with offering further evaluation increased new diagnoses of cognitive impairment in older veterans two to three times. Veterans accepted screening well, and providers found the program useful.

Discontinuation of acetylcholinesterase inhibitor treatment in the nursing home.

BACKGROUND: Dementia treatment guidelines are not consistent in determining how long to continue acetylcholinesterase inhibitor (AChEI) treatment in patients with Alzheimer's disease. OBJECTIVE: Our aim was to examine reasons for AChEI discontinuation in a nursing home to better understand how practitioners actually decide when to stop treatment. METHODS: A retrospective chart review was done on 107 deceased nursing home veterans who had been taking an AChEI to determine the time between discontinuation and death. RESULTS: In the majority of residents (n = 67; 63%), the AChEI was continued into the week preceding death. Reasons for discontinuation were dying or death (n = 56; 52%), admission to hospice (n = 13; 12.2%), and admission to the nursing home (n = 5; 4.7%). Admission to hospice (P = 0.01), hospice length of stay (P = 0.0004), and length of stay at Minnesota Veterans Home (P = 0.02) were significantly associated with discontinuation of AchEI before the last week of life. CONCLUSION: Our study showed that residents were significantly more likely to have their AChEI discontinued if they were either admitted to hospice, stayed longer in hospice, or stayed longer in the nursing home. In addition, the majority of residents continued AChEI treatment until sometime during the week before death occurred.

Potential underuse, overuse, and inappropriate use of antidepressants in older veteran nursing home residents.

OBJECTIVES: To examine prevalence and resident- and site-level factors associated with potential underuse, overuse, and inappropriate use of antidepressants in older Veterans Affairs (VA) Community Living Center (CLC) residents. DESIGN: Longitudinal study. SETTING: One hundred thirty-three VA CLCs. PARTICIPANTS: Three thousand six hundred ninety-two veterans aged 65 and older admitted between January 1, 2004, and June 3, 2005, with long stays (≥ 90 days). MEASUREMENTS: Prevalence of potential underuse, inappropriate use, and overuse of antidepressants in residents with and without depression (as documented according to International Classification of Diseases, Ninth Revision, Clinical Modification, codes or Depression Rating Scale). RESULTS: Selective serotonin reuptake inhibitors were the most commonly prescribed antidepressant. Of the 877 residents with depression, 25.4% did not receive an antidepressant, suggesting potential underuse. Of residents with depression who received antidepressants, 57.5% had potential inappropriate use due primarily to problems seen with drug-drug and drug-disease interactions. Of the 2,815 residents who did not have depression, 1,190 (42.3%) were prescribed one or more antidepressants; only 48 (4.0%) of these had a Food and Drug Administration-approved labeled indication, suggesting potential overuse. Overall, only 17.6% of antidepressant use was appropriate (324/1,844). The only consistent resident factor associated with potential underuse and overuse use was taking an antipsychotic without evidence of schizophrenia (underuse: adjusted relative risk ratio (ARRR)=0.56, 95% confidence interval (CI)=0.33-0.94; overuse: adjusted odds ratio=1.52, 95% CI=1.21-1.91). Having moderate to severe pain (ARRR=1.54, 95% CI=1.08-2.20) and the prescribing of an anxiolytic or hypnotic (ARRR=1.33, 95% CI=1.02-1.74) increased the risk of potential inappropriate antidepressant use. CONCLUSION: Potential problems with the use of antidepressants were frequently observed in older U.S. veteran CLC residents. Future studies are needed to examine the true risks and benefits of antidepressant use in CLC and non-VA nursing homes.

Aerobic training for older men with Alzheimer's disease: individual examples of progression.

Little is known about cardiorespiratory fitness and aerobic exercise training in older adults with Alzheimer's disease (AD). The purposes of this article are to describe the change in cardiorespiratory fitness after 2 months of aerobic training and the feasibility of aerobic training in 4 men with moderate-to-severe AD. A one-group, pretest-posttest test design was used to measure cardiorespiratory fitness using symptom limited, graded cycle ergometer testing. In exit interviews, participants and spouses identified exercise facilitators and barriers. The results show that cardiorespiratory fitness increased in 2 participants with moderate AD but decreased in 2 with severe AD. Participants showed great variability in exercise progression and doses actually delivered. In conclusion, older men with moderate-to-severe AD can engage in aerobic training. Two months might be better used as the adaptive period for longer duration aerobic training, such as a 6-month program. Suggestions and implications for future exercise research in AD are detailed.

Fluorodeoxyglucose positron emission tomography of mild cognitive impairment with clinical follow-up at 3 years.

BACKGROUND: Alzheimer's disease (AD) is the most common dementing illness. Development of effective treatments directed at AD requires an early diagnosis. Mild cognitive impairment (MCI) often heralds AD. Thus, characterizing MCI is fundamental to the early diagnosis of AD. METHODS: 19 MCI patients referred from a memory loss clinic and 27 healthy subjects, all followed up for 3 years. Metabolism scans (MCI minus controls) were compared voxel-wise after anatomic normalization and were examined both visually and with a computerized classifier. RESULTS: Agreement between raters as to whether the individual scans were normal or abnormal was high. Agreement between raters of the eventual clinical diagnosis and baseline metabolic pattern was poor. A computerized classifier was unsuccessful at classifying MCI from normal; however, its performance improved when using only prototypic AD-like MCI scans, indicating the classifier worked well when shared patterns existed in the data. Outcomes on follow-up were nine of 19 AD, five of 19 remained MCI, and five of 19 developed dementias other than AD. Both MCI cases of early Lewy body dementia (LBD) showed an AD-like metabolic pattern. CONCLUSIONS: Visual inspection proved reliable in determining normal from abnormal scans, but it proved unreliable at predicting diagnosis on follow-up. Computerized classification of MCI by using an AD-like metabolic template (such as derived from the averaged MCI images) showed potential to identify patients who will develop AD. However, the metabolic pattern in early LBD did not differ from that in AD.