Autistic spectrum behaviors in late‐life dementia are associated with an increased burden of neurofibrillary tangles in the frontal lobe

Abstract

AbstractBackgroundPrevious clinical studies have described autism spectrum‐like behaviors in approximately 16% of late‐onset dementia cases. The neuropathologic substrate for such behaviors is currently unknown, but may shed light on shared neuroanatomic and molecular pathways involved in these otherwise distinct forms of brain dysfunction. This study investigates the hypothesis that subjects with late onset dementia associated with autism‐like behaviors will exhibit increased pathologic features in both the frontal and parietal association cortices.MethodAn age, education, and gender‐matched case‐control design was used. Subjects were recruited from the University of Kentucky Alzheimer Disease Center longitudinal autopsy cohort. Subjects had a diagnosis of MCI or dementia at the time of completion of the Gilliam Autism Rating Scale‐2 (GARS‐2) in addition to standard clinical, genetic, and cognitive assessments (n = 148). Those who have come to autopsy demonstrating either no evidence of (n = 24) or a high level of (n = 19) autism‐like behaviors on the GARS‐2 were included. Comprehensive neuropathologic evaluation included assessment of all common late‐life dementia pathologies using both semiquantitative rating scales and digital quantitative measures of global and regional pathological features.ResultBetween group analyses demonstrated no significant differences in age, education, gender, clinical diagnosis, or apoE4 status. High‐autism vs. no‐autism cases scored significantly higher on the Clinical Dementia Rating scale (p < 0.05). Approximately 80% of cases had a primary pathologic diagnosis of Alzheimer’s disease, with the remaining 20% of individuals demonstrating pathologic features consistent with LATE (16%), cerebrovascular (2%), or Lewy body disease (2%). No cases had frontotemporal lobar degeneration (FTLD) as a primary or comorbid pathology. Quantitative measures of neurofibrillary tangles and tau burden were higher in the frontal lobes of high‐autism subjects compared to the matched no‐autism controls (p < 0.02).ConclusionThese data are the first to link autism‐like behaviors to increased levels of tau and neurofibrillary pathology in the frontal lobes at autopsy in subjects with late‐life dementia. Yet, the present data demonstrate that FTLD pathology is not a major contributor to such behaviors in a community‐based cohort of late‐life dementia. Further work understanding potential links between tau‐mediated neurodegeneration and autism‐like behavior is warranted.