Faculty Bibliography

A variable poly-T polymorphism in the TOMM40 gene, which is in linkage disequilibrium with APOE, was recently implicated with increased risk and earlier onset age for late-onset Alzheimer's disease in APOE epsilon3 carriers. To elucidate potential neurobiological mechanisms underlying this association, we compared the effect of TOMM40 poly-T variants to the effect of APOE, an established LOAD-risk modulator, on cerebrospinal fluid (CSF) amyloid beta (Abeta) and tau levels, in cognitively intact elderly subjects. APOE epsilon4 carriers showed significant reductions in Abeta 1-42 levels compared to non-epsilon4 carriers, but no differences were detected across TOMM40 variants. Neither Abeta 1-40 nor tau levels were affected by APOE or TOMM40

PURPOSE: Advances in neurobiology are providing new opportunities to investigate the neurological systems underlying motor speech control. This study explores the perceptual characteristics of the speech of three genotypes of spino-cerebellar ataxia (SCA) as manifest in four different speech tasks. METHODS: Speech samples from 26 speakers with SCA were perceptually rated by experienced listeners. The genotypes were: SCA1, SCA5, or SCA6. The speech tasks were: diadochokinesis, word repetition, sentence reading, and picture description. The speech samples were rated using two sets of dimensions characterized as primary (e.g., articulation, rate, and rhythm) or secondary (e.g., imprecise consonants, excess and equal stress, and harsh voice). RESULTS: On primary dimensions, SCA6 was the most impaired generally. Articulation was the most severely affected dimension and the diadochokinesis task was most effective in revealing speech impairments. On secondary dimensions, picture description was the task most likely to produce abnormal speech. The SCA groups shared articulatory problems but differed with respect to abnormal voice features. CONCLUSIONS: These results support previous characterizations of ataxic dysarthria, and provide further information about the speech characteristics of genetic subtypes. Task demands affect perceptual ratings. Voice characteristics may be key to differentiating ataxic subtypes. As the genetic disorders that affect speech become better understood, more detailed characterizations of motor control systems should emerge. Learning outcomes The reader will: (1) be able to recognize the principle characteristics of ataxia; (2) recognize that not all speech tasks are equally sensitive to ataxic dysarthria; (3) recognize that voice quality changes may play an important role in recognizing different genetic types of ataxia

Introduction: An important goal of ongoing Alzheimer's disease (AD) research is to identify markers that allow one to predict risk for the development of this type of dementia in cognitively intact elderly. Known cognitive changes associated with AD, possibly reflecting hippocampal pathology, include a worse recall of primacy items and better immediate recall of items learned at the end of a list compared to the middle (recency effect). Aims: The aim of our study was to examine whether learning and recall of primacy and recency words predicted future decline in intact elderly subjects. Methods: Individuals with MMSE of 28 or over at baseline were included in the study. Of these, 211 had at least two successive cognitive evaluations; mean age at baseline was 69.5 (SD=8.0). We regressed MMSE decline on baseline Auditory-Verbal Learning Test (AVLT) memory measures, focusing especially on learning and recall of primacy and recency words, and controlling for baseline age, time since baseline and other variables. Results: Worse learning/delayed recall of primacy words on AVLT trials consistently predicted greater subsequent cognitive decline. Additionally, this effect was stronger among older subjects than among younger ones. APOE e4, a well established genetic risk factor for late-onset AD, was not a significant predictor of MMSE decline in this sample. Conclusions: Decreased learning and poorer recall of primacy words in the AVLT is a predictor of decline in healthy elderly individuals, and future studies should examine if decreased learning and recall can predict conversion to AD

Introduction: Subthalamic nucleus (STN) deep brain stimulation (

PURPOSE: Speaking, which naturally occurs in different modes or 'tasks' such as conversation and repetition, relies on intact basal ganglia nuclei. Recent studies suggest that voice and fluency parameters are differentially affected by speech task. In this study, the authors examine the effects of subcortical functionality on voice and fluency, comparing measures obtained from spontaneous and matched repeated speech samples. METHOD: Subjects with Parkinson's disease who were being treated with bilateral deep brain stimulation (DBS) of the subthalamic nuclei were tested with stimulators ON and OFF. RESULTS: The study found that a voice measure, harmonic to noise ratio, is improved in repetition and in the DBS-ON condition and that dysfluencies are more plentiful in conversation with little or variable influence of DBS condition. CONCLUSIONS: These findings suggest that voice and fluency are differentially affected by DBS treatment and that task conditions, interacting with subcortical functionality, influence motor speech performance