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Articles by David Loewenstein
Total Records ( 4 ) for David Loewenstein
  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.
  Denis A. Evans , Francine Grodstein , David Loewenstein , Jeffrey Kaye and Sandra Weintraub
  Dementia of the Alzheimer‘s type (DAT) is a major public health threat in developed countries where longevity has been extended to the eighth decade of life. Estimates of prevalence and incidence of DAT vary with what is measured, be it change from a baseline cognitive state or a clinical diagnostic endpoint, such as Alzheimer‘s disease. Judgment of what is psychometrically ”normal“ at the age of 80 years implicitly condones a decline from what is normal at the age of 30. However, because cognitive aging is very heterogeneous, it is reasonable to ask ”Is ’normal for age‘ good enough to screen for DAT or its earlier precursors of cognitive impairment?“ Cost containment and accessibility of ascertainment methods are enhanced by well-validated and reliable methods such as screening for cognitive impairment by telephone interviews. However, focused assessment of episodic memory, the key symptom associated with DAT, might be more effective at distinguishing normal from abnormal cognitive aging trajectories. Alternatively, the futuristic ”Smart Home,“ outfitted with unobtrusive sensors and data storage devices, permits the moment-to-moment recording of activities so that changes that constitute risk for DAT can be identified before the emergence of symptoms.
  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.
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