Objectives: The purpose of this study was to investigate the longitudinal trajectory of self- and informant-subjective cognitive complaints (SCC), and to determine if SCC predict longitudinal changes in objective measures (OM) of cognitive function. Methods: The study included healthy and cognitively normal late middle-aged adults enriched with a family history of AD who were evaluated at up to three visits over a 4-year period. At each visit (Visit 1–3), self- and informant-SCC and OM were evaluated. Linear mixed models were used to determine if the longitudinal rate of change of self- and informant-SCC were associated with demographic variables, depressive symptoms, family history (FH), and apolipoprotein epsilon 4 (APOE4) status. The same modeling approach was used to examine the effect of Visit 1 SCC on longitudinal cognitive change after controlling for the same variables. Results: At Visit 1, more self-SCC were associated with fewer years of education and more depressive symptoms. SCC were also associated with poorer performance on cognitive measures, such that more self-SCC at Visit 1 were associated with poorer performance on memory and executive functioning measures at Visit 1, while more informant-SCC were associated with faster rate of longitudinal decline on a measure of episodic learning and memory. FH and APOE4 status were not associated with SCC. Discussion: Self- and informant-SCC showed an association with OM, albeit over different time frames in our late middle-aged sample. Additional longitudinal follow-up will likely assist in further clarifying these relationships as our sample ages and more pronounced cognitive changes eventually emerge. (JINS, 2017, 23, 617–626)

Objectives: Although evidence exists of broadly defined memory impairment among adolescents with critical congenital heart disease (CHD), nuanced investigations of declarative memory in this at-risk population have not been conducted. This study had two primary aims: (1) to conduct a fine-grained analysis of a range of relevant learning and memory processes in adolescents with critical biventricular CHD, and (2) to identify risk, odds, and predictors of memory impairment. Methods: Data were combined from two single-center studies of neurodevelopmental outcomes in critical CHD. Two-hundred seven adolescents (M age =15.61±1.0 years) with critical CHD (139 with dextro-transposition of the great arteries and 68 with tetralogy of Fallot without an identified genetic condition), as well as 61 healthy referents (M age =15.27±1.1 years) completed a neuropsychological evaluation which included the Children’s Memory Scale. Results: Whereas visual-spatial memory deficits were found in both CHD subgroups, verbal memory abilities were relatively preserved. Adolescents with CHD demonstrated stronger memory for Stories than Word Pairs, t (203)=2.63, p=.009, and for Dot Locations than Faces, t(204)=−2.57, p=.01. CHD subgroup, socioeconomic status, sex, and seizure history were among the most frequent significant predictors of memory impairment. Seizure history, in particular, was associated with a 2 to 3 times greater odds of impaired performance on learning and memory tasks. Conclusions: Adolescents with critical biventricular CHD are at risk for deficits in aspects of declarative memory. Independent risk factors for worse outcome include history of seizures. (JINS, 2017, 23, 627–639)

Objectives: The present study examined differences in neurocognitive outcomes among non-Hispanic Black and White stroke survivors using the NIH Toolbox-Cognition Battery (NIHTB-CB), and investigated the roles of healthcare variables in explaining racial differences in neurocognitive outcomes post-stroke. Methods: One-hundred seventy adults (91 Black; 79 White), who participated in a multisite study were included (age: M=56.4; SD=12.6; education: M=13.7; SD=2.5; 50% male; years post-stroke: 1–18; stroke type: 72% ischemic, 28% hemorrhagic). Neurocognitive function was assessed with the NIHTB-CB, using demographically corrected norms. Participants completed measures of socio-demographic characteristics, health literacy, and healthcare use and access. Stroke severity was assessed with the Modified Rankin Scale. Results: An independent samples t test indicated Blacks showed more neurocognitive impairment (NIHTB-CB Fluid Composite T-score: M=37.63; SD=11.67) than Whites (Fluid T-score: M=42.59, SD=11.54; p=.006). This difference remained significant after adjusting for reading level (NIHTB-CB Oral Reading), and when stratified by stroke severity. Blacks also scored lower on health literacy, reported differences in insurance type, and reported decreased confidence in the doctors treating them. Multivariable models adjusting for reading level and injury severity showed that health literacy and insurance type were statistically significant predictors of the Fluid cognitive composite (p<.001 and p=.02, respectively) and significantly mediated racial differences on neurocognitive impairment. Conclusions: We replicated prior work showing that Blacks are at increased risk for poorer neurocognitive outcomes post-stroke than Whites. Health literacy and insurance type might be important modifiable factors influencing these differences. (JINS, 2017, 23, 640–652)

Objectives: Multiple sclerosis (MS) can be associated with impaired social cognition. However, social cognition skills have never been explored in the different subtypes of MS. The first aim of this study was to examine whether MS subtypes differ on the course of social cognition. The second aim was to explore the relationship between social cognition performances and executive abilities and mood variables. Methods: Sixty-two patients with MS and 33 healthy matched controls performed experimental tasks assessing facial emotion recognition, theory of mind (ToM), and cognitive functioning, in particular executive functions. Results: Patients differed from controls on both measures of social cognition. On the ToM measures, patients with progressive MS scored significantly lower than healthy participants. Patients with primary progressive MS performed worse than both healthy participants and patients with relapsing-remitting MS on the recognition of fearful facial expressions, while patients with secondary progressive MS performed worse on the recognition of facial expressions of sadness. Patients’ social cognition difficulties were correlated with processing speed, working memory, and verbal fluency. Conclusions: These preliminary results suggested that there may be qualitative differences in social cognition difficulties among the phenotypes. Furthermore, these impairments were related to executive functions, but unrelated to patients’ disability or level of depression. These data highlight the need for research to determine the real impact of these deficits on interpersonal relationships among patients and to confirm these disorders in a larger population with progressive forms of MS. (JINS, 2017, 23, 653–664)

Objectives: In unpredictable situations, individuals often show tradeoffs between response initiation and inhibition speeds. We tested the hypothesis that Parkinson’s disease (PD) motor subtypes differentially impact tradeoffs between these two action-oriented processes. We predicted that, compared to tremor dominant (TD) patients, predominant postural instability and gait dysfunction (PIGD) patients would show exacerbated tradeoffs between response initiation and inhibition in situations requiring the sudden potential need to interrupt an action. Methods: Fifty-one PD patients (subdivided into PIGD [n=27] and TD [n=24]) and 21 healthy controls (HCs) completed a choice reaction task to establish baseline response initiation speed between groups. Subsequently, participants completed a stop-signal task which introduced an occasional, unpredictable stop stimulus. We measured changes in initiation speed in preparation of an unpredictable stop (i.e., proactive slowing) and inhibition latency (i.e., stop-signal reaction time). Results: Compared to HCs, PD patients showed slower response initiation speeds in the choice reaction task. All groups showed proactive slowing in the stop-signal task but the magnitude was considerably larger in PIGD patients, almost twice as large as TD patients. PD patients, irrespective of motor subtype, showed longer inhibition latencies than HCs. Conclusions: PIGD and TD subtypes both showed exacerbated response inhibition deficits. However, PIGD patients showed much more pronounced proactive slowing in situations with an expected yet unpredictable need to stop action abruptly. This suggests that PIGD is accompanied by exaggerated tradeoffs between response initiation and inhibition processes to meet situational action demands. We discuss putative neural mechanisms and clinical implications of these findings. (JINS, 2017, 23, 665–674)

Objectives: Executive dysfunction is a common feature in Parkinson’s disease (PD). However, there is a lack of brief validated instruments for executive dysfunction in PD. Methods: The aim of the present study was to assess the relation of Frontal Assessment Battery (FAB) scores to age and education, to verify the utility of FAB in the evaluation of executive dysfunction in PD and to differentiate between controls (n=41), PD patients with normal cognition (PD-NC; n=41; Hoehn and Yahr stages 2–3) and PD with mild cognitive impairment (PD-MCI; n=32; Hoehn and Yahr stages 2–3). In addition, we studied the relation between voxel-based morphometric (VBM) data and FAB results in PD. Results: We found that FAB scores are significantly related to age and education. The FAB has shown discriminative validity for the differentiation of PD-MCI from PD-NC and controls (area under the curve >.80). Also, the VBM analysis revealed lower FAB scores are specifically related to lower gray matter density in the right ventromedial prefrontal areas and precuneus. Conclusions: The FAB can be recommended as a valid instrument for PD-MCI Level I screening. FAB is sensitive to frontal lobe involvement in PD as reflected by lower gray matter density in prefrontal areas. (JINS, 2017, 23, 675–684)

Objectives: Two theories of tool use, namely the gesture engram and the technical reasoning theories, make distinct predictions about the involvement of the left inferior parietal lobe (IPL) in manipulation judgement tasks. The objective here is to test these alternative predictions based on previous studies on manipulation judgment tasks using transcranial magnetic stimulations (TMS) targeting the left supramarginal gyrus (SMG). Methods: We review recent TMS studies on manipulation judgement tasks and confront these data with predictions made by both tool use theories. Results: The left SMG is a highly intertwined region, organized following several functionally distinct areas and TMS may have disrupted a cortical network involved in the ability to use tools rather than only one functional area supporting manipulation knowledge. Moreover, manipulation judgement tasks may be impaired following virtual lesions outside the IPL. Conclusions: These data are more in line with the technical reasoning hypothesis, which assumes that the left IPL does not store manipulation knowledge per se. (JINS, 2017, 23, 685–691)

Objectives: Mental arithmetic is essential to daily life. Researchers have explored the mechanisms that underlie mental arithmetic. Whether mental arithmetic fact retrieval is dependent on surface modality or knowledge format is still highly debated. Chinese individuals typically use a procedure strategy for addition; and they typically use a rote verbal strategy for multiplication. This provides a way to examine the effect of surface modality on different arithmetic operations. Methods: We used a series of neuropsychological tests (i.e., general cognitive, language processing, numerical processing, addition, and multiplication in visual and auditory conditions) for a patient who had experienced a left frontotemporal stroke. Results: The patient had language production impairment; but preserved verbal processing concerning basic numerical abilities. Moreover, the patient had preserved multiplication in the auditory presentation rather than in the visual presentation. The patient suffered from impairments in an addition task, regardless of visual or auditory presentation. Conclusions: The findings suggest that mental multiplication could be characterized as a form of modality-dependent processing, which was accessed through auditory input. The learning strategy of multiplication table recitation could shape the verbal memory of multiplication leading to persistence of the auditory module. (JINS, 2017, 23, 692–699)

Objectives: Dysbiosis of the gut microbiome is implicated in numerous human health conditions. Animal studies have linked microbiome disruption to changes in cognitive functioning, although no study has examined this possibility in neurologically healthy older adults. Methods: Participants were 43 community-dwelling older adults (50–85 years) that completed a brief cognitive test battery and provided stool samples for gut microbiome sequencing. Participants performing≥1 SD below normative performance on two or more tests were compared to persons with one or fewer impaired scores. Results: Mann Whitney U tests revealed different distributions of Bacteroidetes (p=.01), Firmicutes (p=.02), Proteobacteria (p=.04), and Verrucomicrobia (p=.003) between Intact and Impaired groups. These phyla were significantly correlated with cognitive test performances, particularly Verrucomicrobia and attention/executive function measures. Conclusions: The current findings suggest that composition of the gut microbiome is associated with cognitive test performance in neurologically healthy older adults. Future studies are needed to confirm these findings and explore possible mechanisms. (JINS, 2017, 23, 700–705)