Supplementary Material for: Dementia-Predicting Cognitive Risk Score and Its Correlation with Cortical Thickness in Parkinson Disease

<p><b><i>Background:</i></b> We developed a risk score system to predict risks of developing dementia in individual Parkinson disease (PD) patients using baseline neuropsychological tests. <b><i>Methods:</i></b> A total of 216 nondemented PD patients underwent a baseline neuropsychological evaluation and were followed up for a mean of 2.7 (±1.1) years. Univariate Cox regression models controlled for age, gender, and education selected neuropsychological tests individually predicting dementia risk. Then, a multivariate Cox regression model combined them into a cognitive risk score system. Cortical areas correlating with cognitive risk score were investigated using a separate MRI data set from 207 nondemented PD patients. <b><i>Results:</i></b> Fifty-two patients (23.9%) developed dementia. The univariate Cox regression analyses identified the confrontational naming and semantic fluency tests, frontal/executive function tests, immediate verbal memory test, and visuospatial function test as predicting dementia risk. The calculated cognitive risk score (range 53-188) predicted future dementia with moderate accuracy (integrated area under the curve = 0.79; 95% CI: 0.73-0.85). A higher cognitive risk score correlated with cortical thinning in the right anteromedial temporal cortex, bilateral posterior cingulate cortex, right anterior cingulate cortex, left parahippocampal gyrus, and right superior frontal cortex in a separate MRI data set. <b><i>Conclusion:</i></b> The cognitive risk score system is a useful approach to predict the dementia risk among PD patients.</p

Supplementary Material for: Genetic Variation in Genes Underlying Diverse Dementias May Explain a Small Proportion of Cases in the Alzheimer’s Disease Sequencing Project

<b><i>Background/Aims:</i></b> The Alzheimer’s Disease Sequencing Project (ADSP) aims to identify novel genes influencing Alzheimer’s disease (AD). Variants within genes known to cause dementias other than AD have previously been associated with AD risk. We describe evidence of co-segregation and associations between variants in dementia genes and clinically diagnosed AD within the ADSP. <b><i>Methods:</i></b> We summarize the properties of known pathogenic variants within dementia genes, describe the co-segregation of variants annotated as “pathogenic” in ClinVar and new candidates observed in ADSP families, and test for associations between rare variants in dementia genes in the ADSP case-control study. The participants were clinically evaluated for AD, and they represent European, Caribbean Hispanic, and isolate Dutch populations. <b><i>Results/Conclusions:</i></b> Pathogenic variants in dementia genes were predominantly rare and conserved coding changes. Pathogenic variants within <i>ARSA</i>, <i>CSF1R</i>, and <i>GRN</i> were observed, and candidate variants in <i>GRN</i> and <i>CHMP2B</i> were nominated in ADSP families. An independent case-control study provided evidence of an association between variants in <i>TREM2</i>, <i>APOE</i>, <i>ARSA</i>, <i>CSF1R</i>, <i>PSEN1</i>, and <i>MAPT</i> and risk of AD. Variants in genes which cause dementing disorders may influence the clinical diagnosis of AD in a small proportion of cases within the ADSP