Aakre, Jeremiah A.

AbstractObjectiveTo examine the association of baseline elevated brain amyloid and neurodegeneration with changes in activities of daily living in participants without dementia (ND; i.e., cognitively unimpaired and participants with mild cognitive impairment) at baseline in the population‐based Mayo Clinic Study of Aging.MethodsWe included 1747 ND participants with 11C‐PiB PET and MR imaging in the study, with data on activities of daily living (as assessed by the Functional Activities Questionnaire (FAQ) and the Clinical Dementia Rating scale Sum of Boxes for functional domains (CDR‐SOB (functional)), with a median (range) of 4.3 (0.0–12.7) years of follow‐up. Abnormal (elevated; A+) 11C‐PiB‐PET retention ratio was defined as standardized uptake value ratio ≥ 1.48, and abnormal (reduced) AD signature cortical thickness as ≤ 2.68 mm (neurodegeneration; N+). Associations were examined with mixed effects models, adjusting for age, sex, education, apolipoprotein E ε4 allele carrier status, and global cognitive z‐score.ResultsMean age (SD) was 71.4 years (10.1), 46.7% were females, 195 (11.2%) had A+N‐, 442 (25.3%) had A‐N+, and 339 (19.4%) had A+N+ biomarkers. The A+N+ group had the largest annualized change in the FAQ score from baseline (difference in annual change A+N+ vs. A‐N‐; ß (SE): 0.80 (0.07)); associations were substantially attenuated when a time‐varying global cognitive composite was included in the model (A+N+ vs. A‐N‐; ß (SE): 0.31 (0.05)). CDR‐SOB (functional) findings partly agreed with FAQ score findings.InterpretationThe longitudinal increase in functional limitations is greater for individuals with abnormal neuroimaging biomarkers, especially for those with both elevated brain amyloid and neurodegeneration.

AbstractIntroductionPractical algorithms predicting the probability of amyloid pathology among patients with subjective cognitive decline or mild cognitive impairment may help clinical decisions regarding confirmatory biomarker testing for Alzheimer's disease.MethodsAlgorithm feature selection was conducted with Alzheimer's Disease Neuroimaging Initiative and Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing data. Probability algorithms were developed in Alzheimer's Disease Neuroimaging Initiative using nested cross‐validation accompanied by stratified subsampling to obtain 1000 internally validated decision trees. Semi‐independent validation was conducted using Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing. Independent external validation was conducted in the population‐based Mayo Clinic Study of Aging.ResultsTwo algorithms were developed using age and normalized immediate recall z‐scores, with or without apolipoprotein E ε4 carrier status. Both algorithms had robust performance across data sets and when substituting different recall memory tests.DiscussionThe statistical framework resulted in robust probability estimation. Application of these algorithms may assist in clinical decision‐making for further testing to diagnose amyloid pathology.

AbstractBackground: hearing loss has been associated with mild cognitive impairment (MCI) and dementia. Studies have not assessed whether hearing difficulties (HD) that interfere with daily activities as reported by partners can be a marker for increased risk for cognitive decline and impairment.Objective: to assess the cross-sectional and longitudinal associations between informant-based HD, which interfere with daily activities and the risk for MCI and dementia.Methods: the study included 4812 participants without dementia, enrolled in the Mayo Clinic Study of Aging (mean age (SD) 73.7 (9.6) years) with cognitive evaluation and informant-based report on participant’s HD that interfere significantly with daily activities at baseline and for every 15 months. Cox proportional hazards models (utilising time-dependent HD status and age as the time scale) were used to examine HD and the risk for MCI or dementia, and mixed-effects models (allowing for random subject-specific intercepts and slopes) were used to examine the relationship between HD and cognitive decline.Results: about, 981 participants had HD and 612 (12.7%) had prevalent MCI at baseline; 759 participants developed incident MCI and 273 developed incident dementia. In cognitively unimpaired participants at baseline, those with HD had higher risk for MCI (hazard ratio [HR] = 1.29, 95% confidence interval [CI] (1.10, 1.51), P = 0.002; adjusting for sex, years of education). In participants without dementia, those with HD had higher risk for dementia (HR: 1.39, 95% CI, (1.08–1.79), P = 0.011; adjusting sex and education). In individuals with MCI, HD was associated with modestly greater cognitive decline.Conclusions: informant-based HD was associated with increased risk for MCI and dementia.

There has been no comparison of excessive daytime sleepiness (EDS) in patients with Alzheimer’s disease dementia (AD), dementia with Lewy bodies (DLB), and behavioral variant frontotemporal dementia (bvFTD). We identified patients with mild dementia who met criteria for these disorders who also had the Epworth Sleepiness Scale (ESS) completed. The sample included 17 bvFTD, 111 AD, and 31 DLB. An ESS score ≥10 was considered abnormal and consistent with EDS. Analyses with age and sex as covariates revealed higher mean ESS scores for DLB compared to the other groups (DLB 13.9 [5], bvFTD 9.6 [8], AD 8.8 [5], P < .05). An ESS score ≥10 was significantly more likely to occur in DLB compared to bvFTD or AD (DLB 81% vs bvFTD 47% vs AD 45%, P < .01). In patients with mild dementia, EDS is greatest in DLB and comparably lower in bvFTD and AD.

Objective: To determine the frequency and characteristics of symptomatic intracerebral hemorrhage in a population-based study Patients and Methods: The population-based Mayo Clinic Study of Aging included 4,994 participants age ≥50 years entered from 11/29/2004 to 3/11/2017. Participants with intracranial hemorrhage were identified using the Rochester Epidemiology Project medical records linkage system. Medical records of these individuals were reviewed. Each hemorrhage was classified as deep, lobar, or cerebellar intracerebral hemorrhage (ICH) or convexity subarachnoid hemorrhage (cSAH). Traumatic, subdural, non-convexal SAH, and epidural hemorrhages were excluded. Patient demographics, presence of hypertension, antithrombotic regimen, APOE genotype, and amyloid PET scan results were collected when available. Individuals with hemorrhages were matched 3:1 on age and gender to controls without symptomatic hemorrhage. Analyses within the cases and between the groups were performed. Results: Symptomatic hemorrhages were identified in 57 individuals for a frequency of 1.14%. Twenty-one were classified as deep, 26 lobar, 5 cerebellar, and 5 cSAH. Mean age at the time of hemorrhage was 80.9 years (SD ±7.9). 54.4% of hemorrhages occurred in men. Hypertension was present in 45.6%. Of those with lobar ICH or cSAH, 87.1% were on an antithrombotic compared to 65.6% of controls (p=0.02) and 32.3% of these were on warfarin compared to 12.9% of controls (p=0.01). APOE genotype was available in 54 of the 57. APOE e2 and/or e4 was found in 46.7% of those with lobar ICH/cSAH compared to 39.1% of controls (p=0.47) and 35.0% of those with deep ICH versus 39.3% of controls (p=0.73). Of the 31 with either lobar ICH or cSAH, 7 underwent amyloid PET scans; of these, 71.4% were abnormal compared to 42.9% of controls with mean SUVR of 1.911 and 1.565, respectively (p=0.08). Conclusions: Symptomatic ICH occurred in approximately 1 in 100 individuals age 50-94 years in this population-based study. In a matched case-control study, antithrombotic use (particularly warfarin) was statistically associated with the development of an ICH. While only a subset underwent amyloid PET, there was a trend towards greater amyloid load in those who developed a lobar or cSAH compared to controls.

Objectives To examine the cross‐sectional association between functional performance and Alzheimer's disease (AD) neuroimaging biomarkers in individuals without dementia (cognitively unimpaired (CU), and those with mild cognitive impairment (MCI)). Design Cross‐sectional. Setting Olmsted County, Minnesota. Participants Population‐based Mayo Clinic Study of Aging (MCSA) participants (aged ≥ 50, mean age 71.3 ± 10.2; 53.4% male; 28.3% apolipoprotein (APO)E ε4 allele carriers, 1,578 CU, 204 MCI) who underwent 11 C‐Pittsburgh compound B ( 11 C‐PiB) positron emission tomography (PET) (N=1,782). Measurements We defined an abnormal (high) 11 C‐PiB‐PET retention ratio as a standardized uptake value ratio greater than 1.42 (high amyloid; A+), abnormal (reduced) AD signature cortical thickness (neurodegeneration; N+) as less than 2.67 mm (MRI measurement), and biomarker groups according to the combination of abnormality (or not) for amyloid accumulation (A+/A–) and neurodegeneration (N+/N–). Functional performance was assessed using the Clinical Dementia Rating (CDR) Sum of Boxes (SOB) for functional domains and the Functional Activities Questionnaire (FAQ). Results Participants with a CDR‐SOB (functional) score greater than 0 were almost 4 times as likely to have N + (odds ratio (OR)=3.92, 95% confidence interval (CI)=1.77–8.67, adjusting for age, sex, education, global cognitive z‐score, and APOE ε4 allele status; p<.001) and those with a FAQ score greater than 0 were 1.5 times as likely to have A + (OR=1.48, 95% CI=1.04–2.11, p=.03). Higher FAQ scores were associated with greater odds of A+N + and A–N + in CU participants. Conclusion The findings of this cross‐sectional study supplement limited available information that supports an association between functional performance and AD neuroimaging biomarkers very early in the dementia pathophysiology. The associations should be validated in longitudinal studies. J Am Geriatr Soc 66:2274–2281, 2018 .

Background: Non-traumatic convexal subarachnoid hemorrhages (cSAH) in the elderly can be a manifestation of cerebral amyloid angiopathy (CAA) and predict future intracerebral hemorrhage risk. The frequency of cSAH in the elderly population is unknown. Our objective was to determine the frequency of convexal subarachnoid hemorrhage in a population-based study among individuals who underwent amyloid PET imaging. Methods: Between 11/29/2004 and 3/11/2017 there were 1,687 participants ages 50-years and older in the population-based Mayo Clinic Study of Aging (MCSA) with Pittsburgh compound B (PiB) PET imaging. All intracerebral hemorrhages among participants were identified utilizing the Rochester Epidemiology Project’s records linkage system, and records and images were reviewed to identify those with both symptomatic and asymptomatic convexal subarachnoid hemorrhage. Neuroimaging characteristics, demographics, medications, and ApoE genotype were recorded. Results: Four (0.23%) cSAHs were identified among the individuals who underwent PiB PET imaging. Three were women and median age was 73 (range: 67-84). cSAH occurred in the following locations: right frontal (3), and right parieto-occipital (1). Two went on to develop a lobar intracerebral hemorrhage at a median of 4.75 years after cSAH. Coexisting cerebral microbleeds were identified in one case. The APOE allele combinations of the four participants were: 3/3, 3/3, 2/2, and 2/3. On PiB PET imaging, the median SUVR was 1.81 (range: 1.38-2.34). Conclusion: cSAH is a relatively rare manifestation of CAA occurring in less than 1% of the general population, but may represent a subset with a high risk of future intracerebral hemorrhage. Half of the participants with cSAH had an APOE e2 allele.

2067 Background: An estimated 2% of the general population has a meningioma (Vernooij et al. 2007), which accounts for about 36% of all primary intracranial tumors (Ostrom et al. 2015). The most established risk factors are older age and female gender. One small study identified gender but no other risk factors with meningioma (Krampla et al 2004). A larger study using the Iowa Women’s Health study data found lower levels of physical activity, greater body mass index (BMI), greater height and uterine fibroids were associated with meningioma (Johnson et al. 2011). We sought to replicate these findings and to identify additional risk factors related to meningioma in a large population-based sample. Methods: Study participants were enrolled in the Mayo Clinic Study of Aging (MCSA), a population-based sample of Olmsted County, Minnesota residents used to study prevalence, incidence, and risk-factors for Mild Cognitive Impairment and dementia and includes a variety of medical factors. Using a text search of radiologists’ notes of 2,402 MCSA individuals, mean age 77±8 years and scanned between 2004-2014.We identified 52 subjects who had at least one meningioma. We estimated the association of selected potential risk factors with presence of meningioma using odds ratios and 95% confidence intervals from logistic regression models adjusted for age and gender, which informed the multivariable models. Results: In the initial models, significant risk factors identified included BMI (as a continuous variable) (OR = 1.06 95%CI 1.01 to 1.12), taking NSAIDS (OR = 2.11, 95%CI 1.13 to 3.95), aspirin (OR = 1.90, 95%CI 1.04 to 3.46), and blood pressure lowering medication (OR = 2.06, 95%CI 1.07 to 3.99). Protective factors included male gender (OR = 0.51, 95%CI 0.29 to 0.90), coronary artery disease (CAD; OR = 0.46, 95%CI 0.22 to 0.97) and higher Beck Anxiety Inventory (BAI) total score (OR = 0.88, 95%CI 0.78 to 0.98). Simultaneous adjustment for these factors in a multivariable model did not attenuate these associations. Conclusions: Findings reveal gender and BMI as risk factors for meningioma. Additionally, certain medications such as NSAIDS and BP lowering medications warrant follow up as potential factors related to development of meningioma.