Dana L. Penney

Prospective randomized neurocognitive and S-100 study of hypothermic circulatory arrest, retrograde brain perfusion, and antegrade brain perfusion for aortic arch operations

BACKGROUND To determine the optimal method of brain protection during deep hypothermic circulatory arrest (DHCA) for arch repair. METHODS Of 139 potential aortic arch repairs (denominator), we randomized 30 patients to either DHCA alone (n = 10), DHCA plus retrograde brain perfusion (RBP) (n = 10), or antegrade perfusion (ANTE) (n = 10); a further 5 coronary bypass (CAB) patients were controls. Fifty-one neurocognitive subscores were obtained for each patient at each of four intervals: preoperatively, 3 to 6 days postoperatively, 2 to 3 weeks postoperatively, and 6 months postoperatively. Intraoperative and postoperative S-100 blood levels and electroencephalograms were also obtained. RESULTS For the denominator, the 30-day and hospital survival rate was 97.8% (136 of 139) and the stroke rate 2.8% (4 of 139). For the randomized patients, the survival rate was 100% and no patient suffered a stroke or seizure. Circulatory arrest (CA) times were not different (DHCA: RBP:ANTE) for 11 total arch repairs (including 6 elephant trunk; mean, 41.4 minutes; standard deviation, 15). Hemiarch repairs (n = 17) were quickest with DHCA (mean 10.0 minutes; standard deviation, 3.6; p = 0.011) and longest with ANTE (mean 23.8 minutes; standard deviation, 10.28; p = 0.004). Of the patients, 96% had clinical neurocognitive impairment at 3 to 6 days, but by 2 to 3 weeks only 9% had a residual new deficit (1 DHCA, 1 RBP, 1 ANTE), and by 6 months these 3 patients had recovered. Comparison of postoperative mean scores showed the DHCA group did better than RBP patients in 5 of 7 significantly different (p < 0.05) scores and versus 9 of 9 ANTE patients. There were no S-100 level differences between CA groups, but levels were significantly higher versus the CAB controls, particularly at the end of bypass (p < 0.0001); however, these may have been influenced by other variables such as greater pump time, cardiotomy use, and postoperative autotransfusion. Circulatory arrest (p = 0.01) and pump time (p = 0.057) correlated with peak S-100 levels. CONCLUSIONS The results of hypothermic arrest have improved; however, there is no neurocognitive advantage with RBP or ANTE. Nevertheless, retrograde brain perfusion may, in a larger study, potentially reduce the risk of strokes related to embolic material. S-100 levels may be artificial. In patients with severe atheroma or high risk for embolic strokes, we use a combination of retrograde and antegrade perfusion on a selective basis.

Verbal Serial List Learning in Mild Cognitive Impairment: A Profile Analysis of Interference, Forgetting, and Errors

Using cluster analysis Libon et al. (2010) found three verbal serial list-learning profiles involving delay memory test performance in patients with mild cognitive impairment (MCI). Amnesic MCI (aMCI) patients presented with low scores on delay free recall and recognition tests; mixed MCI (mxMCI) patients scored higher on recognition compared to delay free recall tests; and dysexecutive MCI (dMCI) patients generated relatively intact scores on both delay test conditions. The aim of the current research was to further characterize memory impairment in MCI by examining forgetting/savings, interference from a competing word list, intrusion errors/perseverations, intrusion word frequency, and recognition foils in these three statistically determined MCI groups compared to normal control (NC) participants. The aMCI patients exhibited little savings, generated more highly prototypic intrusion errors, and displayed indiscriminate responding to delayed recognition foils. The mxMCI patients exhibited higher saving scores, fewer and less prototypic intrusion errors, and selectively endorsed recognition foils from the interference list. dMCI patients also selectively endorsed recognition foils from the interference list but performed similarly compared to NC participants. These data suggest the existence of distinct memory impairments in MCI and caution against the routine use of a single memory test score to operationally define MCI.

LEUKOARAIOSIS SEVERITY AND LIST-LEARNING IN DEMENTIA

In patients with dementia, leukoaraiosis (LA) was hypothesized to result in differential patterns of impairment on a verbal serial list-learning test. Using a visual rating scale, 144 dementia patients with ischemic scores <4 were re-categorized as having mild (n = 73), moderate (n = 44), or severe LA (n = 27). Mild LA was predicted to be associated with an amnestic list-learning profile, while severe LA was predicted to be associated with a dysexecutive profile. List-learning performances were standardized to a group of healthy older adults (n = 24). Analyses were conducted on a set of four factors derived from the list-learning paradigm, as well as error scores. Data indicate that LA severity is an important marker for understanding list learning in dementia.

Motor cortex stimulation in patients with Parkinson disease: 12-month follow-up in 4 patients

OBJECT Since the initial 1991 report by Tsubokawa et al., stimulation of the M1 region of cortex has been used to treat chronic pain conditions and a variety of movement disorders. METHODS A Medline search of the literature published between 1991 and the beginning of 2007 revealed 459 cases in which motor cortex stimulation (MCS) was used. Of these, 72 were related to a movement disorder. More recently, up to 16 patients specifically with Parkinson disease were treated with MCS, and a variety of results were reported. In this report the authors describe 4 patients who were treated with extradural MCS. RESULTS Although there were benefits seen within the first 6 months in Unified Parkinsons Disease Rating Scale Part III scores (decreased by 60%), tremor was only modestly managed with MCS in this group, and most benefits seen initially were lost by the end of 12 months. CONCLUSIONS Although there have been some positive findings using MCS for Parkinson disease, a larger study may be needed to better determine if it should be pursued as an alternative surgical treatment to DBS.

Clock drawing in the Montreal Cognitive Assessment: recommendations for dementia assessment.

Background: Clock drawing is part of the Montreal Cognitive Assessment (MoCA) test but may have administration and scoring limitations. We assessed (1) the reliability of the MoCA clock criteria relative to a published error scoring approach, (2) whether command-only administration could distinguish dementia from cognitively intact individuals and (3) the value of adding a clock copy condition to the MoCA. Methods: Three novice raters and clocks from dementia and control participants were used to assess the 3 aims. Results: MoCA interrater and intrarater reliability were low (i.e. intraclass correlation coefficient = 0.12–0.31) and required repeat training. Clocks drawn to command classified dementia at chance. Inclusion of a copy condition demonstrated expected dementia subgroup patterns. Conclusion: Reliable clock scoring with MoCA criteria requires practice. Supplementing a clock copy to the standard MoCA test (takes <1 min) will improve dementia assessment.

Dysexecutive Functioning in Mild Cognitive Impairment: Derailment in Temporal Gradients

Libon et al. (2010) provided evidence for three statistically determined clusters of patients with mild cognitive impairment (MCI): amnesic (aMCI), dysexecutive (dMCI), and mixed (mxMCI). The current study further examined dysexecutive impairment in MCI using the framework of Fusters (1997) derailed temporal gradients, that is, declining performance on executive tests over time or test epoch. Temporal gradients were operationally defined by calculating the slope of aggregate letter fluency output across 15-s epochs and accuracy indices for initial, middle, and latter triads from the Wechsler Memory Scale-Mental Control subtest (Boston Revision). For letter fluency, slope was steeper for dMCI compared to aMCI and NC groups. Between-group Mental Control analyses for triad 1 revealed worse dMCI performance than NC participants. On triad 2, dMCI scored lower than aMCI and NCs; on triad 3, mxMCI performed worse versus NCs. Within-group Mental Control analyses yielded equal performance across all triads for aMCI and NC participants. mxMCI scored lower on triad 1 compared to triads 2 and 3. dMCI participants also performed worse on triad 1 compared to triads 2 and 3, but scored higher on triad 3 versus triad 2. These data suggest impaired temporal gradients may provide a useful heuristic for understanding dysexecutive impairment in MCI.

THink: Inferring Cognitive Status from Subtle Behaviors

The Digital Clock Drawing Test is a fielded application that provides a major advance over existing neuropsychological testing technology. It captures and analyzes high precision information about both outcome and process, opening up the possibility of detecting subtle cognitive impairment even when test results appear superficially normal. We describe the design and development of the test, document the role of AI in its capabilities, and report on its use over the past seven years. We outline its potential implications for earlier detection and treatment of neurological disorders. We also set the work in the larger context of the THink project, which is exploring multiple approaches to determining cognitive status through the detection and analysis of subtle behaviors.

Digital Clock Drawing: differentiating "thinking" versus "doing" in younger and older adults with depression.

Psychomotor slowing has been documented in depression. The digital Clock Drawing Test (dCDT) provides: (i) a novel technique to assess both cognitive and motor aspects of psychomotor speed within the same task and (ii) the potential to uncover subtleties of behavior not previously detected with non-digitized modes of data collection. Using digitized pen technology in 106 participants grouped by Age (younger/older) and Affect (euthymic/unmedicated depressed), we recorded cognitive and motor output by capturing how the clock is drawn rather than focusing on the final product. We divided time to completion (TTC) for Command and Copy conditions of the dCDT into metrics of percent of drawing (%Ink) versus non-drawing (%Think) time. We also obtained composite Z-scores of cognition, including attention/information processing (AIP), to explore associations of %Ink and %Think times to cognitive and motor performance. Despite equivalent TTC, %Ink and %Think Command times (Copy n.s.) were significant (AgeXAffect interaction: p=.03)-younger depressed spent a smaller proportion of time drawing relative to thinking compared to the older depressed group. Command %Think time negatively correlated with AIP in the older depressed group (r=-.46; p=.02). Copy %Think time negatively correlated with AIP in the younger depressed (r=-.47; p=.03) and older euthymic groups (r=-.51; p=.01). The dCDT differentiated aspects of psychomotor slowing in depression regardless of age, while dCDT/cognitive associates for younger adults with depression mimicked patterns of older euthymics.

DIGITIZED CLOCK DRAWING (DCTCLOCKTM) PERFORMANCE AND ITS RELATIONSHIP TO AMYLOID AND TAU PET IMAGING MARKERS IN UNIMPAIRED OLDER ADULTS

Department of Molecular Neuroscience and Reta Lila Research Laboratories, University College London Institute of Neurology, London, United Kingdom; Centre for Medical Image Computing, Department of Computer Science, University College London, London, United Kingdom; Department of Computer Science and Centre for Medical Image Computing, University College London, London, United Kingdom. Contact e-mail: a.strydom@ucl.ac.uk

DETECTING SUBTLE COGNITIVE IMPAIRMENT WITH THE DIGITAL MAZE COMPLETION TEST

performance in the smooth pursuit task. This model validation allows descriptions of individual patients’ data, as compared to a healthy control, to be made with confidence. Identifying areas of their sequences that either conform to or deviate from a healthy performance can provide valuable insight into an individual’s basic oculo-motor function. Subject to further validation from more data, the classification procedure could form the basis of a noninvasive automatic diagnostic tool for dementia.