Holly James Westervelt

There is growing consensus that intervention and treatment of Huntington disease (HD) should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural history of the disease and a dearth of appropriate outcome measures. Objectives of the current study are to document the natural history of premanifest HD progression in the largest cohort ever studied and to develop a battery of imaging and clinical markers of premanifest HD progression that can be used as outcome measures in preventive clinical trials. PREDICT-HD is a 32-site, international, observational study of premanifest HD, with annual examination of 1013 participants with premanifest HD and 301 gene-expansion negative controls between 2001 and 2012. Findings document 39 variables representing imaging, motor, cognitive, functional, and psychiatric domains, showing different rates of decline between premanifest Huntington disease and controls. Required sample size and models of premanifest HD are presented to inform future design of clinical and preclinical research. Preventive clinical trials in premanifest HD with participants who have a medium or high probability of motor onset are calculated to be as resource-effective as those conducted in diagnosed HD and could interrupt disease seven to twelve years earlier. Methods and measures for preventive clinical trials in premanifest HD more than a dozen years from motor onset are also feasible. These findings represent the most thorough documentation of a clinical battery for experimental therapeutics in stages of premanifest HD, the time period for which effective intervention may provide the most positive possible outcome for patients and their families affected by this devastating disease.

The current study examined odor identification using the Brief Smell Identification Test (BSIT) in mild cognitive impairment (MCI) subtypes (17 “amnestic MCI”, 46 “amnestic-plus MCI”, and 25 “MCI other”). Performance in participants with MCI was compared to that of participants with Alzheimer's disease (AD, n = 44) and healthy elderly (n = 21). MCI participants performed worse than controls, but better than those with AD. MCI subtypes did not differ. The magnitude of difference between MCI participants and controls was modest, raising some question of the clinical utility of the BSIT in early detection of MCI and early differential diagnosis.

To assess perceptions of the neuropsychological evaluation, 349 patients and 218 significant others presenting to an academic medical center neuropsychology service were surveyed over a two year period. Thirty-seven percent of the patient surveys (n = 129) and 37% of the significant other surveys (n = 80) were returned. Overall, both patients and significant others reported being satisfied with the interview, testing, and feedback sessions. Responders were generally receptive to the recommendations made, but were more inclined to have followed recommendations regarding patient safety (63.6%) than coping or support (31.8%). Some barriers to compliance with recommendations were identified.

Odor identification deficits are frequently reported in Alzheimer's disease (AD) but are not universal. This study examines differences in clinical p

The relationship between odor identification and cognition has not been previously well characterized. The neuroanatomy of the olfactory system and the frequent finding of olfactory dysfunction in neurodegenerative diseases suggest a likely relationship between odor identification and memory, language, and executive functioning, though previous studies have often failed to demonstrate the expected relationship. The current study examined this relationship in across a continuum of ability levels (N=100). Strongest correlations were found between odor identification and language, most aspects of memory, and a measure of general cognitive functioning. Significant but more modest correlations were seen between odor identification and attention, motor, visuospatial, and executive functions. A regression analysis revealed language as the only significant predictor of olfactory performance. These findings suggest that odor identification is most closely associated with other measures of temporo-limbic functioning. The implications of these findings, particularly in consideration of the assessment of older adults, are discussed.

To describe odor identification performance in patients with diffuse Lewy body disease and determine the clinical utility of odor identification tests in distinguishing diffuse Lewy body disease from Alzheimer disease. The presence of olfactory deficits, especially odor identification deficits, has been well established in both Alzheimer disease and Parkinson disease. The presence of olfactory deficits in diffuse Lewy body disease is also likely given the overlap of clinical symptoms and neuropathology with Alzheimer disease and Parkinson disease. However, odor identification abilities have not been described previously in diffuse Lewy body disease. Nine patients from a clinic sample with diffuse Lewy body disease and nine carefully matched patients with Alzheimer disease were administered an odor identification task as part of their neuropsychologic evaluations. Patients with diffuse Lewy body disease performed significantly worse than patients with Alzheimer disease on the odor identification test. Odor identification deficits may be more prevalent and severe in people with diffuse Lewy body disease than in people with Alzheimer disease, and olfactory testing may be useful in antemortem differential diagnosis of the two disorders.