The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain-only donations and currently has banked more than 1600 brains. More than 430 whole-body donations have been received since this service was commenced in 2005. The collective academic output of the BBDP is now described as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are enrolled as cognitively normal volunteers residing in the retirement communities of metropolitan Phoenix, Arizona. Specific recruitment efforts are also directed at subjects with Alzheimer’s disease, Parkinson’s disease and cancer. The median age at death is 82. Subjects receive standardized general medical, neurological, neuropsychological and movement disorders assessments during life and more than 90% receive full pathological examinations by medically licensed pathologists after death. The Program has been funded through a combination of internal, federal and state of Arizona grants as well as user fees and pharmaceutical industry collaborations. Subsets of the Program are utilized by the US National Institute on Aging Arizona Alzheimer’s Disease Core Center and the US National Institute of Neurological Disorders and Stroke National Brain and Tissue Resource for Parkinson’s Disease and Related Disorders. Substantial funding has also been received from the Michael J. Fox Foundation for Parkinson’s Research. The Program has made rapid autopsy a priority, with a 3.0-hour median postmortem interval for the entire collection. The median RNA Integrity Number (RIN) for frozen brain and body tissue is 8.9 and 7.4, respectively. More than 2500 tissue requests have been served and currently about 200 are served annually. These requests have been made by more than 400 investigators located in 32 US states and 15 countries. Tissue from the BBDP has contributed to more than 350 publications and more than 200 grant-funded projects.

A Randomized Clinical Trial of High-Dosage Coenzyme Q10 in Early Parkinson Disease No Evidence of Benefit The Parkinson Study Group QE3 Investigators IMPORTANCE Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. OBJECTIVE To examine whether CoQ10 could slow disease progression in early PD. DESIGN, SETTING, AND PARTICIPANTS A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. INTERVENTIONS The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E. MAIN OUTCOMES AND MEASURES Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. RESULTS The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo). CONCLUSIONS AND RELEVANCE Coenzyme Q10 was safe and well tolerated in this population, bu...

IntroductionLongitudinal assessment of cognitive decline in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) often involves the use of both informant-based and objective cognitive assessments. As efforts have focused on identifying individuals in pre-clinical stages, instruments that are sensitive to subtle cognitive changes are needed. The Alzheimer’s Questionnaire (AQ) has demonstrated high sensitivity and specificity in identifying aMCI and AD; however its ability to measure longitudinal change has not been assessed. The aims of this study are to assess the sensitivity to change of the AQ and to determine whether the AQ predicts change in global cognition and function in cognitively normal (CN), aMCI, and AD subjects.MethodsData from 202 individuals participating in a brain and body donation program were utilized for this study (101 CN, 62 aMCI, 39 AD). AD and aMCI individuals were matched on age, education, and gender to CN individuals. Sensitivity to change of the AQ was assessed in addition to the AQ’s ability to predict change in global cognition and function. The Mini Mental State Exam (MMSE) and Functional Activities Questionnaire (FAQ) were used as gold standard comparisons of cognition and function. Sample size calculations for a 25% treatment effect were also carried out for all three groups.ResultsThe AQ demonstrated small sensitivity to change in the aMCI and CN groups (d = 0.33, d = 0.23, respectively) and moderate sensitivity to change in the AD group (d = 0.43). The AQ was associated with increases in the Clinical Dementia Rating Global Score (OR = 1.20 (1.09, 1.32), P <0.001). Sample size calculations found that the AQ would require substantially fewer subjects than the MMSE given a 25% treatment effect.ConclusionsAlthough the AQ demonstrated small sensitivity to change in aMCI and CN individuals in terms of effect size, the AQ may be superior to objective cognitive tests in terms of required sample size for a clinical trial. As clinicians and researchers continue to identify and treat individuals in earlier stages of AD, there is a need for instruments that are sensitive to cognitive changes in these earlier stages.

Abstract Multiple studies suggest that females are affected by Alzheimer disease (AD) more severely and more frequently than males. Other studies have failed to confirm this and the issue remains controversial. Difficulties include differences in study methods and male versus female life expectancy. Another element of uncertainty is that the majority of studies have lacked neuropathological confirmation of the AD diagnosis. We compared clinical and pathological AD severity in 1028 deceased subjects with full neuropathological examinations. The age of dementia onset did not differ by gender but females were more likely to proceed to very severe clinical and pathological disease, with significantly higher proportions having a Mini-Mental State Examination score of 5 or less and Braak stage VI neurofibrillary degeneration. Median neuritic plaque densities were similar in females and males with AD but females had significantly greater tangle density scores. In addition, we found that AD-control brain weight differences were significantly greater for females, even after adjustment for age, disease duration, and comorbid conditions. These findings suggest that when they are affected by AD, females progress more often to severe cognitive dysfunction, due to more severe neurofibrillary degeneration, and greater loss of brain parenchyma.