Blake K. Scanlon

A questionnaire-based (UM-PDHQ) study of hallucinations in Parkinson's disease

BackgroundHallucinations occur in 20–40% of PD patients and have been associated with unfavorable clinical outcomes (i.e., nursing home placement, increased mortality). Hallucinations, like other non-motor features of PD, are not well recognized in routine primary/secondary clinical practice. So far, there has been no instrument for uniform characterization of hallucinations in PD. To this end, we developed the University of Miami Parkinsons disease Hallucinations Questionnaire (UM-PDHQ) that allows comprehensive assessment of hallucinations in clinical or research settings.MethodsThe UM-PDHQ is composed of 6 quantitative and 14 qualitative items. For our study PD patients of all ages and in all stages of the disease were recruited over an 18-month period. The UPDRS, MMSE, and Beck Depression and Anxiety Inventories were used for comparisons.Results and DiscussionSeventy consecutive PD patients were included in the analyses. Thirty-one (44.3%) were classified as hallucinators and 39 as non-hallucinators. No significant group differences were observed in terms of demographics, disease characteristics, stage, education, depressive/anxiety scores or cognitive functioning (MMSE) between hallucinators and non-hallucinators. Single mode hallucinations were reported in 20/31 (visual/14, auditory/4, olfactory/2) whereas multiple modalities were reported in 11/31 patients. The most common hallucinatory experience was a whole person followed by small animals, insects and reptiles.ConclusionUsing the UM-PDHQ, we were able to define the key characteristics of hallucinations in PD in our cohort. Future directions include the validation of the quantitative part of the questionnaire than will serve as a rating scale for severity of hallucinations.

Pulse pressure in relation to tau-mediated neurodegeneration, cerebral amyloidosis, and progression to dementia in very old adults

IMPORTANCEnIncreased pulse pressure associated with age-related arterial stiffening increases risk for Alzheimer dementia but the mechanism responsible for this association remains unclear.nnnOBJECTIVESnTo determine the relationship between pulse pressure and cerebral spinal fluid biomarker profiles of preclinical Alzheimer disease, investigate whether observed relationships are stronger in adults with more advanced arterial age (≥80 years of age), and examine the relationship between pulse pressure and progression to dementia.nnnDESIGN, SETTING, AND PARTICIPANTSnIn this retrospective cohort study, 877 participants without dementia (55-91 years of age) from the Alzheimers Disease Neuroimaging Initiative underwent baseline health assessment, including blood pressure assessment and lumbar puncture for determination of cerebral spinal fluid phosphorylated tau (P-tau) and β-amyloid 1-42. Participants have been followed up longitudinally since 2005. The last date of examination was October 15, 2013. Clinical follow-up between 6 and 96 months tracked progression to dementia.nnnMAIN OUTCOMES AND MEASURESnRegression and analysis of covariance analyses investigated relationships between pulse pressure and distinct cerebral spinal fluid biomarker profiles. Very old participants (80 years or older) were compared with younger participants (55-79 years of age) on clinical measures and pulse pressure × age group interactions were investigated. Survival analysis examined the effect of baseline pulse pressure on progression to dementia. Covariates were age, sex, apolipoprotein E genotype, body mass index, vascular risk factors, and antihypertensive medication use.nnnRESULTSnIndividuals with a P-tau-positive biomarker profile exhibited mean (SD) elevated pulse pressure regardless of age (62.0 [15.6] mm Hg for a P-tau-positive biomarker vs 57.4 [14.0] mm Hg for P-tau-negative biomarker; P =u2009.04). In very old participants, a further increase in pulse pressure was observed in those exhibiting both P-tau elevation and β-amyloid 1-42 reduction vs either biomarkers alone (69.7 [16.0] mm Hg for both positive biomarkers vs 63.18 [13.0] mm Hg for P-tau alone vs 60.1 [16.4] mm Hg for β-amyloid 1-42 alone vs 56.6 [14.5] mm Hg for negative biomarkers; P = .003). Those with higher baseline pulse pressure progressed to dementia more rapidly (95% CI, 1.000-1.048; P = .05; hazard ratio = 1.024). Systolic pressure exhibited similar relationships with Alzheimer disease biomarkers and progression to dementia in the very old subgroup (P < .05) but showed no associations in the young old subgroup (P > .10). Diastolic pressure was reduced in young old participants with isolated phosphorylated tau elevation (P = .04).nnnCONCLUSIONS AND RELEVANCEnPulse pressure, an index of vascular aging, was associated with neurodegenerative change prior to the onset of dementia across a broad age range. Among those with more advanced age, higher pulse pressure was also associated with cerebral amyloidosis in the presence of neurodegeneration and more rapid progression to dementia. Diastolic contributions to these biomarker associations were limited to young old participants whereas systolic contributions were found only in very old participants.

Objective Quantification of Neuromotor Symptoms in Parkinson's Disease: Implementation of a Portable, Computerized Measurement Tool

Quantification of neuromotor symptoms with device-based measures provides a useful supplement to clinical evaluation. Research using the CATSYS has established its utility as a computerized measurement system to quantify neuromotor function. The primary objective of this study is to provide technical guidance on the use of the CATSYS in Parkinsons disease (PD). Forty-four patients with idiopathic PD and 28 healthy controls were prospectively recruited and evaluated with CATSYS, a portable, Windows-based system consisting of a data logger and four different sensors (tremor pen, touch recording plate, reaction time handle, and force plate for balance recording) for quantification of neuromotor functions. CATSYS discriminated between PD and controls on measurements of rest/postural tremor, pronation/supination, finger tapping, simple reaction time, and postural sway intensity and velocity. CATSYS measurements using the proposed test battery were associated with relevant clinician-rated Unified Parkinsons disease rating scale (UPDRS) items assessing tremor and bradykinesia. More work is warranted to establish CATSYS as a diagnostic/monitoring instrument in movement disorders using the proposed technical approaches.

Whole-brain proton MR spectroscopic imaging in Parkinson's disease.

To examine the distributions of proton magnetic resonance spectroscopy (MRS) observed metabolites in Parkinsons disease (PD) throughout the whole brain.

APOE-epsilon4 and aging of medial temporal lobe gray matter in healthy adults older than 50 years.

Atrophy of the hippocampus and surrounding temporal regions occurs in Alzheimers disease (AD). APOE ε4, the major genetic risk factor for late-onset AD, has been associated with smaller volume in these regions before amyloidosis can be detected by AD biomarkers. To examine APOE ε4 effects in relation to aging, we performed a longitudinal magnetic resonance imaging study involving cognitively normal adults (25 APOE ε4 carriers and 31 ε3 homozygotes), initially aged 51-75 years. We used growth curve analyses, which can provide information about APOE ε4-related differences initially and later in life. Hippocampal volume was the primary outcome; nearby medial temporal regions were secondary outcomes. Brain-derived neurotrophic factor, val66met was a secondary covariate. APOE ε4 carriers had significantly smaller initial hippocampal volumes than ε3 homozygotes. Rate of hippocampal atrophy was not greater in the APOE ε4 group, although age-related atrophy was detected in the overall sample. The findings add to the growing evidence that effects of APOE ε4 on hippocampal size begin early in life, underscoring the importance of early interventions to increase reserve.

Modeling the effects of obstructive sleep apnea and hypertension in Vietnam veterans with PTSD

PurposeThe present work aimed to extend models suggesting that obstructive sleep apnea (OSA) is associated with worse cognitive performance in community-dwelling older adults. We hypothesized that in addition to indices of OSA severity, hypertension is associated with worse cognitive performance in such adults.MethodsThe PTSD Apnea Clinical Study recruited 120 community-dwelling, male veterans diagnosed with PTSD, ages 55 and older. The Rey Auditory Verbal Learning Test (RAVLT) and Color-Word Interference Test (CWIT) were measures of auditory verbal memory and executive function, respectively. Apnea–hypopnea index (AHI), minimum and mean pulse oximeter oxygen saturation (min SpO2, mean SpO2) indicators were determined during standard overnight polysomnography. Multivariate linear regression and receiver operating characteristic (ROC) curve analyses were performed.ResultsIn regression models, AHI (βu2009=u2009−4.099; pu2009<u20090.01) and hypertension (βu2009=u2009−4.500; pu2009<u20090.05) predicted RAVLT; hypertension alone (βu2009=u20099.146; pu2009<u20090.01) predicted CWIT. ROC analyses selected min SpO2 cut-points of 85% for RAVLT (κu2009=u20090.27; χ²u2009=u20098.23, pu2009<u20090.01) and 80% for CWIT (κu2009=u20090.25; χ²u2009=u200912.65, pu2009<u20090.01). Min SpO2 cut-points and hypertension were significant when added simultaneously in a regression model for RAVLT (min SpO2, βu2009=u20094.452; pu2009<u20090.05; hypertension, βu2009=u2009−4.332; pu2009<u20090.05), and in separate models for CWIT (min SpO2, βu2009=u2009−8.286; pu2009<u20090.05; hypertension, βu2009=u2009−8.993; pu2009<u20090.01).ConclusionsOSA severity and presence of self-reported hypertension are associated with poor auditory verbal memory and executive function in older adults.

Statistical analysis and mapping of the unified Parkinson’s Disease rating scale to Hoehn and Yahr staging

* Asterisk denotes corresponding author. Affiliations: 1 Systems Analysis, Modelling and Prediction (SAMP), Department of Engineering Science, University of Oxford, Oxford, UK 2 Oxford Centre for Industrial and Applied Mathematics (OCIAM), University of Oxford, Oxford, UK 3 Media Lab, Massachusetts Institute of Technology, Cambridge, MA, USA 4 Smith School of Enterprise and the Environment, University of Oxford, Oxford, UK 5 Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA 6 Sierra-Pacific Mental Illness Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA, USA 7 Department of Neurology, Miller School of Medicine, University of Miami, USA

An accelerometry-based study of lower and upper limb tremor in Parkinson’s disease

Over the past two decades, several studies have aimed to quantify the kinetic properties of tremor with primary focus on the upper limbs. However, there is a lack of investigation into the properties of tremor in the lower limbs. The objective of this preliminary study was to investigate the properties of oscillatory movement, at rest and in posture, in both the upper and lower limbs of Parkinsons disease (PD) patients with clinically undetectable to modest rest/postural tremor and healthy controls. PD patients (N = 16) and controls (N = 8) were examined clinically by a movement disorders specialist and oscillatory movements in all four extremities were evaluated using a portable biaxial accelerometer. While tremor intensity and frequency did not differ between groups, the intraindividual variability of rest and postural tremor frequency in the dexterity-dominant lower limb was lower in people living with PD than in healthy adults. Additionally, rest tremor frequency was discrepant between upper and lower limbs in PD. Our work introduces the possibility that minute variations in lower limb movements, which are imperceptible upon expert clinical exam, can be used to differentiate a diseased sample from a healthy one. These preliminary findings suggest that additional work using objective tremor measurement may improve our understanding of lower limb motor dysfunction in PD and lead to the refinement of current, and the development of new, metrics to enhance early diagnosis, differential diagnosis, and symptom quantification.

Subthreshold depression in Parkinson’s disease

It is estimated that 40% of patients with Parkinsons disease (PD) are clinically depressed, however, little is known about the frequency and associated features of subthreshold depression in PD. The current study sought to determine the prevalence of subthreshold depression (sD) and to further characterize the associated features in a sample of 111 nondemented patients with moderate to severe PD.

Initial Cognitive Performance Predicts Longitudinal Aviator Performance

OBJECTIVESnThe goal of the study was to improve prediction of longitudinal flight simulator performance by studying cognitive factors that may moderate the influence of chronological age.nnnMETHODnWe examined age-related change in aviation performance in aircraft pilots in relation to baseline cognitive ability measures and aviation expertise. Participants were aircraft pilots (N = 276) aged 40-77.9. Flight simulator performance and cognition were tested yearly; there were an average of 4.3 (± 2.7; range 1-13) data points per participant. Each participant was classified into one of the three levels of aviation expertise based on Federal Aviation Administration pilot proficiency ratings: least, moderate, or high expertise.nnnRESULTSnAddition of measures of cognitive processing speed and executive function to a model of age-related change in aviation performance significantly improved the model. Processing speed and executive function performance interacted such that the slowest rate of decline in flight simulator performance was found in aviators with the highest scores on tests of these abilities. Expertise was beneficial to pilots across the age range studied; however, expertise did not show evidence of reducing the effect of age.nnnDISCUSSIONnThese data suggest that longitudinal performance on an important real-world activity can be predicted by initial assessment of relevant cognitive abilities.