Patterns of frontoparietal activation as a marker for unsuccessful visuospatial processing in healthy aging.

Visuospatial abilities are sensitive to age-related decline, although the neural basis for this decline (and its everyday behavioral correlates) is as yet poorly understood. fMRI was employed to examine age-related differences in patterns of functional activation that underlie changes in visuospatial processing. All participants completed a brief neuropsychological battery and also a figure ground task (FGT) assessing visuospatial processing while fMRI was recorded. Participants included 16 healthy older adults (OA; aged 69-82 years) and 16 healthy younger adults (YA; aged 20-35 years). We examined age-related differences in behavioral performance on the FGT in relation to patterns of fMRI activation. OA demonstrated reduced performance on the FGT task and showed increased activation of supramarginal parietal cortex as well as increased activation of frontal and temporal regions compared to their younger counterparts. Performance on the FGT related to increased supramarginal gyrus activity and increased medial prefrontal activity in OAs, but not YAs. Our results are consistent with an anterior-posterior compensation model. Successful FGT performance requires the perception and integration of multiple stimuli and thus it is plausible that healthy aging may be accompanied by changes in visuospatial processing that mimic a subtle form of dorsal simultanagnosia. Overall, decreased visuospatial processing in OA relates to an altered frontoparietal neurobiological signature that may contribute to the general phenomenon of increasingly fragmented execution of behavior associated with normal aging.

A new semantic list learning task to probe functioning of the Papez circuit.

INTRODUCTION: List learning tasks are powerful clinical tools for studying memory, yet have been relatively underutilized within the functional imaging literature. This limits understanding of regions such as the Papez circuit that support memory performance in healthy, nondemented adults. METHOD: The current study characterized list learning performance in 40 adults who completed a semantic list learning task (SLLT) with a Brown-Peterson manipulation during functional magnetic resonance imaging (fMRI). Cued recall with semantic cues and recognition memory were assessed after imaging. Internal reliability, convergent, and discriminant validity were evaluated. RESULTS: Subjects averaged 38% accuracy in recall (62% for recognition), with primacy but no recency effects observed. Validity and reliability were demonstrated by showing that the SLLT was correlated with the California Verbal Learning Test (CVLT), but not with executive functioning tests, and by high intraclass correlation coefficient across lists for recall (.91). fMRI measurements during encoding (vs. silent rehearsal) revealed significant activation in bilateral hippocampus, parahippocampus, and bilateral anterior and posterior cingulate cortex. Post hoc analyses showed increased activation in anterior and middle hippocampus, subgenual cingulate, and mammillary bodies specific to encoding. In addition, increasing age was positively associated with increased activation in a diffuse network, particularly frontal cortex and specific Papez regions for correctly recalled words. Gender differences were specific to left inferior and superior frontal cortex. CONCLUSIONS: This is a clinically relevant list learning task that can be used in studies of groups for which the Papez circuit is damaged or disrupted, in mixed or crossover studies at imaging and clinical sites.

Stress Response to the Functional Magnetic Resonance Imaging Environment in Healthy Adults Relates to the Degree of Limbic Reactivity during Emotion Processing.

BACKGROUND: Imaging techniques are increasingly being used to examine the neural correlates of stress and emotion processing; however, relations between the primary stress hormone cortisol, the functional magnetic resonance imaging (fMRI) environment, and individual differences in response to emotional challenges are not yet well studied. The present study investigated whether cortisol activity prior to, and during, an fMRI scan may be related to neural processing of emotional information. METHODS: Twenty-six healthy individuals (10 female) completed a facial emotion perception test during 3-tesla fMRI. RESULTS: Prescan cortisol was significantly correlated with enhanced amygdala, hippocampal, and subgenual cingulate reactivity for facial recognition. Cortisol change from pre- to postscanning predicted a greater activation in the precuneus for both fearful and angry faces. A negative relationship between overall face accuracy and activation in limbic regions was observed. CONCLUSION: Individual differences in response to the fMRI environment might lead to a greater heterogeneity of brain activation in control samples, decreasing the power to detect differences between clinical and comparison groups. © 2015 S. Karger AG, Basel.

Executive functioning and risk for Alzheimer's disease in the cognitively intact: Family history predicts Wisconsin Card Sorting Test performance.

OBJECTIVE: Alzheimer's disease (AD) research typically focuses on memory. However, executive functioning (EF) deficits are also common among AD patients; these deficits are associated with decreased functioning in activities of daily living, an important criterion in diagnosing AD. A classic test of EF ability, the Wisconsin Card Sort Test (WCST), has demonstrated sensitivity to differentiating individuals with AD from healthy controls, discriminating AD groups based on disease severity, and distinguishing AD from other types of dementia. Such sensitivity to AD raises the possibility that the WCST is also sensitive to very early, preclinical differences between those who have heightened risk for AD and those with lower risks. METHOD: The current study, therefore, examined WCST performance in healthy, cognitively intact older adults with a first-degree (i.e., sibling or parent) family history (FH) of AD (n = 18) and those with no such FH of AD (n = 24). RESULTS: Results revealed significant group differences for Categories Achieved, Percent Conceptual Level Responses, Total Errors, Perseverative Errors, and Non-Perseverative Errors, with the FH+ group consistently exhibiting poorer performance. Moreover, hierarchical regression analyses indicated that after accounting for age, sex, and education, FH significantly predicted all 5 of these variables. CONCLUSIONS: These results speak to the potential role of EF in bolstering the current understanding of early cognitive markers of future decline. Furthering what is known about the relationship between AD and nonmemory specific domains of cognition such as executive functioning may allow for better prediction of cognitive decline and potential progression to AD.

Physical activity reduces hippocampal atrophy in elders at genetic risk for Alzheimer's disease.

We examined the impact of physical activity (PA) on longitudinal change in hippocampal volume in cognitively intact older adults at varying genetic risk for the sporadic form of Alzheimer's disease (AD). Hippocampal volume was measured from structural magnetic resonance imaging (MRI) scans administered at baseline and at an 18-month follow-up in 97 healthy, cognitively intact older adults. Participants were classified as High or Low PA based on a self-report questionnaire of frequency and intensity of exercise. Risk status was defined by the presence or absence of the apolipoprotein E-epsilon 4 (APOE-ε4) allele. Four subgroups were studied: Low Risk/High PA (n = 24), Low Risk/Low PA (n = 34), High Risk/High PA (n = 22), and High Risk/Low PA (n = 17). Over the 18 month follow-up interval, hippocampal volume decreased by 3% in the High Risk/Low PA group, but remained stable in the three remaining groups. No main effects or interactions between genetic risk and PA were observed in control brain regions, including the caudate, amygdala, thalamus, pre-central gyrus, caudal middle frontal gyrus, cortical white matter (WM), and total gray matter (GM). These findings suggest that PA may help to preserve hippocampal volume in individuals at increased genetic risk for AD. The protective effects of PA on hippocampal atrophy were not observed in individuals at low risk for AD. These data suggest that individuals at genetic risk for AD should be targeted for increased levels of PA as a means of reducing atrophy in a brain region critical for the formation of episodic memories.