Findings suggest that early psychiatric symptoms of emergent bvFTD may manifest as emotional blunting or mood changes not cleanly conforming to criteria for a DSM-defined mood disorder.
Objective:
The cognitive indicators of preclinical behavioral variant Frontotemporal Dementia (bvFTD) have not been identified. To investigate these indicators, we compared cross-sectional performance on a range of cognitive measures in 12 carriers of pathogenic MAPT mutations not meeting diagnostic criteria for bvFTD (i.e. preclinical) versus 32 demographically-matched familial non-carriers (n=44). Studying preclinical carriers offers a rare glimpse into emergent disease, environmentally and genetically contextualized through comparison to familial controls.
Methods:
Evaluating personnel blinded to carrier status administered a standardized neuropsychological battery assessing attention, speed, executive function, language, memory, spatial ability, and social cognition. Results from mixed effect modeling were corrected for multiplicity of comparison by the False Discovery Rate method, and results were considered significant at p<0.05. To control for potential interfamilial variation arising from enrollment of six families, family was treated as a random effect, while carrier status, age, gender, and education were treated as fixed effects.
Results:
Group differences were detected in 17 of 31 cognitive scores and spanned all domains except spatial ability. As hypothesized, carriers performed worse on specific measures of executive function, and social cognition, but also on measures of attention, speed, semantic processing, and memory storage and retrieval.
Conclusions:
Most notably, group differences arose on measures of memory storage, challenging long-standing ideas about the absence of amnestic features on neuropsychological testing in early bvFTD. Current findings provide important and clinically relevant information about specific measures that may be sensitive to early bvFTD, and advance understanding of neurocognitive changes that occur early in the disease.
Background: Apathy is a common and problematic symptom of several neurodegenerative illnesses, but its neuroanatomical bases are not understood. Objective: To determine the regions associated with apathy in subjects with mild Alzheimer's disease (AD) using a method that accounts for the significant co-linearity of regional atrophy and neuropsychiatric symptoms. Methods: We identified 57 subjects with mild AD (CDR = 1) and neuropsychiatric symptoms in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We performed a multivariate multiple regression with LASSO regularization on all symptom subscales of the Neuropsychiatric Inventory and the whole-brain ROI volumes calculated from their baseline MRIs with FreeSurfer. We compared our results to those from a previous study using the same method in patients with frontotemporal dementia (FTD) and corticobasal syndrome (CBS). Results: Of neuropsychiatric symptoms, apathy showed the most robust neuroanatomical associations in the AD subjects. Atrophy of the following regions were independently associated with apathy: the ventromedial prefrontal cortex; ventrolateral prefrontal cortex; posterior cingulate cortex and adjacent lateral cortex; and the bank of the superior temporal sulcus. These results replicate previous studies using FTD and CBS patients, mostly agree with the previous literature on apathy in AD, and correspond to the Medial and Orbital Prefrontal Cortex networks identified in non-human primates.
Conclusion:The current study, previous studies from our laboratory, and the previous literature suggest that impairment of the same brain networks involved in arousal, threat response, and reward processing are associated with apathy in AD and FTD.
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