Impact of Aphasia on Brain Activation to Motor Commands in Patients with Acute Intracerebral Hemorrhage.

BACKGROUND: Brain activation to motor commands is seen in 15% of clinically unresponsive patients with acute brain injury. This state called cognitive motor dissociation (CMD) is detectable by electroencephalogram (EEG) or functional magnetic resonance imaging, predicts long-term recovery, and is recommended by recent guidelines to support prognostication. However, false negative CMD results are a particular concern, and occult aphasia in clinically unresponsive patients may be a major factor. This study aimed to quantify the impact of aphasia on CMD testing. METHODS: We prospectively studied 61 intensive care unit patients admitted with acute primary intracerebral hemorrhage (ICH) who had behavioral evidence of command following or were able to mimic motor commands. All patients underwent an EEG-based motor command paradigm used to detect CMD and comprehensive aphasia assessments. Logistic regression was used to identify predictors of brain activation, including aphasia types and associations with recovery of independence (Glasgow Outcome Scale-Extended score ≥ 4). RESULTS: Of 61 patients, 50 completed aphasia and the EEG-based motor command paradigm. A total of 72% (n = 36) were diagnosed with aphasia. Patients with impaired comprehension (i.e., receptive or global aphasia) were less likely to show brain activation than those with intact comprehension (odds ratio [OR] 0.23 [95% confidence interval 0.05-0.89], p = 0.04). Brain activation was independently associated with Glasgow Outcome Scale-Extended ≥ 4 by 12 months (OR 2.4 [95% confidence interval 1.2-5.0], p = 0.01) accounting for the Functional Outcome in Patients with Primary ICH score (OR1.3 [95% confidence interval 1.0-1.8], p = 0.01). CONCLUSIONS: Brain activation to motor commands is four times less likely for patients with primary ICH with impaired comprehension. False negative results due to occult receptive aphasia need to be considered when interpreting CMD testing. Early detection of brain activation may help predict long-term recovery in conscious patients with ICH.

Brain artery diameters and risk of dementia and stroke.

INTRODUCTION: We tested the association of brain artery diameters with dementia and stroke risk in three distinct population-based studies using conventional T2-weighted brain magnetic resonance imaging (MRI) images. METHODS: We included 8420 adults > 40 years old from three longitudinal population-based studies with brain MRI scans. We estimated and meta-analyzed the hazard ratios (HRs) of the brain and carotids and basilar diameters associated with dementia and stroke. RESULT: Overall and carotid artery diameters > 95th percentile increased the risk for dementia by 1.74 (95% confidence interval [CI], 1.13-2.68) and 1.48 (95% CI, 1.12-1.96) fold, respectively. For stroke, meta-analyses yielded HRs of 1.59 (95% CI, 1.04-2.42) for overall arteries and 2.11 (95% CI, 1.45-3.08) for basilar artery diameters > 95th percentile. DISCUSSION: Individuals with dilated brain arteries are at higher risk for dementia and stroke, across distinct populations. Our findings underline the potential value of T2-weighted brain MRI-based brain diameter assessment in estimating the risk of dementia and stroke.

Relationships of hematocrit concentration with dementia from a multiethnic population-based study.

OBJECTIVE: Red blood cell (RBC) concentration impacts cerebrovascular disease, yet it is unclear whether RBC concentrations relate to dementia risk, particularly in racially/ethnically diverse cohorts. We investigated whether RBC concentrations associate with incident dementia risk in a diverse population of stroke-free individuals and explored whether cerebral small vessel disease (CSVD) mediates this relationship. METHODS: A longitudinal observational analysis was performed using a population-based cohort of stroke-free, older adult participants (>50 years) from the Northern Manhattan Study (NOMAS) enrolled between 2003-2008. Participants received baseline hematocrit testing, MRI neuroimaging, and cognitive assessments at baseline and long-term follow-up. Associations of baseline hematocrit as a categorical variable (low, normal [reference], and high based on laboratory reference levels) with incident dementia were assessed using Cox models adjusting for relevant covariates. Separate analyses investigated whether MRI CSVD mediated these relationships. RESULTS: We studied 1207 NOMAS participants (mean age 71±9 years, 60% female, 66% Hispanic). Mean hematocrit was 41.2% (±3.8) with 16% of participants developing incident dementia. Lower hematocrit associated with increased dementia risk (adjusted hazard ratio 1.81 [1.01-3.23]) after adjusting for age, sex, race/ethnicity, education, APOE status, and comorbidities. High hematocrit was not associated with dementia risk. No interactions by sex or race/ethnicity were seen and baseline CSVD did not mediate relationships between hematocrit and dementia. CONCLUSIONS: Low hematocrit associated with dementia risk in our diverse population cohort. Further work is needed to assess mechanisms behind anemia's relationship with dementia to assess whether this can serve as a trackable, preventable/treatable risk factor for dementia.

The effects of long-term interferon-beta-1b treatment on cognitive functioning in multiple sclerosis: a 16-year longitudinal study.

BACKGROUND: Multiple sclerosis (MS) is a progressive disease of the central nervous system that affects cognition. Short-term treatment with interferon-beta-1b (IFN-b-1b) has been shown to have beneficial effects on cognition. OBJECTIVE: The objective of this paper is to evaluate the effects of IFN-b-1b on cognitive functioning in patients with MS over the course of 16 years. METHODS: Sixteen subjects with relapsing-remitting MS participated in the study. Nine of these subjects received IFN-b-1b, while seven received placebo treatment in the pivotal MS trial. After five years, all subjects were switched to IFN-b-1b treatment. At two and four years into the study, all subjects underwent a brief neuropsychological test battery, magnetic resonance imaging (MRI), and neurologic ratings; measures were repeated at 16 years. RESULTS: Across the total cohort, cognitive functioning remained relatively stable over the course of 16 years. The placebo/IFN-b-b group exhibited increased visual memory performance relative to the IFN-b-1b treatment group, but had a greater decline in verbal memory. Initial MRI lesion load demonstrated a significant, negative correlation with overall cognitive performance at 16 years (p = 0.00). CONCLUSION: We conclude that IFN-b-1b has beneficial effects on long-term cognition outcomes in MS.

Differential role of dopamine in emotional attention and memory: evidence from Parkinson's disease.

Consistent with the hypothesis that dopamine is implicated in the processing of salient stimuli relevant to the modification of various behavioral responses, Parkinson's disease is associated with emotional blunting. To address the hypothesis that emotional attention and memory are modulated by dopaminergic neurotransmission in Parkinson's disease, we assessed 15 nondemented patients with Parkinson's disease while on and off dopaminergic medication and 15 age-matched healthy controls. Visual stimuli were presented, and recognition was used to assess emotional memory. Response latency was used as a measure of emotional attention modulation. Stimuli were varied based on valence (pleasant, neutral, and unpleasant) and arousal (high and low) dimensions. Controls had significantly better memory for positive than negative stimuli, whereas patients with Parkinson's disease tested off medication had significantly better memory for negative than positive items. This negativity bias was lost when they were tested while on dopaminergic medication. Reaction times in patients with Parkinson's disease off medication were longer than in healthy controls and, paradoxically, were even longer when on medication. Further, although both healthy controls and patients with Parkinson's disease in the "off" state had arousal-induced prolongation of reaction time, this effect was not seen in patients with Parkinson's disease on medication. These data indicate that dopaminergic neurotransmission is implicated in emotional memory and attention and suggest that dopamine mediates emotional memory via the valence dimension and emotional attention via arousal. Furthermore, our findings suggest that emotional changes in Parkinson's disease result from the effects of both the disease process and dopaminergic treatment.

Preserved emotional modulation of motor response time despite psychomotor slowing in young-old adults.

Whereas aging affects cognitive and psychomotor processes negatively, the impact of aging on emotional processing is less clear. Using an "old-new" binary decision task, we ascertained the modulation of response latencies after presentation of neutral and emotional pictures in "young" (M = 27.1 years) and "young-old" adults with a mean age below 60 (M = 57.7 years). Stimuli varied on valence (pleasant, neutral, and unpleasant) and arousal (high and low) dimensions. Young-old adults had significantly longer reaction times. However, young and young-old adults showed the exact same pattern of response time modulation by emotional stimuli: Response latencies were longer for high-arousal than for low-arousal pictures and longer for negative than for positive or neutral stimuli. This result suggests that the specific effects of implicitly processed emotional valence and arousal information on behavioral response time are preserved in young-old adults despite significant age-related psychomotor decline.

Race/Ethnic Disparities in Mild Cognitive Impairment and Dementia: The Northern Manhattan Study.

BACKGROUND: Variability in dementia rates across racial and ethnic groups has been estimated at 60%. Studies suggest disparities in Caribbean Hispanic and Black populations, but community-based data are limited. OBJECTIVE: Estimate the prevalence of mild cognitive impairment (MCI) and dementia in the racially and ethnically diverse community-based Northern Manhattan Study cohort and examine sociodemographic, vascular risk factor, and brain imaging correlates. METHODS: Cases of MCI and dementia were adjudicated by a team of neuropsychologists and neurologists and prevalence was estimated across race/ethnic groups. Ordinal proportional odds models were used to estimate race/ethnic differences in the prevalence of MCI or dementia adjusting for sociodemographic variables (model 1), model 1 plus potentially modifiable vascular risk factors (model 2), and model 1 plus structural imaging markers of brain integrity (model 3). RESULTS: There were 989 participants with cognitive outcome determinations (mean age 69±9 years; 68% Hispanic, 16% Black, 14% White; 62% women; mean (±SD) follow-up five (±0.6) years). Hispanic and Black participants had greater likelihood of MCI (20%) and dementia (5%) than White participants accounting for age and education differences. Hispanic participants had greater odds of MCI or dementia than both White and Black participants adjusting for sociodemographic variables, vascular risk factors, and brain imaging factors. White matter hyperintensity burden was significantly associated with greater odds of MCI or dementia (OR = 1.3, 1.1 to 1.6), but there was no significant interaction by race/ethnicity. CONCLUSION: In this diverse community-based cohort, cross-sectional data revealed significant race/ethnic disparities in the prevalence of MCI and dementia. Longer follow-up and incidence data are needed to further clarify these relationships.

Features of gait most responsive to tap test in normal pressure hydrocephalus.

OBJECTIVE: To identify components of gait associated with a positive tap test (TT) in patients with idiopathic normal pressure hydrocephalus (iNPH). PATIENTS AND METHODS: Thirty-three patients with iNPH underwent clinical evaluation pre- and post-TT and were classified as responders (Rs) or non-responders (NRs). Elements of gait were assessed with a formal standardized Gait Scale and compared between groups. RESULTS: Analysis of pre/post-TT group differences revealed an interaction for Total Gait Score and Walking Score, with improvements in responders only. Total Gait Scores improved by 29% in the Rs and 4.85% in the NRs. Rs showed significant post-TT improvements on a timed 10m walk, turning, and balance. Tandem walking, turning, truck balance and start stop hesitation showed trends toward improvement. CONCLUSIONS: The classic features of gait often used in determining diagnosis of NPH (wide based stride, reduced foot-floor clearance, and small steps) were not helpful in identifying responders to the TT. Walking speed, steps for turning, and tendency towards falling were most likely to improve post-TT. These straightforward measures can readily be adapted into clinical practice to assist in determination of shunt candidacy.

Childhood Learning Disabilities and Atypical Dementia: A Retrospective Chart Review.

OBJECTIVE: To further our understanding of the association between self-reported childhood learning disabilities (LDs) and atypical dementia phenotypes (Atypical Dementia), including logopenic primary progressive aphasia (L-PPA), Posterior Cortical Atrophy (PCA), and Dysexecutive-type Alzheimer's Disease (AD). METHODS: This retrospective case series analysis of 678 comprehensive neuropsychological assessments compared rates of self-reported LD between dementia patients diagnosed with Typical AD and those diagnosed with Atypical Dementia. 105 cases with neuroimaging or CSF data available and at least one neurology follow-up were identified as having been diagnosed by the neuropsychologist with any form of neurodegenerative dementia. These cases were subject to a consensus diagnostic process among three dementia experts using validated clinical criteria for AD and PPA. LD was considered Probable if two or more statements consistent with prior LD were documented within the Social & Developmental History of the initial neuropsychological evaluation. RESULTS: 85 subjects (Typical AD n=68, Atypical AD n=17) were included in the final analysis. In logistic regression models adjusted for age, gender, handedness, education and symptom duration, patients with Probable LD, compared to patients without Probable LD, were significantly more likely to be diagnosed with Atypical Dementia vs. Typical AD (OR 13.1, 95% CI 1.3-128.4). All three of the L-PPA cases reporting a childhood LD endorsed childhood difficulty with language. By contrast, both PCA cases reporting Probable childhood LD endorsed difficulty with attention and/or math. CONCLUSIONS: In people who develop dementia, childhood LD may predispose to atypical phenotypes. Future studies are required to confirm whether atypical neurodevelopment predisposes to regional-specific neuropathology in AD and other dementias.

Postshunt cognitive and functional improvement in idiopathic normal pressure hydrocephalus.

BACKGROUND: Improvement in gait after shunt placement has been well documented in idiopathic normal pressure hydrocephalus (iNPH); however, controversy remains regarding the extent and pattern of postsurgical cognitive changes. Conflicting findings may be explained by variability in both test selection and follow-up intervals across studies. Furthermore, most investigations lack a control group, making it difficult to disentangle practice effects from a true treatment effect. OBJECTIVE: To examine postshunt changes in a sample of well-characterized iNPH participants compared with a group of age- and education-matched healthy control subjects. METHODS: We identified 12 participants with iNPH undergoing shunt placement and 9 control participants. All participants were evaluated with comprehensive neuropsychological testing and standardized gait assessment at baseline and were followed up for 6 months. RESULTS: Repeated-measures analysis of variance revealed a significant group- (iNPH and control) by-time (baseline and 6 months) interaction for Trailmaking Test B: (P < .003) and Symbol Digit Modalities (P < .02), with greater improvement in iNPH participants relative to control subjects. In addition, the iNPH group showed greater improvement in gait (P < .001) and caregivers reported improved activities of daily living (P < .01) and reduced caregiver distress (P < .01). CONCLUSION: This study demonstrates improvements in mental tracking speed and sustained attention 6 months after shunt placement in iNPH. The present investigation is the first study to use a controlled design to show that cognitive improvement in iNPH is independent of practice effects. Furthermore, these findings indicate functional and quality-of-life improvements for both the shunt responder and their caregiver.

Unattended emotional intonations modulate linguistic prosody processing.

Prosody or speech melody subserves linguistic (e.g., question intonation) and emotional functions in speech communication. Findings from lesion studies and imaging experiments suggest that, depending on function or acoustic stimulus structure, prosodic speech components are differentially processed in the right and left hemispheres. This direct current (DC) potential study investigated the linguistic processing of digitally manipulated pitch contours of sentences that carried an emotional or neutral intonation. Discrimination of linguistic prosody was better for neutral stimuli as compared to happily as well as fearfully spoken sentences. Brain activation was increased during the processing of happy sentences as compared to neutral utterances. Neither neutral nor emotional stimuli evoked lateralized processing in the left or right hemisphere, indicating bilateral mechanisms of linguistic processing for pitch direction. Acoustic stimulus analysis suggested that prosodic components related to emotional intonation, such as pitch variability, interfered with linguistic processing of pitch course direction.