Objectives: Cognitive dysfunction from high altitude exposure is a major cause of civilian and military air disasters. Pilot training improves recognition of the early symptoms of altitude exposure so that countermeasures may be taken before loss of consciousness. Little is known regarding the nature of cognitive impairments manifesting within this critical window when life-saving measures may still be taken. Prior studies evaluating cognition during high altitude simulation have predominantly focused on measures of reaction time and other basic attention or motor processes. Memory encoding, retention, and retrieval represent critical cognitive functions that may be vulnerable to acute hypoxic/ischemic events and could play a major role in survival of air emergencies, yet these processes have not been studied in the context of high altitude simulation training. Methods: In a series of experiments, military aircrew underwent neuropsychological testing before, during, and after brief (15 min) exposure to high altitude simulation (20,000 ft) in a pressure-controlled chamber. Results: Acute exposure to high altitude simulation caused rapid impairment in learning and memory with relative preservation of basic visual and auditory attention. Memory dysfunction was predominantly characterized by deficiencies in memory encoding, as memory for information learned during high altitude exposure did not improve after washout at sea level. Retrieval and retention of memories learned shortly before altitude exposure were also impaired, suggesting further impairment in memory retention. Conclusions: Deficits in memory encoding and retention are rapidly induced upon exposure to high altitude, an effect that could impact life-saving situational awareness and response. (JINS, 2017, 23, 1–10)

Objectives: It is well known that the carotenoids lutein (L) and zeaxanthin (Z) improve eye health and an accumulating evidence base suggests cognitive benefits as well. The present study investigated underlying neural mechanisms using functional magnetic resonance imaging (fMRI). It was hypothesized that lower L and Z concentrations would be associated with neurobiological inefficiency (i.e., increased activation) during cognitive performance. Methods: Forty-three community-dwelling older adults (mean age=72 years; 58% female; 100% Caucasian) were asked to learn and recall pairs of unrelated words in an fMRI-adapted paradigm. L and Z levels were measured in retina (macular pigment optical density) and serum using validated procedures. Results: Following first-level contrasts of encoding and retrieval trials minus control trials (p<.05, family-wise error corrected, minimum voxel cluster=8), L and Z were found to significantly and negatively relate to blood-oxygen-level-dependent signal in central and parietal operculum cortex, inferior frontal gyrus, supramarginal gyrus, planum polare, frontal and middle temporal gyrus, superior parietal lobule, postcentral gyrus, precentral gyrus, occipital cortex bilaterally, and cerebellar regions. Conclusions: To the authors’ knowledge, the present study represents the first attempt to investigate neural mechanisms underlying the relation of L and Z to cognition using fMRI. The observed results suggest that L and Z promote cognitive functioning in old age by enhancing neural efficiency. (JINS, 2017, 23, 11–22)

Objectives: Previous studies have found that oxytocin (OXT) can improve the recognition of emotional facial expressions; it has been proposed that this effect is mediated by an increase in attention to the eye-region of faces. Nevertheless, evidence in support of this claim is inconsistent, and few studies have directly tested the effect of oxytocin on emotion recognition via altered eye-gaze Methods: In a double-blind, within-subjects, randomized control experiment, 40 healthy male participants received 24 IU intranasal OXT and placebo in two identical experimental sessions separated by a 2-week interval. Visual attention to the eye-region was assessed on both occasions while participants completed a static facial emotion recognition task using medium intensity facial expressions. Results: Although OXT had no effect on emotion recognition accuracy, recognition performance was improved because face processing was faster across emotions under the influence of OXT. This effect was marginally significant (p<.06). Consistent with a previous study using dynamic stimuli, OXT had no effect on eye-gaze patterns when viewing static emotional faces and this was not related to recognition accuracy or face processing time. Conclusions: These findings suggest that OXT-induced enhanced facial emotion recognition is not necessarily mediated by an increase in attention to the eye-region of faces, as previously assumed. We discuss several methodological issues which may explain discrepant findings and suggest the effect of OXT on visual attention may differ depending on task requirements. (JINS, 2017, 23, 23–33)

Objectives: With comparable baseline performance on executive functions (EF) and memory between Alzheimer’s disease (AD) and behavioral-variant frontotemporal dementia (bvFTD), it is currently unclear if both diseases can be distinguished longitudinally on these measures reliably. Methods: A total of 111 participants (33 AD, 31 bvFTD, and 47 controls) were followed-up annually over a 4-year period and tested on measures of EF, memory, and orientation. Linear mixed-effect models were constructed using disease severity as a nuisance variable to examine profiles of neuropsychological performance decline. Results: At baseline, overlap in terms of cognitive impairment between bvFTD and AD on multiple EF, memory, and orientation measures was present. Longitudinally, only disinhibition (Hayling total errors) appeared sensitive to discriminating AD from bvFTD; however, only after the first annual follow-up. Subgroup analyses on smaller samples revealed comparable profiles on EF tasks at baseline and over time between bvFTD and AD who presented with impaired EF at presentation, and on memory and orientation tasks between AD and bvFTD who presented with severe amnesia. Conclusions: Our results replicate previous findings showing only moderate discriminability between AD and bvFTD at clinical presentation on EF and memory measures. More importantly, we also show that longitudinal trajectories strongly overlap for both dementias on these measures. Disinhibition emerged as the sole measure that in the long run was significantly more impaired in bvFTD. Future studies should use tests designed to target cortical regions that are specifically impaired in bvFTD, such as the ventromedial prefrontal cortex, to improve the accurate discrimination of these diseases. (JINS, 2017, 23, 34–43)

Objectives: Mild cognitive impairments (MCI) is a transitional state in aging associated with increased risk of incident dementia. The current study investigated whether MCI status moderated the effect of time on word generation during verbal fluency tasks. Specifically, the objective was to determine whether MCI status had differential effects on initial automatic or latter more effortful retrieval processes of fluency tasks. Methods: Participants were community residing older adults enrolled in a longitudinal cohort study. Of the 408 participants, 353 were normal (age=76.06±6.61; %female=57.8) and 55 were diagnosed with MCI (age=78.62±7.00; %female=52.7). Phonemic and category fluency were each administered for 60 s, but performance was recorded at three consecutive 20-s intervals (0–20 s [T1], 21–40 s [T2], 41–60 s [T3]. Separate linear mixed effects models for each fluency task were used to determine the effects of group, time, and their interaction on word generation. Results: In both fluency tasks, word generation declined as a function of time. Individuals with MCI generated fewer words compared to controls during the first 20 s of phonemic (beta=−1.56; p<.001; d=0.28) and category fluency (beta=−1.85; p<.001; d=0.37). Group by time interactions revealed that individuals with MCI demonstrated attenuated declines in word generation from the first to the second and third time intervals of both phonemic ([T1 vs. T2] beta=2.17, p=.001; d=0.41; [T1 vs. T3]beta=2.28, p=.001; d=0.45) and category ([T1 vs. T2] beta= 2.22, p=.002; d=0.50; [T1 vs. T3]beta=3.16, p<.001; d=0.71) fluency. Conclusions: Early automatic retrieval processes in verbal fluency tasks are compromised in MCI. (JINS, 2017, 23, 44–55)

Objectives: The aim of this study was to characterize the neuropsychological profile of lifetime traumatic brain injury (TBI) in older Veterans. Methods: Participants were 169 older Veterans [mean age=79.1 years (range, 51–97 years), 89% male, 92% Caucasian], 88 with lifetime TBI and 81 without TBI, living in Veterans’ retirement homes in independent residence. TBI history was ascertained with the Ohio State TBI Identification Method structured interview. Cognition was assessed with neuropsychological tests: Raw scores were converted to Z-scores compared to age-corrected normative data and combined into five domain composite Z-scores (attention/working memory, learning/memory, language, processing speed, executive functioning). We investigated the association between TBI and performance in each cognitive domain in linear mixed effects models, with and without adjustment for demographics, medical comorbidities, and psychiatric variables. Results: Compared to those without TBI, older Veterans with TBI had greater deficits in processing speed (estimate=−.52; p=.01; f2=.08 in fully adjusted model) and executive functioning (estimate=−.41; p=.02; f2=.06 in fully adjusted model) but performed similarly in the attention/working memory, learning/memory, and language domains (all p>.05). TBI-associated deficits were most prominent among individuals with multiple mild TBIs and those with any moderate-to-severe TBI, but were not clearly present among those with single mild TBI. Conclusions: The neuropsychological profile of lifetime TBI in older Veterans is characterized by slowed processing speed and executive dysfunction, especially among those with greater injury burden. This pattern may reflect long-standing deficits or a TBI-associated cognitive decline process distinct from Alzheimer’s disease. (JINS, 2017, 23, 56–64)

Objectives: Concussion is defined as a complex pathophysiological process affecting the brain. Although the cumulative and long-term effects of multiple concussions are now well documented on cognitive and motor function, little is known about their effects on emotion recognition. Recent studies have suggested that concussion can result in emotional sequelae, particularly in females and multi-concussed athletes. The objective of this study was to investigate sex-related differences in emotion recognition in asymptomatic male and female multi-concussed athletes. Methods: We tested 28 control athletes (15 males) and 22 multi-concussed athletes (10 males) more than a year since the last concussion. Participants completed the Post-Concussion Symptom Scale, the Beck Depression Inventory-II, the Beck Anxiety Inventory, a neuropsychological test battery and a morphed emotion recognition task. Pictures of a male face expressing basic emotions (anger, disgust, fear, happiness, sadness, surprise) morphed with another emotion were randomly presented. After each face presentation, participants were asked to indicate the emotion expressed by the face. Results: Results revealed significant sex by group interactions in accuracy and intensity threshold for negative emotions, together with significant main effects of emotion and group. Conclusions: Male concussed athletes were significantly impaired in recognizing negative emotions and needed more emotional intensity to correctly identify these emotions, compared to same-sex controls. In contrast, female concussed athletes performed similarly to same-sex controls. These findings suggest that sex significantly modulates concussion effects on emotional facial expression recognition. (JINS, 2017, 23, 65–77)

Objectives: Cognitive-linguistic impairments in Parkinson’s disease (PD) have been well documented; however, few studies have explored the neurophysiological underpinnings of semantic deficits in PD. This study investigated semantic function in PD using event-related potentials. Methods: Eighteen people with PD and 18 healthy controls performed a semantic judgement task on written word pairs that were either congruent or incongruent. Results: The mean amplitude of the N400 for new incongruent word pairs was similar for both groups, however the onset latency was delayed in the PD group. Further analysis of the data revealed that both groups demonstrated attenuation of the N400 for repeated incongruent trials, as well as attenuation of the P600 component for repeated congruent trials. Conclusions: The presence of N400 congruity and N400 repetition effects in the PD group suggests that semantic processing is generally intact, but with a slower time course as evidenced by the delayed N400. Additional research will be required to determine whether N400 and P600 repetition effects are sensitive to further cognitive decline in PD. (JINS, 2017, 23, 78–89)

Objectives: Discrepant findings of age-related effects between cross-sectional and longitudinal studies on executive function (EF) have been described across different studies. The aim of the present study was to examine longitudinal age effects on inhibition and switching, two key subfunctions of EF, calculated from results on the Color Word Interference Test (CWIT). Methods: One hundred twenty-three healthy aging individuals (average age 61.4 years; 67% women) performed the CWIT up to three times, over a period of more than 6 years. Measures of inhibition, switching, and combined inhibition and switching were analyzed. A longitudinal linear mixed effects models analysis was run including basic CWIT conditions, and measures of processing speed, retest effect, gender, education, and age as predictors. Results: After taking all predictors into account, age added significantly to the predictive value of the longitudinal models of (i) inhibition, (ii) switching, and (iii) combined inhibition and switching. The basic CWIT conditions and the processing speed measure added to the predictive value of the models, while retest effect, gender, and education did not. Conclusions: The present study on middle-aged to older individuals showed age-related decline in inhibition and switching abilities. This decline was retained even when basic CWIT conditions, processing speed, attrition, gender, and education were controlled. (JINS, 2017, 23, 90–97)