Untreated Type 2 Diabetes and Its Complications Are Associated With Subcortical Infarctions

OBJECTIVE - To investigate the association of type 2 diabetes with subcortical infarctions. RESEARCH DESIGN AND METHODS - We investigated this association in subjects with type 2 diabetes (case subjects; n = 93) and without type 2 diabetes (control subjects; n = 186), matched by age, sex, and years of education. Participants were a subset of the Mayo Clinic Study of Aging (median age 79 years) who had undergone magnetic resonance imaging. RESULTS - The frequency of subcortical infarctions was 39% in case subjects and 29% in control subjects (odds ratio 1.59 [95% CI 0.91-2.75]). The association was stronger in case subjects without treatment (2.60 [1.11- 6.08]) and in case subjects with diabetes-related complications (1.96 [1.02-3.74]) compared with control subjects. CONCLUSIONS - These findings suggest that untreated type 2 diabetes and type 2 diabetes with complications are associated with subcortical infarctions. © 2011 by the American Diabetes Association

Frequency and topography of cerebral microbleeds in dementia with Lewy bodies compared to Alzheimer's disease

AbstractAimTo determine the frequency and topographic distribution of cerebral microbleeds (CMBs) in dementia with Lewy bodies (DLB) in comparison to CMBs in Alzheimer disease dementia (AD).MethodsConsecutive probable DLB (n = 23) patients who underwent 3-T T2* weighted gradient-recalled-echo MRI, and age and gender matched probable Alzheimer's disease patients (n = 46) were compared for the frequency and location of CMBs.ResultsThe frequency of one or more CMBs was similar among patients with DLB (30%) and AD (24%). Highest densities of CMBs were found in the occipital lobes of patients with both DLB and AD. Patients with AD had greater densities of CMBs in the parietal, temporal lobes and infratentorial regions compared to DLB (p < 0.05).ConclusionCMBs are as common in patients with DLB as in patients with AD, with highest densities observed in the occipital lobes, suggesting common pathophysiologic mechanisms underlying CMBs in both diseases

Quality of care assessment in geriatric evaluation and management units: construction of a chart review tool for a tracer condition

<p>Abstract</p> <p>Background</p> <p>The number of elderly people requiring hospital care is growing, so, quality and assessment of care for elders are emerging and complex areas of research. Very few validated and reliable instruments exist for the assessment of quality of acute care in this field. This study's objective was to create such a tool for Geriatric Evaluation and Management Units (GEMUs).</p> <p>Methods</p> <p>The methodology involved a reliability and feasibility study of a retrospective chart review on 934 older inpatients admitted in 49 GEMUs during the year 2002–2003 for fall-related trauma as a tracer condition. Pertinent indicators for a chart abstraction tool, the Geriatric Care Tool (GCT), were developed and validated according to five dimensions: access to care, comprehensiveness, continuity of care, patient-centred care and appropriateness. Consensus methods were used to develop the content. Participants were experts representing eight main health care professions involved in GEMUs from 19 different sites. Items associated with high quality of care at each step of the multidisciplinary management of patients admitted due to falls were identified. The GCT was tested for intra- and inter-rater reliability using 30 medical charts reviewed by each of three independent and blinded trained nurses. Kappa and agreement measures between pairs of chart reviewers were computed on an item-by-item basis.</p> <p>Results</p> <p>Three quarters of 169 items identifying the process of care, from the case history to discharge planning, demonstrated good agreement (kappa greater than 0.40 and agreement over 70%). Indicators for the appropriateness of care showed less reliability.</p> <p>Conclusion</p> <p>Content validity and reliability results, as well as the feasibility of the process, suggest that the chart abstraction tool can gather standardized and pertinent clinical information for further evaluating quality of care in GEMU using admission due to falls as a tracer condition. However, the GCT should be evaluated in other models of acute geriatric units and new strategies should be developed to improve reliability of peer assessments in characterizing the quality of care for elderly patients with complex conditions.</p

Cognitive reserve and Alzheimer's disease biomarkers are independent determinants of cognition

The objective of this study was to investigate how a measure of educational and occupational attainment, a component of cognitive reserve, modifies the relationship between biomarkers of pathology and cognition in Alzheimer's disease. The biomarkers evaluated quantified neurodegeneration via atrophy on magnetic resonance images, neuronal injury via cerebral spinal fluid t-tau, brain amyloid-β load via cerebral spinal fluid amyloid-β1–42 and vascular disease via white matter hyperintensities on T2/proton density magnetic resonance images. We included 109 cognitively normal subjects, 192 amnestic patients with mild cognitive impairment and 98 patients with Alzheimer's disease, from the Alzheimer's Disease Neuroimaging Initiative study, who had undergone baseline lumbar puncture and magnetic resonance imaging. We combined patients with mild cognitive impairment and Alzheimer's disease in a group labelled ‘cognitively impaired’ subjects. Structural Abnormality Index scores, which reflect the degree of Alzheimer's disease-like anatomic features on magnetic resonance images, were computed for each subject. We assessed Alzheimer's Disease Assessment Scale (cognitive behaviour section) and mini-mental state examination scores as measures of general cognition and Auditory–Verbal Learning Test delayed recall, Boston naming and Trails B scores as measures of specific domains in both groups of subjects. The number of errors on the American National Adult Reading Test was used as a measure of environmental enrichment provided by educational and occupational attainment, a component of cognitive reserve. We found that in cognitively normal subjects, none of the biomarkers correlated with the measures of cognition, whereas American National Adult Reading Test scores were significantly correlated with Boston naming and mini-mental state examination results. In cognitively impaired subjects, the American National Adult Reading Test and all biomarkers of neuronal pathology and amyloid load were independently correlated with all cognitive measures. Exceptions to this general conclusion were absence of correlation between cerebral spinal fluid amyloid-β1–42 and Boston naming and Trails B. In contrast, white matter hyperintensities were only correlated with Boston naming and Trails B results in the cognitively impaired. When all subjects were included in a flexible ordinal regression model that allowed for non-linear effects and interactions, we found that the American National Adult Reading Test had an independent additive association such that better performance was associated with better cognitive performance across the biomarker distribution. Our main conclusions included: (i) that in cognitively normal subjects, the variability in cognitive performance is explained partly by the American National Adult Reading Test and not by biomarkers of Alzheimer's disease pathology; (ii) in cognitively impaired subjects, the American National Adult Reading Test, biomarkers of neuronal pathology (structural magnetic resonance imaging and cerebral spinal fluid t-tau) and amyloid load (cerebral spinal fluid amyloid-β1–42) all independently explain variability in general cognitive performance; and (iii) that the association between cognition and the American National Adult Reading Test was found to be additive rather than to interact with biomarkers of Alzheimer's disease pathology

Non-Stationarity in the “Resting Brain’s” Modular Architecture

Task-free functional magnetic resonance imaging (TF-fMRI) has great potential for advancing the understanding and treatment of neurologic illness. However, as with all measures of neural activity, variability is a hallmark of intrinsic connectivity networks (ICNs) identified by TF-fMRI. This variability has hampered efforts to define a robust metric of connectivity suitable as a biomarker for neurologic illness. We hypothesized that some of this variability rather than representing noise in the measurement process, is related to a fundamental feature of connectivity within ICNs, which is their non-stationary nature. To test this hypothesis, we used a large (n = 892) population-based sample of older subjects to construct a well characterized atlas of 68 functional regions, which were categorized based on independent component analysis network of origin, anatomical locations, and a functional meta-analysis. These regions were then used to construct dynamic graphical representations of brain connectivity within a sliding time window for each subject. This allowed us to demonstrate the non-stationary nature of the brain’s modular organization and assign each region to a “meta-modular” group. Using this grouping, we then compared dwell time in strong sub-network configurations of the default mode network (DMN) between 28 subjects with Alzheimer’s dementia and 56 cognitively normal elderly subjects matched 1∶2 on age, gender, and education. We found that differences in connectivity we and others have previously observed in Alzheimer’s disease can be explained by differences in dwell time in DMN sub-network configurations, rather than steady state connectivity magnitude. DMN dwell time in specific modular configurations may also underlie the TF-fMRI findings that have been described in mild cognitive impairment and cognitively normal subjects who are at risk for Alzheimer’s dementia

Magnetic resonance spectroscopy, β-amyloid load, and cognition in a population-based sample of cognitively normal older adults

Objective: To determine the relationship between proton magnetic resonance spectroscopy (1H MRS) metabolites and β-amyloid (Aβ) load and the effects of Aβ load on the association between 1H MRS metabolites and cognitive function in cognitively normal older adults. Methods: We studied 311 cognitively normal older adults who participated in the populationbased Mayo Clinic Study of Aging from January 2009 through September 2010. Participants underwent 11C-Pittsburgh compound B (PiB) PET, 1H MRS from the posterior cingulate gyri, and neuropsychometric testing to assess memory, attention/executive, language, and visual-spatial domain functions within 6 months. Partial Spearman rank order correlations were adjusted for age, sex, and education. Results: Higher PiB retention was associated with abnormal elevations in myoinositol (mI)/creatine (Cr) (partial rs = 0.17; p = 0.003) and choline (Cho)/Cr (partial rs = 0.13; p = 0.022) ratios. Higher Cho/Cr was associated with worse performance on Auditory Verbal Learning Test Delayed Recall (partial rs = -0.12; p = 0.04), Trail Making Test Part B (partial rs = 0.12; p = 0.04), Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol (partial r s = -0.18; p \u3c 0.01), and WAIS-R Block Design (partial r s=-0.12; p = 0.03). Associations between 1H MRS metabolites and cognitive function were not different among participants with high vs low PiB retention. Conclusion: In cognitively normal older adults, the 1H MRS metabolite ratios mI/Cr and Cho/Cr are associated with the preclinical pathologic processes in the Alzheimer disease cascade. Higher Cho/Cr is associated with worse performance on domain-specific cognitive tests independent of Aβ load, suggesting that Cho/Cr elevation may also be dependent on other preclinical dementia pathologies characterized by Cho/Cr elevation such as Lewy body or ischemic vascular disease in addition to Aβ load. © 2011 by AAN Enterprises, Inc