Differentiating among stages of cognitive impairment in aging: Version 3 of the Uniform Data Set (UDS) neuropsychological test battery and MoCA index scores

Introduction: Federally funded Alzheimer\u27s Disease Centers in the United States have been using a standardized neuropsychological test battery as part of the National Alzheimer\u27s Coordinating Center Uniform Data Set (UDS) since 2005. Version 3 (V3) of the UDS replaced the previous version (V2) in 2015. We compared V2 and V3 neuropsychological tests with respect to their ability to distinguish among the Clinical Dementia Rating (CDR) global scores of 0, 0.5, and 1. Methods: First, we matched participants receiving V2 tests (V2 cohort) and V3 tests (V3 cohort) in their cognitive functions using tests common to both versions. Then, we compared receiver-operating characteristic (ROC) area under the curve in differentiating CDRs for the remaining tests. Results: Some V3 tests performed better than V2 tests in differentiating between CDR 0.5 and 0, but the improvement was limited to Caucasian participants. Discussion: Further efforts to improve the ability for early identification of cognitive decline among diverse racial groups are required

Validation of AD8-Philippines (AD8-P): A brief informant-based questionnaire for dementia screening in the Philippines

Aim: This study was aimed at validating the Filipino version of AD8 (AD8-P). Methods: Community-dwelling Filipino older persons aged ≥60 years, together with their informants, participated in this study. Psychologists independently interviewed the informants with AD8-P and administered the Filipino-validated Mini-Mental State Examination (MMSE-P) and Montreal Cognitive Assessment (MoCA-P) to the older persons. Neurologists and geriatrician conducted physical and neurological examination and Clinical Dementia Rating™ (CDR™) to determine cognitive diagnosis and were blinded with the results of AD8-P. Dementia was diagnosed based on DSM-IV-TR criteria. AD8-P discriminatory ability to screen for dementia was evaluated according to DSM-IV-TR diagnostic criteria for dementia. Results: A total of 366 community-dwelling Filipino older persons aged ≥60 years, 213 with normal cognition and 153 with dementia, and their informants were included in this study. Majority (90%) were at the mildest stage of dementia. Area under the receiver-operating-characteristic curve (AUROC) for AD8-P was 0.94 (95% CI 0.92 to 0.96), demonstrating excellent overall predictive power to screen for dementia. The optimal AD8-P cut-off score with best balance sensitivity (91.5%) and specificity (77.9%) was ≥3. Conclusion: AD8-P demonstrated good psychometric properties to screen for dementia, even at the earliest stage of cognitive decline

Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is a clinically heterogeneous disorder with a substantial burden on healthcare. Despite this, the genetic basis of the disorder is not well defined and its boundaries with other neurodegenerative diseases are unclear. Here, we performed whole exome sequencing of a cohort of 1118 Caucasian DLB patients, and focused on genes causative of monogenic neurodegenerative diseases. We analyzed variants in 60 genes implicated in DLB, Alzheimer\u27s disease, Parkinson\u27s disease, frontotemporal dementia, and atypical parkinsonian or dementia disorders, in order to determine their frequency in DLB. We focused on variants that have previously been reported as pathogenic, and also describe variants reported as pathogenic which remain of unknown clinical significance, as well as variants associated with strong risk. Rare missense variants of unknown significance were found in APP, CHCHD2, DCTN1, GRN, MAPT, NOTCH3, SQSTM1, TBK1 and TIA1. Additionally, we identified a pathogenic GRN p.Arg493* mutation, potentially adding to the diversity of phenotypes associated with this mutation. The rarity of previously reported pathogenic mutations in this cohort suggests that the genetic overlap of other neurodegenerative diseases with DLB is not substantial. Since it is now clear that genetics plays a role in DLB, these data suggest that other genetic loci play a role in this disease