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Articles by Ranjan Duara
Total Records ( 6 ) for Ranjan Duara
  Ranjan Duara , Warren Barker , David Loewenstein and Lisa Bain
  At the Sixth Annual Mild Cognitive Impairment Symposium in Miami Beach, Florida, a multidisciplinary group of experts from the Alzheimer`s disease (AD) community met to discuss the current status of AD intervention trials and future plans for designing trials of prodromal AD and/or mild cognitive impairment. There is no agreement regarding a single pathogenic mechanism to be targeted, although a consensus seems to be emerging that effective treatment will require attacking multiple targets. These targets include beta amyloid (Aß) aggregates (including different isoforms and different aggregation species), neurofibrillary tangles composed of hyperphosphorylated tau, neuronal and synaptic loss, and mechanisms that contribute to Aß deposition–induced inflammation and immune dysregulation. Vascular disease, which is very common in the elderly, also appears to be a contributor to AD pathogenesis and might be modifiable through pharmacologic and lifestyle interventions to reduce the impact of conditions such as hypertension and metabolic syndrome. Potential disease-modifying approaches that were discussed, including pharmacologic agents that target Aβ, immunotherapy to eliminate plaques in the brain, passive immunotherapy, and secretase inhibitors. Nonpharmacologic approaches included stimulation of endogenous bone marrow cells, which can enter the brain and remove amyloid deposits, and cognitive and exercise training. Innovative trial designs are required that will allow a drug`s effectiveness to be determined efficiently in the transition from normal to mild cognitive impairment to probable AD. This might be achieved through the use of various forms of imaging and measurement of biochemical markers in the blood or cerebrospinal fluid, as well as measures that assess very early cognitive and behavioral changes. In the absence of effective treatments for AD, clinicians are faced with a dilemma about why, when, and how to disclose the diagnosis to patients and their family members and/or caregivers. The issues were discussed from multiple perspectives by a panel that included a lay representative, neurologist, psychiatrist, primary care physician, and a psychosocial researcher.
  David R. Weir , Robert B. Wallace , Kenneth M. Langa , Brenda L. Plassman , Robert S. Wilson , David A. Bennett , Ranjan Duara , David Loewenstein , Mary Ganguli and Mary Sano
  Establishing methods for ascertainment of dementia and cognitive impairment that are accurate and also cost-effective is a challenging enterprise. Large population-based studies often using administrative data sets offer relatively inexpensive and reliable estimates of severe conditions including moderate to advanced dementia that are useful for public health planning, but they can miss less severe cognitive impairment which may be the most effective point for intervention. Clinical and epidemiological cohorts, intensively assessed, provide more sensitive detection of less severe cognitive impairment but are often costly. In this article, several approaches to ascertainment are evaluated for validity, reliability, and cost. In particular, the methods of ascertainment from the Health and Retirement Study are described briefly, along with those of the Aging, Demographics, and Memory Study (ADAMS). ADAMS, a resource-intense sub-study of the Health and Retirement Study, was designed to provide diagnostic accuracy among persons with more advanced dementia. A proposal to streamline future ADAMS assessments is offered. Also considered are algorithmic and Web-based approaches to diagnosis that can reduce the expense of clinical expertise and, in some contexts, can reduce the extent of data collection. These approaches are intended for intensively assessed epidemiological cohorts where goal is valid and reliable case detection with efficient and cost-effective tools.
  David A. Loewenstein , Maria T. Greig , John A. Schinka , Warren Barker , Qian Shen , Elizabeth Potter , Ashok Raj , Larry Brooks , Daniel Varon , Michael Schoenberg , Jessica Banko , Huntington Potter and Ranjan Duara
  Background/Aims To investigate the clinical features and rates of progression of conditions that are not considered to be normal, but do not fulfill criteria for mild cognitive impairment (MCI). Methods We longitudinally evaluated 269 elderly subjects who did not meet formal criteria for MCI at baseline but had: (1) a clinical history suggesting MCI without neuropsychological deficits (PreMCI-Clinical); or (2) neuropsychological deficits on one or more memory measures in conjunction with a negative clinical examination (amnestic PreMCI-NP) or were normal on both neuropsychological and clinical examination. Results The rate of progression to MCI or dementia over an average of 2- to 3 years was 3.7% for no cognitive impairment subjects, whereas it was significantly greater for all PreMCI subtypes (22.0% for PreMCI-Clinical, 38.9% for amnestic PreMCI-NP subjects with two or more memory impairments). Among PreMCI subjects as a whole, lower baseline scores on object memory and category fluency tests were the best predictors of progression to MCI or dementia. Cardiovascular risk factors, Parkinsonian symptoms, and hippocampal atrophy were not associated with progression. Conclusion Distinct PreMCI subtypes defined on the basis of clinical and neuropsychological evaluations were found to have distinct characteristics, but both subtypes demonstrated elevated risk for progression to MCI or dementia. Despite the lack of evidence of clinical impairment, subjects with neuropsychological deficits in two memory domains were particularly at increased risk for progression of their deficits.
  Miriam Jocelyn Rodriguez , Elizabeth Potter , Qian Shen , Warren Barker , Maria Greig- Custo , Joscelyn Agron , David Loewenstein and Ranjan Duara
  Objective To assess medial temporal atrophy (MTA) and atrophy adjacent to the third ventricle (Peri-IIIVent) on brain magnetic resonance images as biomarkers for the diagnosis of Alzheimer‘s disease (AD) and Lewy body dementia (LBD), and to assess the relationship between biomarkers and clinical and functional measures. Methods Subjects diagnosed with no cognitive impairment (n = 30), AD (n = 30), or LBD (n = 31) were evaluated with the Mini-Mental State Examination, Multiple Delayed Recall Test, Category Fluency Test, Clinical Dementia Rating Sum of Boxes score, Functional Assessment Questionnaire, and the Unified Parkinson‘s Disease Rating Scale. A validated visual rating system was used to rate MTA, and volumetric studies were performed to measure total intracranial and hippocampal volumes. Additionally, linear measurements of third ventricle width, Peri-IIIVent height, and Peri-IIIVent width were performed. Results Subjects with AD and those with LBD were equivalent with respect to age and levels of cognitive impairment. Atrophy in medial temporal and Peri-IIIVent regions was greater among both patients with AD and those with LBD compared with subjects with no cognitive impairment. The best discriminators of AD from LBD were the severity of MTA, using visual rating, and the severity of memory impairment. Only subjects with LBD showed significant correlations between Unified Parkinson‘s Disease Rating Scale scores and Peri-IIIVent atrophy measures. Conclusions Mild AD could be distinguished from mild LBD by the severity of MTA and memory impairment. The severity of parkinsonism was associated with the severity of atrophy in the third ventricular region, but was not a good discriminator between AD and LBD.
  Qian Shen , Weizhao Zhao , David A. Loewenstein , Elizabeth Potter , Maria T. Greig , Ashok Raj , Warren Barker , Huntington Potter and Ranjan Duara
  Background The segmentation of brain structures on magnetic resonance imaging scans for calculating regional brain volumes, using automated anatomic labeling, requires the use of both brain atlases and templates (template sets). This study aims to improve the accuracy of volumetric analysis of hippocampus (HP) and amygdala (AMG) in the assessment of early Alzheimer‘s disease (AD) by developing template sets that correspond more closely to the brains of elderly individuals. Methods Total intracranial volume and HP and AMG volumes were calculated for elderly subjects with no cognitive impairment (n = 103), with amnestic mild cognitive impairment (n = 68), or with probable AD (n = 46) using the following: (1) a template set consisting of a standard atlas (atlas S), drawn on a young adult male brain, and the widely used Montreal Neurological Institute template (MNI template set); (2) a template set (template S set) in which the template is based on smoothing the image from which atlas S is derived; and (3) a new template set (template E set) in which the template is based on an atlas (atlas E) created from the brain of an elderly individual. Results Correspondence to HP and AMG volumes derived from manual segmentation was highest with automated segmentation by template E set, intermediate with template S set, and lowest with the MNI template set. The areas under the receiver operating curve for distinguishing elderly subjects with no cognitive impairment from elderly subjects with amnestic mild cognitive impairment or probable AD and the correlations between HP and AMG volumes and cognitive and functional scores were highest for template E set, intermediate for template S set, and lowest for the MNI template set. Conclusions The accuracy of automated anatomic labeling and the diagnostic value of the derived volumes are improved with template sets based on brain atlases closely resembling the anatomy of the to-be-segmented brain magnetic resonance imaging scans.
  Ranjan Duara , David A. Loewenstein , Qian Shen , Warren Barker , Elizabeth Potter , Daniel Varon , Kristen Heurlin , Rik Vandenberghe and Christopher Buckley
  Objective To evaluate the contributions of amyloid-positive (Am+) and medial temporal atrophy–positive (MTA+) scans to the diagnostic classification of prodromal and probable Alzheimer‘s disease (AD). Methods 18F-flutemetamol-labeled amyloid positron emission tomography (PET) and magnetic resonance imaging (MRI) were used to classify 10 young normal, 15 elderly normal, 20 amnestic mild cognitive impairment (aMCI), and 27 AD subjects. MTA+ status was determined using a cut point derived from a previous study, and Am+ status was determined using a conservative and liberal cut point. Results The rates of MRI scans with positive results among young normal, elderly normal, aMCI, and AD subjects were 0%, 20%, 75%, and 82%, respectively. Using conservative cut points, the rates of Am+ scans for these same groups of subjects were 0%, 7%, 50%, and 93%, respectively, with the aMCI group showing the largest discrepancy between Am+ and MTA+ scans. Among aMCI cases, 80% of Am+ subjects were also MTA+, and 70% of amyloid-negative (Am−) subjects were MTA+. The combination of amyloid PET and MTA data was additive, with an overall correct classification rate for aMCI of 86%, when a liberal cut point (standard uptake value ratio = 1.4) was used for amyloid positivity. Interpretation 18F-flutemetamol PET and structural MRI provided additive information in the diagnostic classification of aMCI subjects, suggesting an amyloid-independent neurodegenerative component among aMCI subjects in this sample.
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