Frontotemporal neurofibrillary tangles and cerebrovascular lesions are associated with autism spectrum behaviors in late-life dementia

Background and objectives: The pathologic substrates or neuroanatomic regions responsible for similarities in behavioral features seen in autism spectrum disorder and late-life dementia remain unknown. The present study examined the neuropathologic features of late-life dementia in research volunteers with and without antemortem behaviors characteristic of autism spectrum disorders. Methods: Antemortem cross-sectional assessment of autistic spectrum behaviors proximal to death in persons with diagnosis of mild cognitive impairment or dementia was completed using the Gilliam Autism Rating Scale, 2nd edition (GARS-2), followed by postmortem quantitative and semiquantitative neuropathologic assessment. All individuals who completed the GARS-2 prior to autopsy were included (n = 56) and we note that no participants had known diagnosis of autism spectrum disorder. The GARS-2 was used as an antemortem screening tool to stratify participants into two groups: “Autism Possible/Very Likely” or “Autism Unlikely.” Data were analyzed using nonparametric statistics comparing location and scale to evaluate between-group differences in pathologic features. Results: Neurofibrillary tangles (NFT; p = 0.028) density and tau burden (p = 0.032) in the frontal region, the NFT density (p = 0.048) and neuritic plaque burden (p = 0.042), and the tau burden (p = 0.032) of the temporal region, were significantly different in scale between groups. For measures with significant group differences, the medians of the Autism Possible/Very Likely group were roughly equal to the 75th percentile of the Autism Unlikely group (i.e., the distributions were shifted to the right). Discussion: This study links behaviors characteristic of autism to increased pathologic tau burden in the frontal and temporal lobes in persons with late-life dementia. Additional studies are needed to determine causal factors and treatment options for behaviors characteristic of autism behaviors in late-life dementias.