Heather S. Anderson

Cardiorespiratory fitness and brain atrophy in early Alzheimer disease

Objective: To examine the correlation of cardiorespiratory fitness with brain atrophy and cognition in early-stage Alzheimer disease (AD). Background: In normal aging physical fitness appears to mitigate functional and structural age-related brain changes. Whether this is observed in AD is not known. Methods: Subjects without dementia (n = 64) and subjects with early-stage AD (n = 57) had MRI and standard clinical and psychometric evaluations. Peak oxygen consumption (VO2peak), the standard measure of cardiorespiratory fitness, was assessed during a graded treadmill test. Normalized whole brain volume, a brain atrophy estimate, was determined by MRI. Pearson correlation and linear regression were used to assess fitness in relation to brain volume and cognitive performance. Results: Cardiorespiratory fitness (VO2peak) was modestly reduced in subjects with AD (34.7 [5.0] mL/kg/min) vs subjects without dementia (38.1 [6.3] mL/kg/min, p = 0.002). In early AD, VO2peak was associated with whole brain volume (beta = 0.35, p = 0.02) and white matter volume (beta = 0.35, p = 0.04) after controlling for age. Controlling for additional covariates of sex, dementia severity, physical activity, and physical frailty did not attenuate the relationships. VO2peak was associated with performance on delayed memory and digit symbol in early AD but not after controlling for age. In participants with no dementia, there was no relationship between fitness and brain atrophy. Fitness in participants with no dementia was associated with better global cognitive performance (r = 0.30, p = 0.02) and performance on Trailmaking A and B, Stroop, and delayed logical memory but not after controlling for age. Conclusions: Increased cardiorespiratory fitness is associated with reduced brain atrophy in Alzheimer disease (AD). Cardiorespiratory fitness may moderate AD-related brain atrophy or a common underlying AD-related process may impact both brain atrophy and cardiorespiratory fitness. GLOSSARY: AD = Alzheimer disease; CDR = Clinical Dementia Rating; MMSE = Mini-Mental State Examination; PASE = Physical Activity Scale in the Elderly.

Cardiorespiratory Fitness and Preserved Medial Temporal Lobe Volume in Alzheimer Disease

Exercise and cardiorespiratory (CR) fitness may moderate age-related regional brain changes in nondemented (ND) older adults. The relationship of fitness to Alzheimer disease (AD)-related brain change is understudied, particularly in the hippocampus, which is disproportionately affected in early AD. The role of apolipoprotein E4 (apoE4) genotype in modulating this relationship is also unknown. ND (n=56) and early-stage AD patients (n=61) over the age of 65 years had magnetic resonance imaging and CR fitness assessments. Voxel-based morphometry techniques were used to identify AD-related atrophy. We analyzed the relationship of CR fitness with white and gray matter within groups, assessed fitness-related brain volume change in areas most affected by AD-related atrophy, and then analyzed differential fitness-brain relationships between apoE4 carriers. Atrophy was present in the medial temporal, temporal, and parietal cortices in patients with mild AD. There was a significant positive correlation of CR fitness with parietal and medial temporal volume in AD patients. ND patients did not have a significant relationship between brain volume and CR fitness in the global or small volume correction analyses. There was not a significant interaction for fitness×apoE4 genotype in either group. In early-stage AD, CR fitness is associated with regional brain volumes in the medial-temporal and parietal cortices suggesting that maintaining CR fitness may modify AD-related brain atrophy.

Peripheral insulin and brain structure in early Alzheimer disease

Objective: Accumulating evidence suggests insulin and insulin signaling may be involved in the pathophysiology of Alzheimer disease (AD). The relationship between insulin-mediated glucoregulation and brain structure has not been assessed in individuals with AD. Methods: Nondemented (Clinical Dementia Rating [CDR] 0, n = 31) and early stage AD (CDR 0.5 and 1, n = 31) participants aged 65 years and older had brain MRI to determine whole brain and hippocampal volume and 3-hour IV glucose tolerance tests to determine glucose and insulin area under the curve (AUC). Linear regression models were used to assess the relationship of insulin and glucose with brain volume, cognition, and dementia severity. Results: In early AD, insulin and glucose AUCs were related to whole brain (insulin β = 0.66, p < 0.001; glucose β = 0.45, p < 0.01) and hippocampal volume (insulin β = 0.42, p < 0.05; glucose β = 0.46, p < 0.05). These relationships were independent of age, sex, body mass index, body fat, cardiorespiratory fitness, physical activity, cholesterol, and triglycerides. Insulin AUC, but not glucose, was associated with cognitive performance in early AD (β = 0.40, p = 0.04). Insulin AUC was associated with dementia severity (Pearson r = −0.40, p = 0.03). Glucose and insulin were not related to brain volume or cognitive performance in nondemented individuals. Conclusions: Increased peripheral insulin is associated with reduced Alzheimer disease (AD)–related brain atrophy, cognitive dysfunction, and dementia severity, suggesting that insulin signaling may play a role in the pathophysiology of AD.

Cardiorespiratory fitness in early-stage Alzheimer disease.

There is an increasing interest in exercise and fitness in Alzheimer disease (AD) given evidence suggesting a role in the maintenance of cognitive health. There is, however, little data on the objective measure of cardiorespiratory fitness in individuals with AD. Thus, we assessed cardiorespiratory fitness in early AD and its relationship with physical activity levels, health markers, and cognitive performance in nondemented (Clinical Dementia Rating 0, n=31) and early-stage AD (Clinical Dementia Rating 0.5 and 1, n=31) participants. Cardiorespiratory fitness was assessed with maximal exercise testing to determine peak oxygen consumption (VO2peak). Additionally, dual emission x-ray absorptiometry scanning for body composition and glucose tolerance tests were conducted. Despite reductions in physical performance and habitual physical activity levels in early AD, cardiorespiratory fitness (VO2peak) was comparable in the 2 groups (19.8 in early AD vs. 21.2 mL/kg/min in nondemented, P=0.26). AD participants performed well on treadmill tests with similar levels of perceived exertion, maximal heart rate, and respiratory exchange ratio compared with nondemented individuals. After controlling for age and sex, VO2peak was associated with a beneficial glucoregulatory profile and inversely associated with percent body fat, body mass index, and triglycerides. A relationship between cognitive performance measures and VO2peak was not apparent. These results suggest that individuals in the early stages of AD have the capacity for maximal exercise testing and have comparable levels of cardiorespiratory fitness as nondemented individuals. Reduced physical activity associated with early AD underscores the need for further defining the role of exercise as a potential therapeutic intervention in the early stages of AD.

A community-based approach to trials of aerobic exercise in aging and Alzheimer's disease.

The benefits of exercise for aging have received considerable attention in both the popular and academic press. The putative benefits of exercise for maximizing cognitive function and supporting brain health have great potential for combating Alzheimers disease (AD). Aerobic exercise offers a low-cost, low-risk intervention that is widely available and may have disease modifying effects. Demonstrating that aerobic exercise alters the AD process would have enormous public health implications. The purpose of this paper is to report the protocol of a current, community-based pilot study of aerobic exercise for AD to guide future investigation. This manuscript provides 1) an overview of possible benefits of exercise in those with dementia, 2) a rationale and recommendations for implementation of a community-based approach, 3) recommendation for implementation of similar study protocols, and 4) unique challenges in conducting an exercise trial in AD.

Reliability of Peak Treadmill Exercise Tests in Mild Alzheimer Disease

ABSTRACT Introduction: The purpose of this study was to determine the reliability of treadmill peak exercise testing in people with very mild-to-mild Alzheimer disease (AD). Methods: Sixteen subjects with very mild-to-mild AD performed graded peak treadmill exercise tests twice within a 14-day period. Heart rate, oxygen consumption, and respiratory exchange ratio (RER) were continuously monitored. Peak values were analyzed for absolute level of agreement. Results: Fourteen participants (87.5%) completed testing. Reliability was excellent with total peak oxygen consumption (VO2peak) (ml/kg/min) highly correlated across the two tests (r = 0.94, p < .001) with an intraclass correlation coefficient (ICC[3,1]) of 0.92 (95% confidence interval (CI) = 0.78, 0.97). The standard error of measurement (SEM) for VO2peak was 1.29 (95% CI = 0.88, 1.89). Conclusions: These results indicate that peak exercise testing on a treadmill is reliable in the early stages of AD.

Status of neurology medical school education Results of 2005 and 2012 clerkship director survey

Objective: To survey all US medical school clerkship directors (CDs) in neurology and to compare results from a similar survey in 2005. Methods: A survey was developed by a work group of the American Academy of Neurology Undergraduate Education Subcommittee, and sent to all neurology CDs listed in the American Academy of Neurology database. Comparisons were made to a similar 2005 survey. Results: Survey response rate was 73%. Neurology was required in 93% of responding schools. Duration of clerkships was 4 weeks in 74% and 3 weeks in 11%. Clerkships were taken in the third year in 56%, third or fourth year in 19%, and fourth year in 12%. Clerkship duration in 2012 was slightly shorter than in 2005 (fewer clerkships of ≥4 weeks, p = 0.125), but more clerkships have moved into the third year (fewer neurology clerkships during the fourth year, p = 0.051). Simulation training in lumbar punctures was available at 44% of schools, but only 2% of students attempted lumbar punctures on patients. CDs averaged 20% protected time, but reported that they needed at least 32%. Secretarial full-time equivalent was 0.50 or less in 71% of clerkships. Eighty-five percent of CDs were “very satisfied” or “somewhat satisfied,” but more than half experienced “burnout” and 35% had considered relinquishing their role. Conclusion: Trends in neurology undergraduate education since 2005 include shorter clerkships, migration into the third year, and increasing use of technology. CDs are generally satisfied, but report stressors, including inadequate protected time and departmental support.

AEROBIC EXERCISE REDUCES HIPPOCAMPAL ATROPHY IN INDIVIDUALS WITH EARLY ALZHEIMER'S DISEASE

Owen Thomas Carmichael, Tom Meade, Dementia Research Centre, London, England, United Kingdom; London School of Hygiene and Tropical Medicine, London, United Kingdom; UCL, London, United Kingdom; London School of Hygiene and Tropical Medicine, London; University College London, London, United Kingdom; UCL Institute of Neurology, London, United Kingdom; University of California, Davis, Davis, California, United States. Contact e-mail: jennifer.nicholas@lshtm. ac.uk

Independent or Integrated? The Impact on Subject Examination Scores of Changing a Neuropsychiatry Clerkship to Independent Clerkships in Psychiatry and Neurology

ObjectiveThis study was undertaken to assess any impact on National Board of Medical Examiners (NBME) neurology and psychiatry subject examination scores of changing from an integrated neuropsychiatry clerkship to independent neurology and psychiatry clerkships.MethodsNBME psychiatry and neurology subject examinations scores were compared for all 625 students completing the required neuropsychiatry clerkship in academic years 2005–2006 through 2008–2009 with all 650 students completing the independent neurology and psychiatry clerkships in academic years 2009–2010 through 2012–2013. Statistical adjustments were made to ensure comparability across groups and over time.ResultsA significant improvement in subject examination scores was associated with the independent clerkships.ConclusionsThe independent clerkship model was associated with a modest improvement in NBME subject examination scores. This finding may be attributable to many causes or combination of causes other than curricular design. Curricular planners need to pay attention to the potential impact of course integration on specialty-specific NBME subject examination performance.

Dementia, Delirium, and Depression

Concern about an older adult’s cognitive function is common, so any clinician involved in the care of older adults needs to be familiar with conditions which can affect cognitive function. Dementia, delirium, and depression can all cause memory loss and confusion, and all three conditions have different presentations and treatments. This chapter reviews the etiology, clinical evaluation and treatment options for dementia, delirium and depression in geriatric patients, and the relationship of these conditions to urologic healthcare for older adults.