Diffusion tensor imaging parameters in mild traumatic brain injury and its correlation with early neuropsychological impairment: a longitudinal study

We explored the prognostic value of diffusion tensor imaging (DTI) parameters of selected white matter (WM) tracts in predicting neuropsychological outcome, both at baseline and 6 months later, among well-characterized patients diagnosed with mild traumatic brain injury (mTBI). Sixty-one patients with mTBI (mean age=27.08; standard deviation [SD], 8.55) underwent scanning at an average of 10 h (SD, 4.26) post-trauma along with assessment of their neuropsychological performance at an average of 4.35 h (SD, 7.08) upon full Glasgow Coma Scale recovery. Results were then compared to 19 healthy control participants (mean age=29.05; SD, 5.84), both in the acute stage and 6 months post-trauma. DTI and neuropsychological measures between acute and chronic phases were compared, and significant differences emerged. Specifically, chronic-phase fractional anisotropy and radial diffusivity values showed significant group differences in the corona radiata, anterior limb of internal capsule, cingulum, superior longitudinal fasciculus, optic radiation, and genu of corpus callosum. Findings also demonstrated associations between DTI indices and neuropsychological outcome across two time points. Our results provide new evidence for the use of DTI as an imaging biomarker and indicator of WM damage occurring in the context of mTBI, and they underscore the dynamic nature of brain injury and possible biological basis of chronic neurocognitive alterations

Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients.

In December 2017, the National Academy of Neuropsychology convened an interorganizational Summit on Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients in Denver, Colorado. The Summit brought together representatives of a broad range of stakeholders invested in the care of older adults to focus on the topic of cognitive health and aging. Summit participants specifically examined questions of who should be screened for cognitive impairment and how they should be screened in medical settings. This is important in the context of an acute illness given that the presence of cognitive impairment can have significant implications for care and for the management of concomitant diseases as well as pose a major risk factor for dementia. Participants arrived at general principles to guide future screening approaches in medical populations and identified knowledge gaps to direct future research. Key learning points of the summit included: recognizing the importance of educating patients and healthcare providers about the value of assessing current and baseline cognition;emphasizing that any screening tool must be appropriately normalized and validated in the population in which it is used to obtain accurate information, including considerations of language, cultural factors, and education; andrecognizing the great potential, with appropriate caveats, of electronic health records to augment cognitive screening and tracking of changes in cognitive health over time

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies

Missense mutation of Brain Derived Neurotrophic Factor (BDNF) alters neurocognitive performance in patients with mild traumatic brain injury: a longitudinal study

The predictability of neurocognitive outcomes in patients with traumatic brain injury is not straightforward. The extent and nature of recovery in patients with mild traumatic brain injury (mTBI) are usually heterogeneous and not substantially explained by the commonly known demographic and injury-related prognostic factors despite having sustained similar injuries or injury severity. Hence, this study evaluated the effects and association of the Brain Derived Neurotrophic Factor (BDNF) missense mutations in relation to neurocognitive performance among patients with mTBI. 48 patients with mTBI were prospectively recruited and MRI scans of the brain were performed within an average 10.1 (SD 4.2) hours post trauma with assessment of their neuropsychological performance post full Glasgow Coma Scale (GCS) recovery. Neurocognitive assessments were repeated again at 6 months follow-up. The paired t-test, Cohen’s d effect size and repeated measure ANOVA were performed to delineate statistically significant differences between the groups [wildtype G allele (Val homozygotes) vs. minor A allele (Met carriers)] and their neuropsychological performance across the time point (T1 = baseline/ admission vs. T2 = 6th month follow-up). Minor A allele carriers in this study generally performed more poorly on neuropsychological testing in comparison wildtype G allele group at both time points. Significant mean differences were observed among the wildtype group in the domains of memory (M = -11.44, SD = 10.0, p = .01, d = 1.22), executive function (M = -11.56, SD = 11.7, p = .02, d = 1.05) and overall performance (M = -6.89 SD = 5.3, p = .00, d = 1.39), while the minor A allele carriers showed significant mean differences in the domains of attention (M = -11.0, SD = 13.1, p = .00, d = .86) and overall cognitive performance (M = -5.25, SD = 8.1, p = .01, d = .66).The minor A allele carriers in comparison to the wildtype G allele group, showed considerably lower scores at admission and remained impaired in most domains across the timepoints, although delayed signs of recovery were noted to be significant in the domains attention and overall cognition. In conclusion, the current study has demonstrated the role of the BDNF rs6265 Val66Met polymorphism in influencing specific neurocognitive outcomes in patients with mTBI. Findings were more detrimentally profound among Met allele carriers

Neurobehavioral functioning in Parkinson's disease: The role of basal ganglia-thalamocortical circuit loops in predicting performance.

Motivated by current neuroanatomic theories of basal ganglia-thalamocortical circuit loops, this study assessed whether disturbed neuronal outflow from the striatum (occurring in Parkinson's Disease) would lead to circumscribed deficits in cognitive functions thought to be dependent upon the functional integrity of the frontal lobes, the cortical destination of efferent striatal neurons (particularly arising from the caudate nucleus). Further, this study investigated whether such deficits could account for previously reported memory and visuoperceptual difficulties observed in Parkinson's disease (PD) patients. Nineteen nondemented PD patients were matched with 19 normal elderly control subjects on the basis of age, gender, education, and estimated premorbid intelligence. Determination of disease onset and course, severity of motor symptoms, and medication regimen were made on all PD patients. Three categories of neuropsychologic tests were given: (1) tests sensitive to prefrontal cortical dysfunction (the California Sorting Test, a modified version of the Wisconsin Card Sorting Test, temporal ordering, and generative naming), (2) implicit and explicit memory tests (a fragmented pictures test, serial reaction time, continuous recognition memory, and word learning), and (3) visuomotor and perceptual characteristics (including the Block Design and Picture Arrangement subtests of the WAIS-R, Benton Facial Recognition Test, Benton Right-Left Discrimination, and Benton Visual Form Discrimination Test). Consistent with the functional/anatomic hypothesis of subcortical deafferentation of the frontal lobes, the nondemented PD patients demonstrated selective deficits in cognitive functions thought to be dependent upon the functional integrity of the prefrontal cortex; other tasks presumed to rely on other cortical regions and processes (e.g., learning and memory, visuoperceptual and visuoconstructional skills) were not significantly impaired--once performance on the frontally-related tasks was statistically covaried. Results are discussed in terms of the validity of the outflow model in predicting the performance of nondemented PD patients on neuropsychologic measures

Implicit and explicit memory in Alzheimer's disease and Parkinson's disease

Several tasks examined implicit and explicit memory in matched samples of Alzheimer's (AD) and Parkinson's disease (PD) patients, and healthy elderly subjects. Lexical priming, pursuit-rotor tracking, and a fragmented pictures test, followed by explicit memory tests, were given. AD patients were impaired on all explicit tests and on lexical priming, but were intact on pursuit-rotor tracking and the procedural learning (PL) component of the fragmented pictures test. PD patients were significantly better than AD patients on all explicit memory tests, but were selectively impaired on the PL component of the fragmented pictures test. Finally, a mirror reading test was given to the PD patients and matched control subjects, with no significant differences in performance between the two groups demonstrated. Results are discussed in terms of hypothetical cognitive processes and brain circuits underlying different explicit and implicit memory domains

Diffusion Tensor Imaging Parameters in Mild Traumatic Brain Injury and Its Correlation with Early Neuropsychological Impairment: A Longitudinal Study.

We explored the prognostic value of diffusion tensor imaging (DTI) parameters of selected white matter (WM) tracts in predicting neuropsychological outcome, both at baseline and 6 months later, among well-characterized patients diagnosed with mild traumatic brain injury (mTBI). Sixty-one patients with mTBI (mean age=27.08; standard deviation [SD], 8.55) underwent scanning at an average of 10 h (SD, 4.26) post-trauma along with assessment of their neuropsychological performance at an average of 4.35 h (SD, 7.08) upon full Glasgow Coma Scale recovery. Results were then compared to 19 healthy control participants (mean age=29.05; SD, 5.84), both in the acute stage and 6 months post-trauma. DTI and neuropsychological measures between acute and chronic phases were compared, and significant differences emerged. Specifically, chronic-phase fractional anisotropy and radial diffusivity values showed significant group differences in the corona radiata, anterior limb of internal capsule, cingulum, superior longitudinal fasciculus, optic radiation, and genu of corpus callosum. Findings also demonstrated associations between DTI indices and neuropsychological outcome across two time points. Our results provide new evidence for the use of DTI as an imaging biomarker and indicator of WM damage occurring in the context of mTBI, and they underscore the dynamic nature of brain injury and possible biological basis of chronic neurocognitive alterations

Pupillary Responses as a Biomarker of Early Risk for Alzheimer’s Disease

Task-evoked pupillary responses may be a psychophysiological biomarker of early risk for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Pupil dilation during cognitive tasks reflects cognitive effort until compensatory capacity is surpassed and performance declines are manifest, and reflects activation in the locus coeruleus, where degenerative changes have been found in the earliest stages of AD. We recorded pupillary responses during digit span recall in 918 participants ages 56-66. Despite normal performance, amnestic single-domain MCI (S-MCI) participants showed greater pupil dilation than non-amnestic S-MCI and cognitively normal (CN) participants at lower cognitive loads. Multi-domain MCI (M-MCI) participants failed to modulate effort across cognitive loads and showed poorer performance. Pupillary responses differentiated MCI and CN groups. Amnestic S-MCI participants required compensatory effort to maintain performance, consistent with increased risk for decline. Greater effort in CN individuals might indicate risk for MCI. Results are consistent with dysfunction in locus coeruleus-linked brain systems. This brief task shows promise as a biomarker for early MCI and AD risk prediction