Antemortem prediction of dementia-causing neurodegenerative disease is challenging, in part due to the frequency of co-occurring diseases. Etiologic diagnosis may be aided by the identification of highly specific clinical features or available biomarkers. Here we present an educational case of an individual with a primary neuropathological diagnosis of lewy body disease (LBD) and contributing progressive supranuclear palsy (PSP). He was clinically diagnosed only with PSP-Richardson syndrome based on ocular motor findings. LBD was not considered despite several inconsistent clinical features. Neuropathological examination showed well-developed transitional/limbic LBD and a very mild burden of PSP. Diagnostic criteria for PSP were just met based on semiquantitative ratings and affected neuroanatomy. No amyloid plaques of Alzheimer disease (AD) were identified, but AD-tau tangles reached Braak stage 4. Postmortem analysis of cerebrospinal fluid showed alpha-synuclein seeding amplification, but no clear evidence for AD. However, plasma biomarkers P-tau181 and P-tau217 suggested AD neuropathological change. Biomarkers may assist in the assessment of multiple etiologies, but they are imperfect and require expert interpretation within clinical contexts. Accurate etiologic prediction requires an understanding of common co-occurring neurodegenerative diseases, cautious interpretation of biomarkers, and knowledge of clinicopathological relationships.
Background: Mild cognitive impairment (MCI) is common in older adults and may progress to Alzheimer disease. Accessible behavioral measures are needed to identify subtle cognitive changes; tactile tasks may provide a low-cost approach. Objective: To examine whether tactile cognitive tasks can differentiate between older adults with MCI and healthy controls (HC), and to explore whether processing related to working memory may contribute to tactile task deficits. Methods: We recruited two independent cohorts of older adults. Cohort 1 completed a tactile angle size comparison task and a tactile angle sequencing task, while Cohort 2 completed a visual learning-recognition task. We analyzed group differences while controlling for age, sex, years of education, and scores on the Hamilton Anxiety Scale and Hamilton Depression Scale. We then calculated signal detection indices for the learning-recognition task. Results: After covariate adjustment, the tactile angle size comparison task did not show a significant group difference ( p =0.388). The tactile angle sequencing task significantly distinguished individuals with MCI from HC ( p <0.001). Receiver operating characteristic analyses showed acceptable-to-good discriminatory performance for the tactile tasks, with stronger performance for the sequencing task. In the learning-recognition task, individuals with MCI showed reduced discrimination sensitivity indexed by d ′. Conclusion: Tactile sequencing performance appears more sensitive to MCI-related impairment than simple tactile angle comparison. These findings suggest that complex tactile deficits in MCI may be partly associated with working-memory–related processing.
Background: Treatment with transcranial direct current stimulation (tDCS) has resulted in language improvements in a variety of populations. Objective: To determine the feasibility of tDCS in adolescents with autism spectrum disorder (ASD) and to examine fMRI activation changes associated with tDCS. To provide preliminary information on whether the left or right inferior frontal gyrus (IFG) is a better target for language improvement. Methods: We applied anodal tDCS to the left or right IFG in eight adolescents (11–17 years) with ASD and examined changes in fluency and fMRI activation during a semantic task. Results: tDCS was well tolerated and all participants were able to complete the session. Of the participants who received right tDCS, 67% (2/3) showed improvements in letter and category fluency. None of the participants who received left tDCS showed improvement in both letter and category fluency. We were unable to collect two usable fMRI scans forhalf of the participants. Individual fMRI activation data did not produce reliable results regarding tDCS-induced changes. Conclusion: Our preliminary results add to findings suggesting tDCS is feasible in adolescents with ASD, including those with severely impaired language abilities. Right IFG stimulation should be investigated in a larger population, as our pilot findings suggest slightly greater improvement in language fluency relative to left IFG stimulation. It may not be practical or reliable to use fMRI to evaluate the effectiveness of tDCS in individuals with ASD.
