Case study: A positive cognitive outcome following an out-of-hospital cardiac arrest.

OBJECTIVE: Time is critical with any out of hospital cardiac arrest (OHCA). The possibility of brain cell death increases, and the likelihood of a "good" outcome decreases with time. The most prominent impairments involve memory and attentional difficulties. Limited research and few cases have shown positive cognitive results following an OHCA to the extent that this case study depicts. METHOD: The current case study presents a right-handed male in his late 40s, with master's and law degrees, and a high-level functioning in the workplace who experienced an OHCA. He was treated for his OHCA and subsequently underwent neuropsychological testing less than 2 months following his hospital discharge. RESULTS: Expected results suggest impairments in key cognitive areas; however, a neuropsychological exam less than 2-months post-incident, testing pre-morbid IQ, overall cognitive ability, processing speed, attention, executive functioning, language, visuospatial abilities, and memory; each showing normal or better results. Additionally, self and collateral report questionnaires examining cognitive and emotional functioning reported no difficulties and no major changes since his cardiac arrest. CONCLUSIONS: We speculate that this patient's exceptional outcome might be due to his cognitive reserve, and the immediateness of his intervention (5-10 min of CPR and return-of-spontaneous-circulation from an AED shock) and use of a saline cooling procedure upon arrival to the hospital. Overall, we highlight a patient with a remarkable cognitive outcome, utilizing data from neuropsychological testing within 2-months post-incident, and propose protective factors in neuropsychological functioning following an OHCA.

Low-frequency stimulation of a fiber tract in bilateral temporal lobe epilepsy.

OBJECTIVE: Pharmacoresistant bilateral mesial temporal lobe epilepsy often implies poor resective surgical candidacy. Low-frequency stimulation of a fiber tract connected to bilateral hippocampi, the fornicodorsocommissural tract, has been shown to be safe and efficacious in reducing seizures in a previous short-term study. Here, we report a single-blinded, within-subject control, long-term deep-brain stimulation trial of low-frequency stimulation of the fornicodorsocommissural tract in bilateral mesial temporal lobe epilepsy. Outcomes of interest included safety with respect to verbal memory scores and reduction of seizure frequency. METHODS: Our enrollment goal was 16 adult subjects to be randomized to 2-Hz or 5-Hz low-frequency stimulation of the fornicodorsocommissural tract starting at 2 mA. The study design consisted of four two-month blocks of stimulation with a 50%-duty cycle, alternating with two-month blocks of no stimulation. RESULTS: We terminated the study after enrollment of five subjects due to slow accrual. Fornicodorsocommissural tract stimulation elicited bilateral hippocampal evoked responses in all subjects. Three subjects underwent implantation of pulse generators and long-term low-frequency stimulation with mean monthly seizures of 3.14 ±â€¯2.67 (median 3.0 [IQR 1-4.0]) during stimulation-off blocks, compared with 0.96 ±â€¯1.23 (median 1.0 [IQR 0-1.0]) during stimulation-on blocks (p = 0.0005) during the blinded phase. Generalized Estimating Equations showed that low-frequency stimulation reduced monthly seizure-frequency by 0.71 per mA (p < 0.001). Verbal memory scores were stable with no psychiatric complications or other adverse events. SIGNIFICANCE: The results demonstrate feasibility of stimulating both hippocampi using a single deep-brain stimulation electrode in the fornicodorsocommissural tract, efficacy of low-frequency stimulation in reducing seizures, and safety as regards verbal memory.

Prevalence and correlates of concussion in children: Data from the Adolescent Brain Cognitive Development study.

INTRODUCTION: Concussions are one of the most common causes for emergency room use in the United States (US) among youth and adolescents; however, prevalence data on concussion in this population are inconsistent. A growing body of literature has explored associations of a range of variables with pediatric concussion, but they have not been explored simultaneously in a well-powered sample in the US. The present study aimed to present lifetime concussion prevalence, evaluate demographic, psychological, and cognitive correlates of concussion, and assess for differences across these variables based on age of first concussion in a large sample of US children. METHODS: We analyzed the Adolescent Brain Cognitive Development (ABCD) sample, which monitors biopsychosocial development in 11,875 children at 21 sites across the US between ages 9 and 10. Along with presenting rates of concussion, we also evaluated the association of demographics, sleep disturbance, cognitive functioning, and externalizing and internalizing symptoms with concussion history using backwards binary logistic regression. We further conducted univariate comparisons of all variables between those who experienced their first concussion before and after age 5. Significance was based on α = .02, with Benjamini-Hochberg FDR adjustments for multiple comparisons. RESULTS: We found approximately 4% of the sample had experienced a concussion, and significant correlates of experiencing a concussion were male sex, increased family income, and higher somatic symptoms after FDR correction. Symptoms of ADHD were also noted as nominally significant. No differences based on age of first concussion were found. DISCUSSION: Our analyses provided updated prevalence estimates of pediatric concussion in the US that aligns with many hospital records-based studies. Our findings largely mirrored those in the literature with the exception of somatic symptoms. Limitations of findings and implications of individual findings are discussed.

The effects of lutein and zeaxanthin on resting state functional connectivity in older Caucasian adults: a randomized controlled trial.

The carotenoids lutein (L) and zeaxanthin (Z) accumulate in retinal regions of the eye and have long been shown to benefit visual health. A growing literature suggests cognitive benefits as well, particularly in older adults. The present randomized controlled trial sought to investigate the effects of L and Z on brain function using resting state functional magnetic resonance imaging (fMRI). It was hypothesized that L and Z supplementation would (1) improve intra-network integrity of default mode network (DMN) and (2) reduce inter-network connectivity between DMN and other resting state networks. 48 community-dwelling older adults (mean age = 72 years) were randomly assigned to receive a daily L (10 mg) and Z (2 mg) supplement or a placebo for 1 year. Resting state fMRI data were acquired at baseline and post-intervention. A dictionary learning and sparse coding computational framework, based on machine learning principles, was used to investigate intervention-related changes in functional connectivity. DMN integrity was evaluated by calculating spatial overlap rate with a well-established DMN template provided in the neuroscience literature. Inter-network connectivity was evaluated via time series correlations between DMN and nine other resting state networks. Contrary to expectation, results indicated that L and Z significantly increased rather than decreased inter-network connectivity (Cohen's d = 0.89). A significant intra-network effect on DMN integrity was not observed. Rather than restoring what has been described in the available literature as a "youth-like" pattern of intrinsic brain activity, L and Z may facilitate the aging brain's capacity for compensation by enhancing integration between networks that tend to be functionally segregated earlier in the lifespan.

Intelligence moderates the relationship between age and inter-connectivity of resting state networks in older adults.

Age-related changes in the interactive behavior of default mode network (DMN) with other resting state networks are poorly understood. We hypothesized that age would positively correlate with inter-network connectivity in late life and intellectual functioning was expected to moderate this relationship. The sample consisted of 48 community-dwelling older adults with resting state functional magnetic resonance imaging data. Global inter-connectivity between DMN and 9 other resting state networks was calculated using a novel computational framework based on machine learning. Intellectual functioning (intelligence) was estimated using the Wechsler Test of Adult Reading. A significant, positive relationship was found between age and global inter-network connectivity (r = 0.31, p = 0.029). Moderation analyses yielded a significant age × intelligence interaction term (p = 0.003), such that intelligence attenuated the relationship between age and global inter-network connectivity. Taken together, these results suggest that age is positively associated with global DMN desegregation, possibly due to dedifferentiation or compensation. Intellectual functioning moderates this relationship, such that more intelligent older adults maintain a segregated DMN profile.

Lutein and Zeaxanthin Influence Brain Function in Older Adults: A Randomized Controlled Trial.

OBJECTIVES: The present study constitutes the first randomized controlled trial to investigate the relation of lutein (L) and zeaxanthin (Z) to brain function using functional magnetic resonance imaging (fMRI). It was hypothesized that L and Z supplementation in older adults would enhance neural efficiency (i.e., reduce activation) and cognitive performance on a verbal learning task relative to placebo. METHODS: A total of 44 community-dwelling older adults (mean age=72 years) were randomly assigned to receive either placebo or L+Z supplementation (12 mg/daily) for 1 year. Neurocognitive performance was assessed at baseline and post-intervention on an fMRI-adapted task involving learning and recalling word pairs. Imaging contrasts of blood-oxygen-level-dependent (BOLD) signal were created by subtracting active control trials from learning and recall trials. A flexible factorial model was employed to investigate the expected group (placebo vs. supplement) by time (baseline vs. post-intervention) interaction in pre-specified regions-of-interest. RESULTS: L and Z appeared to buffer cognitive decline on the verbal learning task (Cohen's d=.84). Significant interactions during learning were observed in left dorsolateral prefrontal cortex and anterior cingulate cortex (p < .05, family-wise-error corrected). However, these effects were in the direction of increased rather than decreased BOLD signal. Although the omnibus interaction was not significant during recall, within-group contrasts revealed significant increases in left prefrontal activation in the supplement group only. CONCLUSIONS: L and Z supplementation appears to benefit neurocognitive function by enhancing cerebral perfusion, even if consumed for a discrete period of time in late life. (JINS, 2018, 24, 77-90).

Discounting preferences and response consistency as markers of functional ability in community-dwelling older adults.

INTRODUCTION: Predictors of functional independence in older adults are in need. Based on findings that delay discounting, probability discounting, and the ability to respond consistently use cognitive abilities and neural systems with central relevance to functional ability, the present study evaluated whether these behavioral economic variables account for variance in everyday functioning in older adults. It was hypothesized that greater preference for immediate/probabilistic rewards and response inconsistency would independently predict decrements in instrumental activities of daily living (IADLs). METHOD: Participants included 64 community-dwelling older adults (65-85 years; mean age = 76.25 years; 76.60% female). Exclusionary criteria were neurological illness, illiteracy, substance dependence within the past 5 years, score of ≤20 on the Mini-Mental State Examination, and/or presence of dementia. Delay/probability discounting tasks consisted of a series of dichotomous selections between smaller, immediate/guaranteed and larger, delayed/probabilistic monetary values. Area under the curve (AUC) was used to index levels of discounting, while response (in)consistency was based on the percentage of contradictory responses. The Direct Assessment of Functional Status-Revised (DAFS-R) provided a performance-based assessment of IADLs. Hierarchical regression analyses were conducted to determine whether discounting preferences and response consistency accounted for variance in functional ability over and above relevant demographic characteristics. RESULTS: Demographic characteristics accounted for significance variance in IADLs (p = .001, R(2) = .237). Probability discounting AUC (p = .014, ΔR(2) = .075) and response (in)consistency (p = .046, ΔR(2) = .050) each accounted for significant additional variance in functional ability, as did delay discounting response (in)consistency (p = .010, ΔR(2) = .081). Delay discounting AUC did not add significantly to the model (p = .861). CONCLUSIONS: Discounting preferences and choice consistency hold potential to serve as relatively fast and inexpensive markers of functional decline, likely due to neurocognitive deterioration relevant to both behavioral economic decision making and functional independence.

Delay and probability discounting as candidate markers for dementia: an initial investigation.

The present study investigated delay discounting and probability discounting-behavioral economic indices of impulsivity and risk proneness, respectively-in 39 healthy older adults and 25 older adults with mild cognitive impairment (MCI). Relative to the healthy group, it was hypothesized that older adults with MCI would display greater levels of impulsivity, risk proneness, and response inconsistency. The MCI group was found to display a unique delay discounting profile characterized by increasing impulsivity with decreasing reward magnitude, such that cognitively impaired older adults were significantly more impulsive than healthy controls at the small reward magnitude. The two groups exhibited similar levels of probability discounting, though older adults with MCI were significantly less consistent in their risk preferences. The present findings shed light onto decision-making in pre-dementia disease stages and suggest that discounting performance holds potential to complement early diagnostic instruments, likely due to pathophysiological processes in relevant brain regions.

Cognitive reserve moderates relation between global cognition and functional status in older adults.

The ability to perform instrumental activities of daily living (IADLs) is necessary for independent living. Research suggests that community-dwelling older adults are at risk for experiencing subtle decrements in the performance of IADLs. Neuropsychological tests have been used to account for differences in IADL status. Studies of the relationship between cognitive ability and functional status have produced variable results, however, and cognitive ability appears to be only a moderate predictor. Several studies of normal aging have revealed cognitive and functional benefits of higher cognitive reserve (CR) in healthy, nondemented older adults. The purposes of the present study were to: (a) examine the relationship between global cognitive ability and IADL performance among 53 community-dwelling older adults, and (b) determine whether formal education, as a proxy of CR, significantly moderates this relationship. Consistent with previous findings, global cognitive ability accounted for a considerable portion of variance in IADL performance [ΔR(2) = .54; ΔF(2, 53) = 67.96; p < .001]. Additionally, CR modestly but significantly attenuated this relationship [ΔR(2) = .044; ΔF(4, 53) = 5.98; p = .018; total R(2) = .65]. This finding suggests that community-dwelling older adults with lower levels of formal education may be at greater risk for functional decrements associated with age-related cognitive decline.

Lateral temporal hyper-activation as a novel biomarker of mild cognitive impairment.

Memory dysfunction in mild cognitive impairment (MCI) due to Alzheimer's pathology is primarily associated with episodic memory deficits linked to deterioration of the medial temporal lobes (MTLs). Currently, there is a call to discover novel biomarkers of MCI in order to improve research criteria. Functional activation differences in MCI during episodic memory-task performance are often evidenced in the MTLs, and frontal and parietal lobes, but it has been suggested that examination of working memory (WM) differences may be more useful in detecting MCI. In the current study, MCI and control participants performed a complex WM span (CWMS) task while functional magnetic resonance imaging (fMRI) data were acquired. Results indicated hyper-activation of the lateral temporal lobes, MTLs, and frontal and parietal regions during encoding and maintenance, and hyper-activation of the lateral temporal, frontal, and parietal lobes during CWMS recall for the MCI participants. Medial and lateral temporal differences during encoding and maintenance are consistent with previous findings, but lateral temporal differences are often not elaborated upon. Hyper-activation of the lateral temporal lobes during WM encoding and maintenance, and also during recall, suggests that this region may provide valuable information regarding WM impairment in MCI and Alzheimer's. Given that whole-brain functional imaging of the MTLs is often limited due to artifact and partial voluming of sub-fields, examination of lateral temporal differences may provide a novel biomarker related to WM impairment in MCI.

Openness to experience is related to better memory ability in older adults with questionable dementia.

The personality traits Openness to experience and Neuroticism of the five-factor model have previously been associated with memory performance in nondemented older adults, but this relationship has not been investigated in samples with memory impairment. Our examination of 50 community-dwelling older adults (29 cognitively intact; 21 with questionable dementia as determined by the Clinical Dementia Rating Scale) showed that demographic variables (age, years of education, gender, and estimated premorbid IQ) and current depressive symptoms explained a significant amount of variance of Repeatable Battery of Neuropsychological Status Delayed Memory (adjusted R (2) = 0.23). After controlling for these variables, a measure of global cognitive status further explained a significant portion of variance in memory performance (ΔR(2) = 0.13; adjusted R(2) = 0.36; p < .01). Finally, adding Openness to this hierarchical linear regression model explained a significant additional portion of variance (ΔR(2) = 0.08; adjusted R(2) = 0.44; p < .01) but adding Neuroticism did not explain any additional variance. This significant relationship between Openness and better memory performance above and beyond one's cognitive status and demographic variables may suggest that a lifelong pattern of involvement in new cognitive activities could be preserved in old age or protect from memory decline. This study suggests that personality may be a powerful predictor of memory ability and clinically useful in this heterogeneous population.

Lack of long-term fMRI differences after multiple sports-related concussions.

INTRODUCTION: Mild traumatic brain injury (mTBI) or concussion has been acutely associated with several cognitive symptoms, including deficits in response inhibition, working memory and motor performance. The pervasiveness of these cognitive symptoms has been more controversial. The effects of multiple concussions on neuropsychological functioning and brain activation following at least 6-months post-mTBI were examined. METHODS: Twenty right-handed male athletes with a history of at least two concussions and 20 age/pre-morbid IQ/athletic-experience matched controls underwent neuropsychological assessment and fMRI scanning where they performed versions of a colour-word Stroop interference task, an operation-span working memory task and a finger-tapping task. RESULTS: The Attention index score on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was lower for the concussion group, but only at liberal statistical threshold. Total RBANS score approached statistical significance. Reaction time during neurobehavioural tasks was similar across groups, but accuracy was reduced in the concussed group on the working memory task. Despite expected activation patterns within each group, there were no group differences in neural activation on any functional tasks using either whole-brain or ROI-specific analyses at liberal statistical thresholds. CONCLUSION: There were minimal differences between the two closely matched groups. Results point to the relative plasticity of younger adults' cognitive abilities following concussion.