Differential Vulnerability of Hippocampal Subfields to Amyloid and Tau Deposition in the Lewy Body Diseases.

BACKGROUND AND OBJECTIVES: Alzheimer disease (AD) copathologies of ß-amyloid and tau are common in the Lewy body diseases (LBD), dementia with Lewy bodies (DLB) and Parkinson disease (PD), and target distinct hippocampal subfields compared with Lewy pathology, including subiculum and CA1. We investigated the hypothesis that AD copathologies impact the pattern of hippocampal subregion volume loss and cognitive function in LBD. METHODS: This was a cross-sectional and longitudinal, single-center, observational cohort study. Participants underwent neuropsychological testing and 3T-MRI with hippocampal segmentation using FreeSurferV7. PiB-PET and flortaucipir-PET imaging of comorbid ß-amyloid (A) and tau (T) were acquired. The association of functional cognition, ß-amyloid, and tau loads with hippocampal subregion volume was assessed. The contribution of subregion volumes to the relationship of AD-related deposits on functional cognition was examined with mediation analysis. The effects of AD-related deposits on the rate of subregion atrophy were evaluated with mixed-effects models. RESULTS: Of 103 participants (mean age: 70.3 years; 37.3% female), 52 had LBD with impaired cognition (LBD-I), 26 had normal cognition (LBD-N), and 25 were A- healthy controls (HCs). Volumes of hippocampal subregions prone to AD copathologies, including subiculum (F = 6.9, p = 0.002), presubiculum (F = 7.3, p = 0.001), and parasubiculum (F = 5.9, p = 0.004), were reduced in LBD-I compared with LBD-N and HC. Volume was preserved in CA2/3, Lewy pathology susceptible subregions. In LBD-I, reduced CA1, subiculum, and presubiculum volumes were associated with greater functional cognitive impairment (all p < 0.05). Compared with HC, subiculum volume was reduced in A+T+ but not A-T- participants (F = 2.62, p = 0.043). Reduced subiculum volume mediated the effect of amyloid on functional cognition (0.12, 95% CI: 0.005 to 0.26, p = 0.040). In 26 longitudinally-evaluated participants, baseline tau deposition was associated with faster CA1 (p = 0.021) and subiculum (p = 0.002) atrophy. DISCUSSION: In LBD, volume loss in hippocampal output subregions-particularly the subiculum-is associated with functional cognition and AD-related deposits. Tau deposition appears to accelerate subiculum and CA1 atrophy, whereas Aß does not. Subiculum volume may have value as a biomarker of AD copathology-mediated neurodegeneration and disease progression.

Health phenome of Parkinson's patients reveals prominent mood-sleep cluster.

Background: Associations between phenotypic traits, environmental exposures, and Parkinson's disease have largely been evaluated one-by-one, piecemeal, and pre-selections. A comprehensive picture of comorbidities, phenotypes, exposures, and polypharmacy characterizing the complexity and heterogeneity of real-world patients presenting to academic movement disorders clinics in the US is missing. Objectives: To portrait the complexity of features associated with patients with Parkinson's disease in a study of 933 cases and 291 controls enrolled in the Harvard Biomarkers Study. Methods: The primary analysis evaluated 64 health features for associations with Parkinson's using logistic regression adjusting for age and sex. We adjusted for multiple testing using the false discovery rate (FDR) with £ 0.05 indicating statistical significance. Exploratory analyses examined feature correlation clusters and feature combinations. Results: Depression (OR = 3.11, 95% CI 2.1 to 4.71), anxiety (OR = 3.31, 95% CI 2.01-5.75), sleep apnea (OR 2.58, 95% CI 1.47-4.92), and restless leg syndrome (RLS; OR 4.12, 95% CI 1.81-12.1) were significantly more common in patients with Parkinson's than in controls adjusting for age and sex with FDR £ 0.05. The prevalence of depression, anxiety, sleep apnea, and RLS were correlated, and these diseases formed part of a larger cluster of mood traits and sleep traits linked to PD. Exposures to pesticides (OR 1.87, 95% CI 1.37-2.6), head trauma (OR 2.33, 95% CI 1.51-3.73), and smoking (OR 0.57, 95% CI 0.43-0.75) were significantly associated with the disease consistent with previous studies. Vitamin supplementation with cholecalciferol (OR 2.18, 95% CI 1.4-3.45) and coenzyme Q10 (OR 2.98, 95% CI 1.89-4.92) was more commonly used by patients than controls. Cumulatively, 43% (398 of 933) of Parkinson's patients had at least one psychiatric or sleep disorder, compared to 21% (60 of 291) of healthy controls. Conclusions: 43% of Parkinson's patients seen at Harvard-affiliated teaching hospitals have depression, anxiety, and disordered sleep. This syndromic cluster of mood and sleep traits may be pathophysiologically linked and clinically important.