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1.  Dynamics of hemispheric dominance for language assessed by magnetoencephalographic imaging 
Annals of Neurology  2012;71(5):668-686.
The goal of the current study was to examine the dynamics of language lateralization using magnetoencephalographic (MEG) imaging, to determine the sensitivity and specificity of MEG-imaging, and to determine if MEG-imaging can become a viable alternative to the intracarotid amobarbital procedure (IAP), the current gold-standard for preoperative language lateralization in neurosurgical candidates.
MEG was recorded during an auditory verb-generation task and imaging analysis of oscillatory activity was initially performed in 21 subjects with epilepsy, brain tumor, or arteriovenous malformation who had undergone IAP and MEG. Time-windows and brain regions-of-interest that best discriminated between IAP determined left or right dominant for language were identified. Parameters derived in the retrospective analysis, was applied to a prospective cohort of 14 patients and healthy controls.
Power decreases in the beta-frequency band were consistently observed following auditory stimulation in inferior frontal, superior temporal, and parietal cortices; similar power decreases were also seen in inferior frontal cortex prior to and during overt verb generation. Language lateralization was clearly observed to be a dynamic process that is bilateral for several hundred milliseconds during periods of auditory perception and overt speech production. Correlation with the IAP was seen in 13 of 14 (93%) of prospective patients, with the test demonstrating a sensitivity of 100% and specificity of 92%.
Our results demonstrate excellent correlation between MEG imaging findings with the IAP for language lateralization, and provide new insights into the spatiotemporal dynamics of cortical speech processing.
PMCID: PMC3380661  PMID: 22522481
language lateralization; magnetoencephalography; verb generation; epilepsy surgery
2.  Driving Scenes test of the Neuropsychological Assessment Battery (NAB) and on-road driving performance in aging and very mild dementia 
The Driving Scenes test of the new Neuropsychological Assessment Battery (NAB; [Stern, R.A., & White, T. (2003a). Neuropsychological Assessment Battery. Lutz, FL: Psychological Assessment Resources, Inc.]) measures several aspects of visual attention thought to be important for driving ability. The current study examined the relationship between scores on the Driving Scenes test and on-road driving performance on a standardized driving test. Healthy participants performed significantly better on the Driving Scenes test than did very mildly demented participants. A correlation of 0.55 was found between the brief, office-based Driving Scenes test and the 108-point on-road driving score. Furthermore, the Driving Scenes test scores differed significantly across the driving instructor’s three global ratings (safe, marginal, and unsafe), and results of a discriminant function analysis indicated that the Driving Scenes test correctly classified 66% of participants into these groups. Thus, the new NAB Driving Scenes test appears to have good ecological validity for real-world driving ability in normal and very mildly demented older adults.
PMCID: PMC3292213  PMID: 15708731
Driving; Aging; Dementia; Neuropsychology; Attention; Visual
3.  Standardized measurement of self-awareness deficits in FTD and AD 
Diminished ability to perceive one’s own impairments, whether cognitive or social, is common in dementia, in particular frontotemporal dementia (FTD), where “lack of insight” is listed as a core diagnostic feature. Yet, there is no currently accepted method for measuring insight in dementia. The most commonly used methods, which involve comparing patients’ opinions of their level of impairment with the opinions of caregivers or close family members, are subjective and require the participation of a knowledgeable informant. Here, we introduce a new method that allows objective quantification of an individual’s awareness of their cognitive abilities and relies upon objective bedside testing.
We administered several tests of everyday, real-world functions to patients with FTD (n=10), Alzheimer’s disease (AD, n=10) and to control subjects (n=10). Prior to the tasks, participants were asked to predict their performance using a percentile-based rating system. They were also asked to estimate their performance after task completion. Differences between their self-rated and actual performances were calculated.
Whereas the control group showed very little discrepancy between pre-test predictions, post-task estimates and actual performance (mean difference of 3.9 percentile points for prediction /3.0 percentile points for post-task estimate), both patient groups over-predicted and overestimated their performance, with a significantly greater discrepancy for FTD (49.0/54.3 percentile points) than AD (27.2/28.3 percentile points).
Failures of insight and self-awareness of cognitive dysfunction can be objectively measured in dementia without the assistance of an informant, which will facilitate further study of this key component of higher cognitive functioning.
PMCID: PMC2820148  PMID: 19204020
Frontotemporal lobar degeneration; Alzheimer’s disease; Self-awareness; Insight
4.  Longitudinal Changes in Memory and Executive Functioning are Associated with Longitudinal Change in Instrumental Activities of Daily Living in older adults 
The Clinical neuropsychologist  2008;23(3):446-461.
Impaired everyday function is a diagnostic criterion for dementia, and a determinant of healthcare utilization and caregiver burden. Although many previous studies have demonstrated a cross-sectional relationships between cognition (particularly executive functions and memory) and everyday function in older adults, very little is known about longitudinal relationships between these domains. This study examined the association between longitudinal change in episodic memory (MEM) and executive functioning (EXEC) and change in everyday function. Participants were a cognitively heterogeneous group of 100 elderly persons including those with normal cognition, as well as those with mild cognitive impairment and dementia. They were followed for an average of five years. Random effects modeling showed that change in both MEM and EXEC were independently associated with rate of change in informant-rated instrumental activities of daily living (IADLs), even after controlling for age, education, and gender. Findings indicate that declines in MEM and EXEC over time make unique and independent contributions to declines in older adults’ ability to function in daily life.
PMCID: PMC2881703  PMID: 18821181
Memory; Executive functioning; Everyday Function; dementia; Alzheimer’s disease
5.  MCI is Associated With Deficits in Everyday Functioning 
The purpose of the present study was to examine the types of impairments in everyday function that accompany mild cognitive impairment (MCI). Data for this study was collected from 434 individuals consecutively evaluated at a university-based Alzheimer’s Center. A total of 96 participants were diagnosed with MCI, 105 were cognitively normal, and 233 had dementia. Informant ratings of participants’ abilities were obtained across different functional domains reflecting everyday abilities related to memory, language, visual spatial abilities, planning, organization, and divided attention. As expected, the demented group was significantly more impaired than the healthy control and MCI groups across all of the functional domains. The MCI group also showed significantly more functional impairment relative to healthy controls in all of the functional domains. Examination of the effect sizes as a measure of the magnitude of functional impairment in the MCI groups relative to controls showed that the greatest degree of impairment occurred within the Everyday Memory domain. The current findings suggest that individuals with MCI demonstrate deficits in a wide range of everyday functions but that the magnitude of these changes is greatest for those functional abilities that rely heavily on memory.
PMCID: PMC2880610  PMID: 17132965
mild cognitive impairment (MCI); dementia; functional impairment
6.  Cognitive and neuroimaging predictors of instrumental activities of daily living 
Impaired ability to conduct daily activities is a diagnostic criterion for dementia and a determinant of healthcare services utilization and caregiver burden. What predicts decline in instrumental activities of daily living (IADLs) is not well understood. This study examined measures of episodic memory, executive function, and MRI brain volumes in relation to baseline IADLs and as predictors of rate of IADL change. Participants were 124 elderly persons with cognitive function between normal and moderate dementia both with and without significant small vessel cerebrovascular disease. Random effects modeling showed that baseline memory and executive function (EXEC) were associated with baseline IADL scores, but only EXEC was independently associated with rate of change in IADLs. Whereas hippocampal and cortical gray matter volumes were significantly associated with baseline IADL scores, only hippocampal volume was associated with IADL change. In a model including cognitive and neuroimaging predictors, only EXEC independently predicted rate of decline in IADL scores. These findings indicate that greater executive dysfunction at initial assessment is associated with more rapid decline in IADLs. Perhaps executive function is particularly important with respect to maintaining IADLs. Alternatively, executive dysfunction may be a sentinel event indicating widespread cortical involvement and poor prognosis.
PMCID: PMC2877031  PMID: 17521485
Alzheimer’s disease; Vascular dementia; Memory; Everyday function; Neuroimaging; Frontal lobe
7.  The Measurement of Everyday Cognition (ECog): Scale Development and Psychometric Properties 
Neuropsychology  2008;22(4):531-544.
This article describes the development and validation of an instrument to assess cognitively mediated functional abilities in older adults, Everyday Cognition (ECog). The ECog is an informant-rated questionnaire comprised of multiple subscales. Confirmatory factor analysis (CFA) was used to examine its factor structure. Convergent validity was evaluated by comparing it to established measures of everyday function. External validity was evaluated by comparing ECog results across different clinical groups [cognitively normal, mild cognitive impairment (MCI), dementia]. CFA supported a seven-factor model including one global factor and six domain-specific factors (Everyday Memory, Language, Visuospatial Abilities, Planning, Organization, and Divided attention). The ECog correlated with established measures of functional status and global cognition, but only weakly with age and education. The clinical groups performed differently in each domain. In addition to the global factor, the Everyday Memory factor independently differentiated MCI from Normal, while the Everyday Language domain differentiated Dementia from MCI. Different subtypes of MCI also showed different patterns. Results suggest the ECog shows promise as a useful tool for the measurement of general and domain-specific everyday functions in the elderly.
PMCID: PMC2877034  PMID: 18590364
functional impairment; everyday function; aging; instrument validation; factor analysis
8.  Cognitive predictors of functional decline in vascular dementia 
This study examined changes in cognitive-functional relationships in vascular dementia (VaD) over the course of one year.
Twenty-four patients with probable VaD were administered the Dementia Rating Scale (DRS). Caregivers completed an informant-based measure of instrumental (IADL) and basic activities of daily living (BADL). Follow-up assessment was conducted one-year post-baseline.
Logistic regression revealed that changes in the DRS Initiation/Perseveration and DRS Memory subscales were significantly associated with declines in IADLs and BADLs, respectively.
Among patients with VaD, longitudinal changes in IADLs and BADLs are most strongly associated with changes in executive functioning and memory abilities, respectively. Findings suggest that different cognitive functions subserve complex instrumental and rote, habituated basic functional activities, and neuropsychological screening measures are useful in the prediction of such functional changes.
PMCID: PMC2746410  PMID: 16906630
activities of daily living (ADLs); vascular dementia (VaD); functional decline; neuropsychology; cognition; memory; executive function; Dementia Rating Scale (DRS)

Results 1-8 (8)