Michael Stepanovic

Youthful Brains in Older Adults: Preserved Neuroanatomy in the Default Mode and Salience Networks Contributes to Youthful Memory in Superaging

Decline in cognitive skills, especially in memory, is often viewed as part of “normal” aging. Yet some individuals “age better” than others. Building on prior research showing that cortical thickness in one brain region, the anterior midcingulate cortex, is preserved in older adults with memory performance abilities equal to or better than those of people 20–30 years younger (i.e., “superagers”), we examined the structural integrity of two large-scale intrinsic brain networks in superaging: the default mode network, typically engaged during memory encoding and retrieval tasks, and the salience network, typically engaged during attention, motivation, and executive function tasks. We predicted that superagers would have preserved cortical thickness in critical nodes in these networks. We defined superagers (60–80 years old) based on their performance compared to young adults (18–32 years old) on the California Verbal Learning Test Long Delay Free Recall test. We found regions within the networks of interest where the cerebral cortex of superagers was thicker than that of typical older adults, and where superagers were anatomically indistinguishable from young adults; hippocampal volume was also preserved in superagers. Within the full group of older adults, thickness of a number of regions, including the anterior temporal cortex, rostral medial prefrontal cortex, and anterior midcingulate cortex, correlated with memory performance, as did the volume of the hippocampus. These results indicate older adults with youthful memory abilities have youthful brain regions in key paralimbic and limbic nodes of the default mode and salience networks that support attentional, executive, and mnemonic processes subserving memory function. SIGNIFICANCE STATEMENT Memory performance typically declines with age, as does cortical structural integrity, yet some older adults maintain youthful memory. We tested the hypothesis that superagers (older individuals with youthful memory performance) would exhibit preserved neuroanatomy in key brain networks subserving memory. We found that superagers not only perform similarly to young adults on memory testing, they also do not show the typical patterns of brain atrophy in certain regions. These regions are contained largely within two major intrinsic brain networks: the default mode network, implicated in memory encoding, storage, and retrieval, and the salience network, associated with attention and executive processes involved in encoding and retrieval. Preserved neuroanatomical integrity in these networks is associated with better memory performance among older adults.

COMPARISON OF HYPOMETABOLISM AND CORTICAL ATROPHY IN PRIMARY PROGRESSIVE APHASIA

functional magnetic resonance imaging (fMRI). The current study investigated differences in resting-state connectivity between AD patients with and without delusions.Methods:10 AD patients with delusions and 11 AD patients without delusions underwent fMRI scanning in a 3 Tesla scanner. The resting-state functional connectivity was assessed by parcellating the brain using a data-drivenmethod based on kmeans clustering, and measuring functional connectivity for frontal clusters, associated with cognitive control. The presence of delusions was evaluated using the Neuropsychiatric Inventory Questionnaire completed by an informant. Results:There were no significant differences in age, education, or global cognition as measured by the Montreal Cognitive Assessment (MoCA) between delusional and nondelusional groups. None of the delusional patients were on antipsychoticmedication. A single cluster of interest was analyzed, consisting of the superior medial frontal gyrus and the anterior cingulate. A twosample t-test found significantly increased connectivity (p<0.05, cluster size thresholded) between these regions of interest and the superior frontal gyrus in delusional compared to non-delusional patients. Conclusions:Our results suggest that aberrant resting-state connectivity between frontal regions may be related to the pathophysiology of delusions in Alzheimer’s disease. It is possible that altered frontal connectivity may be the brain trying to integrate disorganized neural processes, which can give rise to delusions[1]. The findings resemble resting-state abnormalities observed in patients with schizophrenia with delusions, with reports showing increased connectivity between the anterior cingulate gyrus (ACC) and medial frontal gyrus [2, 3].

Atrophy in distinct corticolimbic networks subserving social-affective behavior in semantic-variant primary progressive aphasia

OBJECTIVE : Semantic-variant Primary Progressive Aphasia(svPPA) is a neurodegenerative disorder with core impairments in semantic memory. Although many svPPA patients also exhibit symptoms involving social-emotional behavior, these have received relatively little study. We investigated atrophy in large-scale brain networks subserving social-emotional behaviors in svPPA compared to controls. BACKGROUND : We previously defined three social-emotional brain networks in healthy subjects. The perception network guiding detection/interpretation of social sensory cues includes the fusiform gyrus, ventral temporal pole, superior temporal sulcus and lateral orbitofrontal cortex. The affiliation network facilitating prosocial behaviors includes the ventromedial prefrontal, subgenual and rostral anterior cingulate cortices, dorsal temporal pole, hippocampus, parahippocampus, entorhinal cortex and nucleus accumbens. The aversion network mediating avoidant behaviors includes the insula, caudal anterior cingulate cortex and putamen. These networks are linked to amygdalar subregions. We hypothesized that these three networks would exhibit atrophy in svPPA and relate to socioemotional impairment. DESIGN/METHODS : Seventeen svPPA subjects and thirty age-and-gender matched controls were studied. T1-weighted MPRAGE MRI scans were acquired, and FreeSurfer software was used to process data and extract cortical thickness or volumetric data across a priori regions-of-interest. Findings were statistically significant at p≤0.005 to correct for multiple comparisons. The types and severity of social symptoms were rated using the Social Impairment Rating Scale (SIRS). RESULTS : svPPA subjects showed left-lateralized perception(z-score=-4.729; p<0.0001) and affiliation(z-score=-3.483; p=0.0005) network atrophy. Trends toward bilateral amygdala and right perception network atrophy were also observed. Left affiliation network atrophy correlated with SIRS socioemotional detachment sub-scores(r=0.56; p=0.037). The aversion network and control networks (mentalizing and mirror networks) did not show statistically significant atrophy. CONCLUSIONS : svPPA patients demonstrated left-lateralized perception and affiliation network atrophy which may provide the biological basis for social-emotional deficits in these patients. Future symptom-specific analyses may further clarify these brain-behavior relationships. Study Supported by: R21 NS077059, R21 MH097094, and R25 NS065743-05S1. Disclosure: Dr. Perez has nothing to disclose. Dr. Makaretz has nothing to disclose. Dr. Caso has nothing to disclose. Dr. Stepanovic has nothing to disclose. Dr. Brickhouse has nothing to disclose. Dr. Quimby has nothing to disclose. Dr. Hochberg has nothing to disclose. Dr. Xia has nothing to disclose. Dr. Dickerson has received personal compensation for activities with Pfizer, Inc., En Vivo, and Merck.