Significance of Normalization on Anatomical MRI Measures in Predicting Alzheimer’s Disease

This study establishes a new approach for combining neuroimaging and neuropsychological measures for an optimal decisional space to classify subjects with Alzheimer’s disease (AD). This approach relies on a multivariate feature selection method with different MRI normalization techniques. Subcortical volume, cortical thickness, and surface area measures are obtained using MRIs from 189 participants (129 normal controls and 60 AD patients). Statistically significant variables were selected for each combination model to construct a multidimensional space for classification. Different normalization approaches were explored to gauge the effect on classification performance using a support vector machine classifier. Results indicate that theMini-mental state examination (MMSE) measure is most discriminative among single-measure models, while subcortical volume combined with MMSE is the most effective multivariate model for AD classification. The study demonstrates that subcortical volumes need not be normalized, whereas cortical thickness should be normalized either by intracranial volume ormean thickness, and surface area is a weak indicator of AD with and without normalization. On the significant brain regions, a nearly perfect symmetry is observed for subcortical volumes and cortical thickness, and a significant reduction in thickness is particularly seen in the temporal lobe, which is associated with brain deficits characterizing AD

Factors related to medication adherence in memory disorder clinic patients.

Medication adherence is a substantial problem in the elderly. It may be even more important among elderly persons with memory problems, since other factors that lead to non-adherence may be compounded with the memory problems themselves. The objective was to determine whether a model that integrates research on medication adherence from several research domains is useful in understanding adherence in elderly patients. The methodology involved a cross-sectional observational study using a convenience sample of 63 patients drawn from a university-affiliated outpatient memory disorders clinic. The primary measure of medication adherence was caregivers\u27 reports of patients\u27 medication adherence. Patients and their caregivers were asked questions assessing their beliefs about the seriousness of each condition for which a medication was prescribed and the likely outcome of that condition without treatment. Additional data collected included presence of side effects, total number of medications taken, and patients\u27 mood and cognitive status. Multilevel path analysis confirmed several model-based predictions. Caregivers\u27 reports of adherence were predicted by estimates of disease outcome, the presence of side effects, and patients\u27 relying on themselves to remember to take medications. Results partially confirm the integrative model in understanding medication adherence in these patients. Patients\u27 beliefs about the likely effect of medication treatment for their condition and the presence of side effects influence reported medication adherence. Results thus suggest that efforts to educate patients about the likely response of their medical condition to treatment and to assess and deal with medication side effects might improve patient adherence

Clinical characteristics of community-dwelling black Alzheimer\u27s disease patients.

There is a relative dearth of studies examining the cognitive and neuropsychiatric features of black Alzheimer\u27s disease (AD) patients in the United States. Therefore, this cross-sectional investigation reported on the prevalence and clinical correlates of depression and psychosis in a community-dwelling black AD sample. The study participants comprised 55 English-speaking black patients evaluated consecutively at a university-affiliated memory disorders clinic. All patients were evaluated utilizing standardized procedures and diagnosed with possible or probable AD according to the criteria established by the National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer\u27s Disease and Related Disorders Association. The presence of neuropsychiatric symptoms, including major depression and psychosis (delusions or hallucinations) was established via a semistructured psychiatric interview with the patient and primary care giver. The level of global cognitive impairment was rated with the Mini-Mental State Examination. The results showed that major depression and psychosis were observed in 20% and 58% of the sample, respectively. Mood disturbance was linked with low education, whereas psychosis was associated with greater cognitive dysfunction. This study provides important insight into the clinical characteristics of community-dwelling black AD patients. It is clear that continued research in the area of ethnicity and dementia is warranted to better understand the clinical needs of blacks and other minority populations in the United States that are afflicted with AD

Neuropathologic basis of frontotemporal dementia in progressive supranuclear palsy.

BackgroundProgressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by neuronal loss in the extrapyramidal system with pathologic accumulation of tau in neurons and glia. The most common clinical presentation of PSP, referred to as Richardson syndrome, is that of atypical parkinsonism with vertical gaze palsy, axial rigidity, and frequent falls. Although cognitive deficits in PSP are often ascribed to subcortical dysfunction, a subset of patients has dementia with behavioral features similar to the behavioral variant of frontotemporal dementia. In this study we aimed to identify the clinical and pathological characteristics of PSP presenting with frontotemporal dementia.MethodsIn this study, we compared clinical and pathologic characteristics of 31 patients with PSP with Richardson syndrome with 15 patients with PSP with frontotemporal dementia. For pathological analysis, we used semiquantitative methods to assess neuronal and glial lesions with tau immunohistochemistry, as well image analysis of tau burden using digital microscopic methods.ResultsWe found greater frontal and temporal neocortical neuronal tau pathology in PSP with frontotemporal dementia compared with PSP with Richardson syndrome. White matter tau pathology was also greater in PSP with frontotemporal dementia than PSP with Richardson syndrome. Genetic and demographic factors were not associated with atypical distribution of tau pathology in PSP with frontotemporal dementia.ConclusionsThe results confirm the subset of cognitive-predominant PSP mimicking frontotemporal dementia in PSP. PSP with frontotemporal dementia has distinct clinical features that differ from PSP with Richardson syndrome, as well as differences in distribution and density of tau pathology. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

A practical guideline for intracranial volume estimation in patients with Alzheimer’s disease

Background Intracranial volume (ICV) is an important normalization measure used in morphometric analyses to correct for head size in studies of Alzheimer Disease (AD). Inaccurate ICV estimation could introduce bias in the outcome. The current study provides a decision aid in defining protocols for ICV estimation in patients with Alzheimer disease in terms of sampling frequencies that can be optimally used on the volumetric MRI data, and the type of software most suitable for use in estimating the ICV measure. Methods Two groups of 22 subjects are considered, including adult controls (AC) and patients with Alzheimer Disease (AD). Reference measurements were calculated for each subject by manually tracing intracranial cavity by the means of visual inspection. The reliability of reference measurements were assured through intra- and inter- variation analyses. Three publicly well-known software packages (Freesurfer, FSL, and SPM) were examined in their ability to automatically estimate ICV across the groups. Results Analysis of the results supported the significant effect of estimation method, gender, cognitive condition of the subject and the interaction among method and cognitive condition factors in the measured ICV. Results on sub-sampling studies with a 95% confidence showed that in order to keep the accuracy of the interleaved slice sampling protocol above 99%, the sampling period cannot exceed 20 millimeters for AC and 15 millimeters for AD. Freesurfer showed promising estimates for both adult groups. However SPM showed more consistency in its ICV estimation over the different phases of the study. Conclusions This study emphasized the importance in selecting the appropriate protocol, the choice of the sampling period in the manual estimation of ICV and selection of suitable software for the automated estimation of ICV. The current study serves as an initial framework for establishing an appropriate protocol in both manual and automatic ICV estimations with different subject populations

Semantic Interference Deficits and the Detection of Mild Alzheimer’s Disease and Mild Cognitive Impairment Without Dementia

Impairment in delayed recall has traditionally been considered a hallmark feature of Alzheimer’s disease (AD). However, vulnerability to semantic interference may reflect early manifestations of the disorder. In this study, 26 mildly demented AD patients (mild AD), 53 patients with mild cognitive impairment without dementia (MCI), and 53 normal community-dwelling elders were first presented 10 common objects that were recalled over 3 learning trials. Subjects were then presented 10 new semantically related objects followed by recall for the original targets. After controlling for the degree of overall memory impairment, mild AD patients demonstrated greater proactive but equivalent retroactive interference relative to MCI patients. Normal elderly subjects exhibited the least amount of proactive and retroactive interference effects. Recall for targets susceptible to proactive interference correctly classified 81.3% of MCI patients and 81.3% of normal elderly subjects, outperforming measures of delayed recall and rate of forgetting. Adding recognition memory scores to the model enhanced both sensitivity (84.6%) and specificity (88.5%). A combination of proactive and retroactive interference measures yielded sensitivity of 84.6% and specificity of 96.2% in differentiating mild AD patients from normal older adults. Susceptibility to proactive semantic interference may be an early cognitive feature of MCI and AD patients presenting for clinical evaluation. (JINS, 2004, 10, 91–100.

The utility of age-specific cut-offs for visual rating of medial temporal atrophy in classifying Alzheimer\u27s disease, MCI and cognitively normal elderly subjects

Background: New research criteria for diagnosing Alzheimer\u27s disease (AD) in the mild cognitive impairment stage (MCI-AD) incorporate biomarkers to assign a level of certainty to the diagnosis. Structural MRI is widely available but greatly under-utilized for assessing atrophy of structures affected in early AD, such as the hippocampus (HP), because the quantification of HP volumes (HP-v) requires special expertise, and normative values have not been established. Methods: Elderly subjects (n = 273) from the Florida ADRC were classified as having no cognitive impairment (cognitively normal, CN), amnestic mild cognitive impairment (aMCI) or AD. Volumes for the hippocampus (HP-v) were measured on structural MRI scans. A validated visual rating system for measuring medial temporal atrophy (VRS-MTA), including hippocampal, entorhinal cortex and perirhinal cortex atrophy was employed. The participants were subdivided into younger (less than or equal to 75 years of age) and older (greater than 75 years of age) subgroups. Results: Volumetric and VRS-MTA measures were equivalent in predicting classification of CN vs. aMCI for older (area under the receiver operator curves [aROC]: 0.652 vs. 0.723) and younger subjects (aROC: 0.764 vs. 0.736). However, for younger AD subjects, aROC values were significantly higher for VRS-MTA measures (0.920) than for volumetric measures (0.847). Relative to HP-v, VRS-MTA score was significantly more correlated to impairment on a range of memory tests and was more associated with progression of aMCI to AD than HP-v. Conclusion: Structural MRI with VRS-MTA assessment can serve as a biomarker for supporting the diagnosis of MCI-AD. Age-adjusted VRS-MTA scores are at least as effective as HP-v for distinguishing aMCI and AD from CN and for predicting progression from aMCI to AD. VRS-MTA is convenient for use in the clinic as well as for clinical trials and can readily be incorporated into a standardized radiological report

Longitudinal Study on Oral Health in Subjects with Alzheimer's Disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111087/1/j.1532-5415.1994.tb06074.x.pd

Of Authenticity and Woman: Personal Narratives of Middle-Class Women in Modern China

Also CSST Working Paper #126.http://deepblue.lib.umich.edu/bitstream/2027.42/51317/1/553.pd