Wiste, Heather J.

Objective The newly proposed National Institute on Aging–Alzheimer's Association (NIA‐AA) criteria for mild cognitive impairment (MCI) due to Alzheimer disease (AD) suggest a combination of clinical features and biomarker measures, but their performance in the community is not known. Methods The Mayo Clinic Study of Aging (MCSA) is a population‐based longitudinal study of nondemented subjects in Olmsted County, Minnesota. A sample of 154 MCI subjects from the MCSA was compared to a sample of 58 amnestic MCI subjects from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI‐1) to assess the applicability of the criteria in both settings and to assess their outcomes. Results Fourteen percent of MCSA and 16% of ADNI‐1 of subjects were biomarker negative. In addition, 14% of MCSA and 12% of ADNI‐1 subjects had evidence for amyloid deposition only, whereas 43% of MCSA and 55% of ADNI‐1 subjects had evidence for amyloid deposition plus neurodegeneration (magnetic resonance imaging atrophy, fluorodeoxyglucose positron emission tomography hypometabolism, or both). However, a considerable number of subjects had biomarkers inconsistent with the proposed AD model; for example, 29% of MCSA subjects and 17% of ADNI‐1 subjects had evidence for neurodegeneration without amyloid deposition. These subjects may not be on an AD pathway. Neurodegeneration appears to be a key factor in predicting progression relative to amyloid deposition alone. Interpretation The NIA‐AA criteria apply to most MCI subjects in both the community and clinical trials settings; however, a sizeable proportion of subjects had conflicting biomarkers, which may be very important and need to be explored. Ann Neurol 2013;74:199–208

The authors aimed to compare renal function by estimated glomerular filtration rate and albuminuria in 3 groups of women: nulliparous women, women with a history of normotensive pregnancies, and women with a history of at least one hypertensive pregnancy. Women who participated in the second F amily B lood P ressure P rogram S tudy visit (2000–2004) and had serum creatinine and urine albumin measurements (n=3015) were categorized as having had no pregnancy lasting >6 months (n=341), having had only normotensive pregnancies (n=2199), or having had at least 1 pregnancy with hypertension (n=475) based on a standardized questionnaire. Women who reported having had at least one pregnancy with hypertension were significantly more likely to be hypertensive (75.6% vs 59.4%, P <.001), diabetic (34.2% vs 27.3%, P ≤.001), and have higher body mass index (32.8 vs 30.5, P <.001) than those who reported normotensive pregnancies. There was a significantly greater risk of microalbuminuria (urine albumin‐creatinine ratio >25 mg/g) in those who reported at least one pregnancy with hypertension ( odds ratio, 1.37; confidence interval, 1.02–1.85; P =.04) than in those with normotensive pregnancies, after adjusting for risk factors for chronic kidney and cardiovascular disease. Hypertension in pregnancy is associated with an increased risk of future microalbuminuria.

BackgroundOctogenarians (>80 years) have been underrepresented in clinical trials of cardiac resynchronization therapy (CRT).ObjectiveTo determine the benefit of CRT with or without a defibrillator in older elderly patients.MethodsWe retrospectively studied consecutive patients who received CRT at our institution from 2002 through 2008. New York Heart Association (NYHA) class and echocardiographic parameters were assessed before and after CRT. Thirty‐day complications after device implant were collected. Survival data were obtained from the national death and location database. Data were compared between those 80 years and younger and those older than 80 years.ResultsOf 728 patients identified, 90 (12.4%) were older than 80 years. After CRT, older and younger patients had similar improvements in NHYA class (P = 0.41), ejection fraction (P = 0.48), and mitral valve regurgitation (MR) severity (P = 0.42). In the older patients, defibrillator implantation was associated with comparable improvement in NYHA class, ejection fraction, and MR grade severity (P > 0.05), as in those without a defibrillator. Overall survival was worse in octogenarians than in the younger patients by Kaplan‐Meier estimates (P = 0.001). Multivariate analysis showed similar survival between the younger and older subjects (hazard ratio, 1.23; 95% confidence interval, 0.83–1.84; P = 0.31). The observed complication rate in all study subjects was 12.2%, with no difference between the two age groups.ConclusionOctogenarian patients who received CRT with or without a defibrillator for advanced heart failure had similar clinical benefits as younger patients. CRT should not be withheld from octogenarians meeting current selection guidelines.

ObjectiveThe new criteria for preclinical Alzheimer disease (AD) proposed 3 stages: abnormal levels of β‐amyloid (stage 1), stage 1 plus evidence of brain injury (stage 2), and stage 2 plus subtle cognitive changes (stage 3). However, a large group of subjects with normal β‐amyloid biomarkers have evidence of brain injury; we labeled them as the “suspected non‐Alzheimer pathophysiology” (sNAP) group. The characteristics of the sNAP group are poorly understood.MethodsUsing the preclinical AD classification, 430 cognitively normal subjects from the Mayo Clinic Study of Aging who underwent brain magnetic resonance (MR), 18fluorodeoxyglucose (FDG), and Pittsburgh compound B positron emission tomography (PET) were evaluated for FDG PET regional volumetrics, MR regional brain volumetrics, white matter hyperintensity volume, and number of infarcts. We examined cross‐sectional associations across AD preclinical stages, those with all biomarkers normal, and the sNAP group.ResultsThe sNAP group had a lower proportion (14%) with apolipoprotein E ε4 genotype than the preclinical AD stages 2 + 3. The sNAP group did not show any group differences compared to stages 2 + 3 of the preclinical AD group on measures of FDG PET regional hypometabolism, MR regional brain volume loss, cerebrovascular imaging lesions, vascular risk factors, imaging changes associated with α‐synucleinopathy, or physical findings of parkinsonism.InterpretationCognitively normal persons with brain injury biomarker abnormalities, with or without abnormal levels of β‐amyloid, were indistinguishable on a variety of imaging markers, clinical features, and risk factors. The initial appearance of brain injury biomarkers that occurs in cognitively normal persons with preclinical AD may not depend on β‐amyloidosis. ANN NEUROL 2013;73:472–480