Longitudinal hippocampal subfields, CSF biomarkers, and cognition in patients with Parkinson disease.

Objective: Hippocampal atrophy is an indicator of emerging dementia in PD, though it is unclear whether cerebral spinal fluid (CSF) Abeta-42, t-tau, or alpha-syn predict hippocampal subfield atrophy in a cohort of PD patients. To examine whether levels of CSF alpha-synuclein (alpha-syn), beta-amyloid 1-42 (Abeta-42) or total-tau (t-tau) are associated with hippocampal subfield volumes over time.

Methods: We identified a subset of Parkinson's Progression Markers Initiative (PPMI) PD patients with longitudinal T1-weighted imaging (baseline plus at least two additional visits across 12, 24, and 48 months) and CSF biomarkers available at baseline.

Blood-brain barrier disruption measured by albumin index correlates with inflammatory fluid biomarkers.

Blood-brain barrier (BBB) permeability can be measured by the ratio of albumin in cerebrospinal fluid (CSF) and blood and by dynamic contrast-enhanced MRI (DCEMRI). Albumin is a large molecule measured in CSF and blood to form the albumin index (Q), which is a global measure of BBB permeability, while the smaller Gadolinium molecule measures regional transfer (K); few studies have directly compared them in the same patients. We used both methods as part of a study of mechanisms of white matter injury in patients with different forms of dementia.

A double-dichotomy clustering of dual pathology dementia patients.

Introduction: Subcortical ischemic vascular disease (SIVD) and Alzheimer's disease (AD) related dementia can coexist in older subjects, leading to mixed dementia (MX). Identification of dementia sub-groups is important for designing proper treatment plans and clinical trials.

Method: An Alzheimer's disease severity (ADS) score and a vascular disease severity (VDS) score are calculated from CSF and MRI biomarkers, respectively.

Using a GPS Watch to Characterize Life-Space Mobility in Dementia: A Dyadic Case Study.

Persons with dementia (PWD) often experience difficulty navigating their environments and performing out-of-home activities. Life-space mobility (LSM) is an effective way of assessing functional levels and independence. We present a dyadic case study to explore the feasibility of using a global positioning system (GPS) watch to measure LSM of a Latino PWD.

Inflammatory Biomarkers Aid in Diagnosis of Dementia.

Dual pathology of Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID) commonly are found together at autopsy, but mixed dementia (MX) is difficult to diagnose during life. Biological criteria to diagnose AD have been defined, but are not available for vascular disease. We used the biological criteria for AD and white matter injury based on MRI to diagnose MX.

MarkVCID cerebral small vessel consortium: I. Enrollment, clinical, fluid protocols.

The concept of vascular contributions to cognitive impairment and dementia (VCID) derives from more than two decades of research indicating that (1) most older individuals with cognitive impairment have post mortem evidence of multiple contributing pathologies and (2) along with the preeminent role of Alzheimer's disease (AD) pathology, cerebrovascular disease accounts for a substantial proportion of this contribution. Contributing cerebrovascular processes include both overt strokes caused by etiologies such as large vessel occlusion, cardioembolism, and embolic infarcts of unknown source, and frequently asymptomatic brain injuries caused by diseases of the small cerebral vessels. Cerebral small vessel diseases such as arteriolosclerosis and cerebral amyloid angiopathy, when present at moderate or greater pathologic severity, are independently associated with worse cognitive performance and greater likelihood of dementia, particularly in combination with AD and other neurodegenerative pathologies.

A Multimodal Approach to Stratification of Patients with Dementia: Selection of Mixed Dementia Patients Prior to Autopsy.

Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID) are major causes of dementia, and when combined lead to accelerated cognitive loss. We hypothesized that biomarkers of neurodegeneration and neuroinflammation could be used to stratify patients into diagnostic groups. Diagnosis of AD can be made biologically with detection of amyloid and tau proteins in the cerebrospinal fluid (CSF) and vascular disease can be identified with diffusion tensor imaging (DTI).

MEG biomarker of Alzheimer's disease: Absence of a prefrontal generator during auditory sensory gating.

Magnetoencephalography (MEG), a direct measure of neuronal activity, is an underexplored tool in the search for biomarkers of Alzheimer's disease (AD). In this study, we used MEG source estimates of auditory gating generators, nonlinear correlations with neuropsychological results, and multivariate analyses to examine the sensitivity and specificity of gating topology modulation to detect AD. Our results demonstrated the use of MEG localization of a medial prefrontal (mPFC) gating generator as a discrete (binary) detector of AD at the individual level and resulted in recategorizing the participant categories in: (1) controls with mPFC generator localized in response to both the standard and deviant tones; (2) a possible preclinical stage of AD participants (a lower functioning group of controls) in which mPFC activation was localized to the deviant tone only; and (3) symptomatic AD in which mPFC activation was not localized to either the deviant or standard tones.

Brain structure and verbal function across adulthood while controlling for cerebrovascular risks.

The development and decline of brain structure and function throughout adulthood is a complex issue, with cognitive aging trajectories influenced by a host of factors including cerebrovascular risk. Neuroimaging studies of age-related cognitive decline typically reveal a linear decrease in gray matter (GM) volume/density in frontal regions across adulthood. However, white matter (WM) tracts mature later than GM, particularly in regions necessary for executive functions and memory.

The neuropathology and cerebrovascular mechanisms of dementia.

The prevalence of dementia is increasing in our aging population at an alarming rate. Because of the heterogeneity of clinical presentation and complexity of disease neuropathology, dementia classifications remain controversial. Recently, the National Plan to address Alzheimer’s Disease prioritized Alzheimer’s disease-related dementias to include: Alzheimer’s disease, dementia with Lewy bodies, frontotemporal dementia, vascular dementia, and mixed dementias.

Validation of biomarkers in subcortical ischaemic vascular disease of the Binswanger type: approach to targeted treatment trials.

Objectives: Vascular cognitive impairment (VCI) is a heterogeneous group of cerebrovascular diseases secondary to large and small vessel disease. We hypothesised that biomarkers obtained early in the disease could identify a homogeneous subpopulation with small vessel disease.

Methods: We obtained disease markers in 62 patients with VCI that included neurological findings, neuropsychological tests, multimodal MR and cerebrospinal fluid measurements of albumin ratio, matrix metalloproteinases (MMPs), amyloid-β1-42 and phosphorylated-τ181.

Same task, different strategies: how brain networks can be influenced by memory strategy.

Previous functional neuroimaging studies demonstrated that different neural networks underlie different types of cognitive processing by engaging participants in particular tasks, such as verbal or spatial working memory (WM) tasks. However, we report here that even when a WM task is defined as verbal or spatial, different types of memory strategies may be used to complete it, with concomitant variations in brain activity. We developed a questionnaire to characterize the type of strategy used by individual members in a group of 28 young healthy participants (18-25 years) during a spatial WM task.

Modulatory role of the prefrontal generator within the auditory M50 network.

The amplitude variability of the M50 component of neuromagnetic responses is commonly used to explore the brain's ability to modulate its response to incoming repetitive or novel auditory stimuli, a process conceptualized as a gating mechanism. The goal of this study was to identify the spatial and temporal characteristics of the cortical sources underlying the M50 network evoked by tones in a passive oddball paradigm. Twenty elderly subjects [10 patients diagnosed with mild cognitive impairment (MCI) or probable Alzheimer disease (AD) and 10 age-matched controls] were examined using magnetoencephalographic (MEG) recordings and the multi-dipole Calibrated Start Spatio-Temporal (CSST) source localization method.

Characterization of a normal control group: are they healthy?

We examined the health of a control group (18-81years) in our aging study, which is similar to control groups used in other neuroimaging studies. The current study was motivated by our previous results showing that one third of the elder control group had moderate to severe white matter hyperintensities and/or cortical volume loss which correlated with poor performance on memory tasks. Therefore, we predicted that cardiovascular risk factors (e.

Development and decline of memory functions in normal, pathological and healthy successful aging.

Many neuroimaging studies of age-related memory decline interpret resultant differences in brain activation patterns in the elderly as reflecting a type of compensatory response or regression to a simpler state of brain organization. Here we review a series of our own studies which lead us to an alternative interpretation, and highlights a couple of potential confounds in the aging literature that may act to increase the variability of results within age groups and across laboratories. From our perspective, level of cognitive functioning achieved by a group of elderly is largely determined by the health of individuals within this group.

Aging-related changes in auditory and visual integration measured with MEG.

As noted in the aging literature, processing delays often occur in the central nervous system with increasing age, which is often attributable in part to demyelination. In addition, differential slowing between sensory systems has been shown to be most discrepant between visual (up to 20ms) and auditory systems (<5ms). Therefore, we used MEG to measure the multisensory integration response in auditory association cortex in young and elderly participants to better understand the effects of aging on multisensory integration abilities.

Choice of initial antiepileptic drug for older veterans: possible pharmacokinetic drug interactions with existing medications.

Objectives: To identify clinically meaningful potential drug-drug interactions (PDIs) with antiepileptic drugs (AEDs), the AEDs and co-administered drugs commonly associated with AED-PDIs, and characteristics of patients with high likelihood of AED-PDI exposure.

Design: Five-year retrospective cohort study of veterans with new-onset epilepsy.

Setting: National Veterans Affairs and Medicare databases.

Somatosensory responses in normal aging, mild cognitive impairment, and Alzheimer's disease.

As a part of a larger study of normal aging and Alzheimer's disease (AD), which included patients with mild cognitive impairment (MCI), we investigated the response to median nerve stimulation in primary and secondary somatosensory areas. We hypothesized that the somatosensory response would be relatively spared given the reported late involvement of sensory areas in the progression of AD. We applied brief pulses of electric current to left and right median nerves to test the somatosensory response in normal elderly (NE), MCI, and AD.

Different strategies for auditory word recognition in healthy versus normal aging.

To explore the effects of commonly encountered pathology on auditory recognition strategies in elderly participants, magnetoencephalographic (MEG) brain activation patterns and performance were examined in 30 elderly [18 controls and 12 elderly with mild cognitive impairment (MCI) or probable Alzheimer's disease (AD)]. It was predicted that participants with known pathology would reveal different networks of brain activation, compared to healthy elderly, which should correlate with poorer performance. Participants heard a list of words representing common objects, twice.

New-onset epilepsy risk factors in older veterans.

Objectives: To identify risk factors for new-onset geriatric epilepsy that may trigger clinicians to consider a differential diagnosis of epilepsy at symptom onset.

Design: Retrospective cohort study.

Setting: National Veterans Affairs (VA) databases.

New-onset geriatric epilepsy care: Race, setting of diagnosis, and choice of antiepileptic drug.

Purpose: There is a growing movement to assess the quality of care provided to patients in the US, but few studies have examined initial care for epilepsy patients. We examined the relationships among patient race, setting of initial diagnosis, and initial treatment for older veterans newly diagnosed with epilepsy.

Methods: We used Department of Veterans Affairs (VA) inpatient, outpatient, pharmacy and Medicare data (1999-2004) to identify patients 66 years and older with new-onset epilepsy.

Trends in antiepileptic drug prescribing for older patients with new-onset epilepsy: 2000-2004.

Background: Newer antiepileptic drugs (AEDs) have been shown to be equally efficacious as older seizure medications but with fewer neurotoxic and systemic side effects in the elderly. A growing body of clinical recommendations based on systematic literature review and expert opinion advocate the use of the newer agents and avoidance of phenobarbital and phenytoin. This study sought to determine if changes in practice occurred between 2000 and 2004--a time during which evidence and recommendations became increasingly available.

What constitutes high quality of care for adults with epilepsy?

Background: Providers are increasingly being held accountable for the quality of care provided. While quality indicators have been used to benchmark the quality of care for a number of other disease states, no such measures are available for evaluating the quality of care provided to adults with epilepsy. In order to assess and improve quality of care, it is critical to develop valid quality indicators.