Synchronous neural interactions assessed by magnetoencephalography: a functional biomarker for brain disorders.

We report on a test to assess the dynamic brain function at high temporal resolution using magnetoencephalography (MEG). The essence of the test is the measurement of the dynamic synchronous neural interactions, an essential aspect of the brain function. MEG signals were recorded from 248 axial gradiometers while 142 human subjects fixated a spot of light for 45-60 s. After fitting an autoregressive integrative moving average (ARIMA) model and taking the stationary residuals, all pairwise, zero-lag, partial cross-correlations (PCC(ij)(0)) and their z-transforms (z(ij)(0)) between i and j sensors were calculated, providing estimates of the strength and sign (positive, negative) of direct synchronous coupling at 1 ms temporal resolution. We found that subsets of z(ij)(0) successfully classified individual subjects to their respective groups (multiple sclerosis, Alzheimer's disease, schizophrenia, Sjögren's syndrome, chronic alcoholism, facial pain, healthy controls) and gave excellent external cross-validation results.

Finding dementia in primary care: the results of a clinical demonstration project.

OBJECTIVES: To assess the effect of screening on diagnosing cognitive impairment. DESIGN: Quality improvement initiative. SETTING: Seven Veterans Affairs Medical Centers. PARTICIPANTS: Veterans aged 70 or older without a prior diagnosis of cognitive impairment. MEASUREMENTS: Veterans failing a brief cognitive screen (Mini-Cog score <4/5) at a routine primary care visit were offered a further, comprehensive evaluation with an advance practice registered nurse trained in dementia care and integrated into the primary care clinic. Veterans completing the evaluation were reviewed in a consensus conference and assigned a diagnosis of dementia; cognitive impairment, no dementia; or no cognitive impairment. Total numbers of screens, associated scores (0-5), and the consensus diagnoses were tallied. New cognitive impairment diagnoses were also tracked for veterans who passed the screen but requested further evaluation, failed but declined further evaluation, or were not screened. Primary care provider satisfaction with the program also was assessed. RESULTS: Of 8,342 veterans offered screening, 8,063 (97%) accepted, 2,081 (26%) failed the screen, 580 (28%) agreed to further evaluation, and 540 (93%) were diagnosed with cognitive impairment, including 432 (75%) with dementia. For screen passes requesting further evaluation, 87% (103/118) had cognitive impairment, including 70% (82/118) with dementia. Screen failures declining further evaluation had 17% (259/1,501) incident cognitive impairment diagnosed through standard care, bringing the total newly documented cognitive impairment in all screens to 11% (902/8,063), versus 4% (1,242/28,349) in similar clinics without this program. Eighty-two percent of primary care providers in clinics with this program agreed that it provided a useful service. CONCLUSION: Screening combined with offering further evaluation increased new diagnoses of cognitive impairment in older veterans two to three times. Veterans accepted screening well, and providers found the program useful.

Canonical correlation analysis of synchronous neural interactions and cognitive deficits in Alzheimer's dementia.

In previous work (Georgopoulos et al 2007 J. Neural Eng. 4 349-55) we reported on the use of magnetoencephalographic (MEG) synchronous neural interactions (SNI) as a functional biomarker in Alzheimer's dementia (AD) diagnosis. Here we report on the application of canonical correlation analysis to investigate the relations between SNI and cognitive neuropsychological (NP) domains in AD patients. First, we performed individual correlations between each SNI and each NP, which provided an initial link between SNI and specific cognitive tests. Next, we performed factor analysis on each set, followed by a canonical correlation analysis between the derived SNI and NP factors. This last analysis optimally associated the entire MEG signal with cognitive function. The results revealed that SNI as a whole were mostly associated with memory and language, and, slightly less, executive function, processing speed and visuospatial abilities, thus differentiating functions subserved by the frontoparietal and the temporal cortices. These findings provide a direct interpretation of the information carried by the SNI and set the basis for identifying specific neural disease phenotypes according to cognitive deficits.

Screening for cognitive impairment in an elderly veteran population: acceptability and results using different versions of the Mini-Cog.

OBJECTIVES: To assess the feasibility of cognitive screening in older veterans presenting for routine primary care. DESIGN: Quality improvement initiative. SETTING: Seven Veterans Affairs Medical Centers. PARTICIPANTS: Veterans aged 70 and older without a prior diagnosis of cognitive impairment. MEASUREMENTS: Scores from 16 different versions of the Mini-Cog, a 5-point cognitive screen consisting of three-word recall (0-3 points) with a clock-drawing interference task (0 or 2 points). Five word lists were paired with three clock times and randomly ordered for presentation with the original Mini-Cog version. The conventional dementia screening cut point was increased to maximize sensitivity; to pass, patients had to draw the clock correctly and recall at least two of three words (score 4 or 5/5). RESULTS: Administering the Mini-Cog took 90 to 180 seconds. Of 8,342 veterans approached, 8,063 (96.7%) agreed to be screened; 2,081 (25.8%) scored less than 4 out of 5. Scores declined with age, but age did not predict pass or fail. Different word lists produced different screen failure rates, ranging from 21.2% to 33.4%. Five dementia specialists were unable to distinguish harder from easier lists. Different clock times accounted for 2% or less of the difference in failure rates. CONCLUSION: The Mini-Cog was quick and well accepted by older veterans. Many with no prior documentation of cognitive impairment failed the screen. Failure rates varied with the word list used, revealing that even apparently minor changes in test items affect screen results. Additional study is needed to establish the value of cognitive screening in shaping primary care of older veterans.