Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) can probe tissue biochemistry with high resolution and sensitivity without requiring exogenous contrast agents. Applying CEST MRI at ultrahigh field provides advantages of increasing spectral resolution and improving sensitivity to metabolites with faster proton exchange rates such as glutamate, a critical neurotransmitter in the brain. Prior magnetic resonance spectroscopy and CEST MRI studies have revealed altered regulation of glutamate in patients with multiple sclerosis (MS).

Olfactory and Neuropsychological Functioning in Olfactory Reference Syndrome.

Background: Olfactory reference syndrome (ORS) is an underrecognized, understudied, and often severe psychiatric disorder characterized by a prominent and distressing or impairing preoccupation with a false belief of emitting an offensive body odor. As this condition has only recently been recognized in the International Classification of Diseases (the 11th Edition), no empirical evidence exists about the underlying features and etiology of the disorder.

Objective: To examine the neuropsychological and olfactory functioning of individuals with ORS and address whether there is central nervous system or sensory dysfunction associated with the condition.

Data quality assurance and control in cognitive research: Lessons learned from the PREDICT-HD study.

We discuss the strategies employed in data quality control and quality assurance for the cognitive core of Neurobiological Predictors of Huntington's Disease (PREDICT-HD), a long-term observational study of over 1,000 participants with prodromal Huntington disease. In particular, we provide details regarding the training and continual evaluation of cognitive examiners, methods for error corrections, and strategies to minimize errors in the data. We present five important lessons learned to help other researchers avoid certain assumptions that could potentially lead to inaccuracies in their cognitive data.

The impact of oculomotor functioning on neuropsychological performance in Huntington disease.

Huntington disease (HD) is a neurodegenerative condition with prominent motor (including oculomotor), cognitive, and psychiatric effects. While neuropsychological deficits are present in HD, motor impairments may impact performance on neuropsychological measures, especially those requiring a speeded response, as has been demonstrated in multiple sclerosis and schizophrenia. The current study is the first to explore associations between oculomotor functions and neuropsychological performance in HD.

Intra-individual Variability in Prodromal Huntington Disease and Its Relationship to Genetic Burden.

The current study sought to examine the utility of intra-individual variability (IIV) in distinguishing participants with prodromal Huntington disease (HD) from nongene-expanded controls. IIV across 15 neuropsychological tasks and within-task IIV using a self-paced timing task were compared as a single measure of processing speed (Symbol Digit Modalities Test [SDMT]) in 693 gene-expanded and 191 nongene-expanded participants from the PREDICT-HD study. After adjusting for depressive symptoms and motor functioning, individuals estimated to be closest to HD diagnosis displayed higher levels of across- and within-task variability when compared to controls and those prodromal HD participants far from disease onset (F ICV(3,877)=11.

Distinguishing Alzheimer's disease and dementia with Lewy bodies using cognitive and olfactory measures.

Objective: Given poor sensitivity of the diagnostic criteria in identifying dementia with Lewy bodies (DLB), the use of cognitive and olfactory measures to distinguish Alzheimer's disease (AD) from DLB was assessed.

Method: Twenty-six patients with DLB and 60 patients with AD were administered several cognitive measures and the Brief Smell Identification Task (BSIT).

Result: Patients with DLB performed significantly worse on the BSIT and visuoconstruction tasks than patients with AD, but significantly better on delayed recall of a word list.

Dementia in multiple sclerosis: why is it rarely discussed?

Cognitive deficits in multiple sclerosis (MS) have been well studied in decades of MS research. Severe deficits are acknowledged, but the frequency is minimized in the literature, and there is a striking lack of discussion of the presence of a dementia state in MS. Possible reasons for this omission are discussed, along with an argument to define the dementia state and to provide terminology that will be palatable to patients.

Speedy eye movements in multiple sclerosis: association with performance on visual and nonvisual cognitive tests.

Objective: Eye movement difficulties in multiple sclerosis (MS) are common and may influence performance on cognitive tests. The following studies examined associations between a new measure of speedy eye movement speed and visual/nonvisual cognitive tests.

Method: In Experiment 1, MS patients (N = 71) were administered cognitive tests and the Speedy Eyes Test (SET) as a measure of purposeful speedy eye movements under timed conditions.

Prediction of manifest Huntington's disease with clinical and imaging measures: a prospective observational study.

Background: Although the association between cytosine-adenine-guanine (CAG) repeat length and age at onset of Huntington's disease is well known, improved prediction of onset would be advantageous for clinical trial design and prognostic counselling. We compared various measures for tracking progression and predicting conversion to manifest Huntington's disease.

Methods: In this prospective observational study, we assessed the ability of 40 measures in five domains (motor, cognitive, psychiatric, functional, and imaging) to predict time to motor diagnosis of Huntington's disease, accounting for CAG repeat length, age, and the interaction of CAG repeat length and age.

Clinical and Biomarker Changes in Premanifest Huntington Disease Show Trial Feasibility: A Decade of the PREDICT-HD Study.

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.

Cognitive reserve and brain reserve in prodromal Huntington's disease.

Huntington disease (HD) is associated with decline in cognition and progressive morphological changes in brain structures. Cognitive reserve may represent a mechanism by which disease-related decline may be delayed or slowed. The current study examined the relationship between cognitive reserve and longitudinal change in cognitive functioning and brain volumes among prodromal (gene expansion-positive) HD individuals.

Normative performance on the Brief Smell Identification Test (BSIT) in a multi-ethnic bilingual cohort: a Project FRONTIER study.

The Brief Smell Identification Test (BSIT) is a commonly used measure of olfactory functioning in elderly populations. Few studies have provided normative data for this measure, and minimal data are available regarding the impact of sociodemographic factors on test scores. This study presents normative data for the BSIT in a sample of English- and Spanish-speaking Hispanic and non-Hispanic Whites.

Regional atrophy associated with cognitive and motor function in prodromal Huntington disease.

Background: Neuroimaging studies suggest that volumetric MRI measures of specific brain structures may serve as excellent biomarkers in future clinical trials of Huntington disease (HD).

Objective: Demonstration of the clinical significance of these measures is an important step in determining their appropriateness as potential outcome measures.

Methods: Measures of gray- and white-matter lobular volumes and subcortical volumes (caudate, putamen, globus pallidus, thalamus, nucleus accumbens, hippocampus) were obtained from MRI scans of 516 individuals who tested positive for the HD gene expansion, but were not yet exhibiting signs or symptoms severe enough to warrant diagnosis ("pre-HD").

Measuring executive dysfunction longitudinally and in relation to genetic burden, brain volumetrics, and depression in prodromal Huntington disease.

Executive dysfunction (ED) is a characteristic of Huntington disease (HD), but its severity and progression is less understood in the prodromal phase, e.g., before gross motor abnormalities.

Depressive symptom severity is related to poorer cognitive performance in prodromal Huntington disease.

Objective: Depression is associated with more severe cognitive deficits in many neurological disorders, though the investigation of this relationship in Huntington disease (HD) has been limited. This study examined the relationship between depressive symptom severity and measures of executive functioning, learning/memory, and attention in prodromal HD.

Method: Participants (814 prodromal HD, 230 gene-negative) completed a neuropsychological test battery and the Beck Depression Inventory-II (BDI-II).

Unemployment in multiple sclerosis: the contribution of personality and disease.

Background: Multiple sclerosis (MS) is the leading cause of neurological disability among young and middle-aged adults. One of the most devastating consequences of MS in this relatively young population group is unemployment. Although certain demographic and disease factors have been associated with employment, few studies have examined the contribution of person-specific factors, such as personality.

Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis.

Objectives: The goal of this study was to determine if memory would be improved by donepezil as compared to placebo in a multicenter, double-blind, randomized clinical trial (RCT).

Methods: Donepezil 10 mg daily was compared to placebo to treat memory impairment. Eligibility criteria included the following: age 18-59 years, clinically definite multiple sclerosis (MS), and performance ≤ ½ SD below published norms on the Rey Auditory Verbal Learning Test (RAVLT).

Comparison of verbal memory impairment rates in mild cognitive impairment.

There are no accepted guidelines establishing the most sensitive neuropsychological methods to define memory impairment in mild cognitive impairment (MCI). We investigated whether similar impairment rates were observed between the Hopkins Verbal Learning Test-Revised (HVLT-R) and Logical Memory (LM) in 90 patients with amnestic or amnestic plus MCI. On HVLT-R delayed recall, 80% of participants performed in the MCI range compared to only 32.

On becoming a peer reviewer for a neuropsychology journal.

The peer-review process is an invaluable service provided by the professional community, and it provides the critical foundation for the advancement of science. However, there is remarkably little systematic guidance for individuals who wish to become part of this process. This paper, written from the perspective of reviewers and editors with varying levels of experience, provides general guidelines and advice for new reviewers in neuropsychology, as well as outlining benefits of participation in this process.

Common blood laboratory values are associated with cognition among older inpatients referred for neuropsychological testing.

The purpose of this study was to examine the relationship between common laboratory values and cognitive functioning among 129 inpatients referred for neuropsychological evaluation. Laboratory values were recorded at admission, at the time point closest to neuropsychological evaluation, and at the time of peak metabolic derangement. Cognitive status was evaluated with the modified Mini-Mental State Exam.

Odor identification in mild cognitive impairment subtypes.

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.

Burden among spousal and child caregivers of patients with mild cognitive impairment.

Background/aims: Patients with mild cognitive impairment (MCI) experience cognitive declines and often report significant emotional/behavioral changes. Despite this, few studies have examined the impact of MCI on caregiver burden. The purpose of this study was to confirm the presence of caregiver burden in MCI and examine the relationship between burden and patients' neuropsychological, behavioral and emotional functioning.

Neuropsychological correlates of self-reported depression and self-reported cognition among patients with mild cognitive impairment.

Patients with mild cognitive impairment (MCI) frequently experience significant depressive symptomatology and report cognitive disturbances. To date, no studies have examined the relationship between MCI patients' neuropsychologic functioning, self-reported depressive symptoms, and self-reported cognitive difficulties. In this study, 82 MCI patients completed a comprehensive neuropsychological evaluation that included the Beck Depression Inventory (BDI).

Odor identification deficits in frontotemporal dementia: a preliminary study.

Multiple neurodegenerative disorders (e.g. Alzheimer's disease, Dementia with Lewy bodies, Parkinson's disease, and Huntington's disease) show olfactory deficits.

Boston naming performance distinguishes between Lewy body and Alzheimer's dementias.

Although naming impairment is common among persons with dementia, little is known about how specific error types on naming tasks may differ between dementias. Recent research has suggested that persons with dementia with Lewy bodies (DLB) have more visuospatial/visuoperceptual dysfunction than those with Alzheimer's disease (AD), which may impact their ability to correctly perceive and name objects. Our retrospective study evaluated the presence and frequency of error types among patients with DLB and AD on the Boston Naming Test (BNT).