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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. [ABSTRACT FROM AUTHOR]

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 Over the mean (SD) follow-up of 2.27 (1.22) years, participants receiving alpha tocopherol had slower decline than those receiving placebo as measured by the ADCS-ADL. The change translates into a delay in clinical progression of 19% per year compared with placebo (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). ADCS-ADL Inventory Baseline score, mean (SD) Least squares mean (SE) change from baseline Mean change difference compared with placebo (95% CI) Vitamin E (n = 140) 57.20 (14.38) -13.81 (1.11) 3.15 (0.92 to 5.39) Memantine (n = 142) 57.77 (13.78) -14.98 (1.10) 1.98 (-0.24 to 4.20) Vitamin E + Memantine (n = 139) 57.16 (13.59) -15.20 (1.11) 1.76 (-0.48 to 4.00) Placebo (n = 140) 56.93 (13.61) -16.96 (1.11) 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 [ABSTRACT FROM AUTHOR]

Focuses on a study that examined the cytokine production in patients with anorexia, bulimia and obesity. Clinical observations on the role of cytokines in eating disorders; Materials and methods used; Results; Conclusions.

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. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: At some point during their illness, drivers with dementia pose a public safety risk. Method: To address the issue of determining driving competence in drivers with dementia, the authors reviewed 11 studies. Results: When comparing different driving assessments, the authors found that while road tests, simulators, and neuropsychological tests are important, each has limitations. Conclusion: Neuropsychological tests that highlighted visual spatial skills, attention, and reaction time provided the most meaningful correlations with driving performance. Furthermore, the authors recommend that patients with MMSE scores of 24 or less have a driving evaluation, and that driving evaluations be repeated at six month intervals or more frequently if a noticeable decline is observed. Impact: Because many older adults with dementia continue to drive, competence must be addressed. [Copyright &y& Elsevier]

ObjectiveTo examine the safety and efficacy of sertraline augmentation therapy in the treatment of behavioral manifestations of Alzheimer's disease (AD) in outpatients treated with donepezil. Methods and materialsPatients with probable or possible AD, and a Neuropsychiatric Inventory (NPI) total score >5 (with a severity score ≥2 in at least one domain), were treated with donepezil (5–10 mg) for 8 weeks, then randomly assigned to 12 weeks of double-blind augmentation therapy with either sertraline (50–200 mg) or placebo. Primary efficacy measures were the 12-item Neuropsychiatric Inventory (NPI) and the Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales. Results24 patients were treated with donepezil+sertraline and 120 patients with donepezil+placebo. There were no statistically significant differences at endpoint on any of the three primary efficacy measures. However, a linear mixed model analysis found modest but statistically significantly greater improvements in the CGI-I score on donepezil+sertraline. Moreover, in a sub-group of patients with moderate-to-severe behavioral and psychological symptoms of dementia, 60% of patients on sertraline vs 40% on placebo (p = 0.006) achieved a response (defined as ≥;50% reduction in a four-item NPI-behavioral subscale). One adverse event (diarrhea) was significantly (p < 0.05) more common in the donepezil+sertraline group compared to the donepezil+placebo group. ConclusionSertraline augmentation was well-tolerated in this sample of AD outpatients. In addition, post hoc analyses demonstrated a modest but statistically significant advantage of sertraline over placebo augmentation in mixed model analyses and a clinically and statistically significant advantage in a subgroup of patients with moderate-to-severe behavioral and psychological symptoms of dementia. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Presents guidelines for prescribing psychoactive drugs. Prescribing recommendations; Information on antidepressants; Conclusion.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

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 D3 (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To estimate mortality risk associated with individual commonly prescribed antipsychotics. DESIGN: Five-year retrospective study. SETTING: Veterans national healthcare data. PARTICIPANTS: Predominantly male, aged 65 and older, with a diagnosis of dementia and no other indication for an antipsychotic. Subjects who received an antipsychotic were compared with randomly selected controls who did not. Exposed and control cohorts were matched according to their date of dementia diagnosis and time elapsed from diagnosis to the start of antipsychotic therapy. MEASUREMENTS: Mortality during incident antipsychotic use. RESULTS: Cohorts who were exposed to haloperidol (n=2,217), olanzapine (n=3,384), quetiapine (n=4,277), or risperidone (n=8,249) had more comorbidities than their control cohorts. During the first 30 days, there was a significant increase in mortality in subgroups prescribed a daily dose of haloperidol greater than 1 mg (hazard ratio (HR)=3.2, 95% confidence interval (CI)=2.2–4.5, P<.001), olanzapine greater than 2.5 mg (HR=1.5, 95% CI=1.1–2.0, P=.01), or risperidone greater than 1 mg (HR=1.6, 95% CI=1.1–2.2, P=.01) adjusted for demographic characteristics, comorbidities, and medication history using Cox regression analyses. Greater mortality was not seen when a daily dose of quetiapine greater than 50 mg (HR=1.2, 95% CI=0.7–1.8, P=.50) was prescribed, and there was no greater mortality associated with a dose less than 50 mg (HR=0.7, 95% CI=0.5–1.0, P=.03). No antipsychotic was associated with greater mortality after the first 30 days. CONCLUSION: Commonly prescribed doses of haloperidol, olanzapine, and risperidone, but not quetiapine, were associated with a short-term increase in mortality. Further investigations are warranted to identify patient characteristics and antipsychotic dosage regimens that are not associated with a greater risk of mortality in elderly patients with dementia. [ABSTRACT FROM AUTHOR]

Abstract: Even healthy adults worry about declines in mental efficiency with aging. Subjective changes in mental flexibility, self-regulation, processing speed, and memory are often cited. We show here that focal decreases in brain activity occur with normal aging as measured with fluorodeoxyglucose and positron emission tomography. The largest declines localize to a medial network including the anterior cingulate/medial prefrontal cortex, dorsomedial thalamus, and sugenual cingulate/basal forebrain. Declining metabolism in this network correlates with declining cognitive function. The medial prefrontal metabolic changes with aging are similar in magnitude to the hypometabolism found in Mild Cognitive Impairment or Alzheimer''s disease. These results converge with data from healthy elderly indicating dysfunction in the anterior attention system. The interaction of attention in the anterior cingulate cortex with memory in the medial temporal lobe may explain the global impairment that defines dementia. Despite the implications for an aging population, the neurophysiologic mechanisms of these metabolic decreases remain unknown. [Copyright &y& Elsevier]

Abstract: The clinical phenotype of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) varies. This variability is seen not only between kindreds with different mutations but also in families sharing the same mutation. Inheritance of tau haplotype (H1) and genotype (H1/H1) has been established as a risk factor for some neurodegenerative disorders with parkinsonism. We assessed the effect of tau polymorphism on the clinical features of FTDP-17 in 61 cases from 30 separately ascertained families with four different tau mutations, including P301L, +16, N279K, and P301S. There were no significant differences of age at symptomatic onset and disease duration between H1/H1 and H1/H2 genotypes. The comparison between tau genotype and type of initial clinical sign showed an association between the H1/H1 genotype and parkinsonian phenotype and between the H1/H2 genotype and frontotemporal dementia phenotype (OR=11.7; 95% confidence interval, 1.4–98.7; P=0.008). Our results suggest that tau genotype does not influence the disease course. However, it may predispose to a specific clinical sign in the early stage of FTDP-17. [Copyright &y& Elsevier]

Rebecca C. Rossom et al. respond to a letter to the editor submitted in response to their article "Calcium and Vitamin D Supplementation and Cognitive Impairment in the Women’s Health Initiative".

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). [ABSTRACT FROM AUTHOR]