| Predicted Trait | |
| Reported Trait | Parkinson's disease dementia |
| Mapped Trait(s) | |
| Score Construction | |
| PGS Name | PHS3_PDD |
| Development Method | |
| Name | Variants associated with Parkinson's disease |
| Parameters | Lead variant associated with Parkinsons disease dementia in each prognosis loci |
| Variants | |
| Original Genome Build | hg19 |
| Number of Variants | 3 |
| Effect Weight Type | log(HR) |
| PGS Source | |
| PGS Catalog Publication (PGP) ID | PGP000181 |
| Citation (link to publication) | Liu G et al. Nat Genet (2021) |
| Ancestry Distribution | |
| Source of Variant Associations (GWAS) | |
| Score Development/Training | |
| PGS Evaluation | |
| Study Identifiers | Sample Numbers | Sample Ancestry | Cohort(s) |
|---|---|---|---|
Europe PMC: 33958783 |
2,650 individuals | European, NR | 10 cohorts
|
| Study Identifiers | Sample Numbers | Sample Ancestry | Cohort(s) | Phenotype Definitions & Methods | Age of Study Participants | Participant Follow-up Time | Additional Ancestry Description | Additional Sample/Cohort Information |
|---|---|---|---|---|---|---|---|---|
| — | 3,821 individuals | European, NR | 13 cohorts
|
All individuals had Parkinsons' disease. Dementia was defined by the following criteria for each cohort. HBS: Dementia was defined using operationalized level 1 MDS dementia criteria. These criteria required 1, an MMSE < 26; 2, cognitive deficits severe enough to impact daily living (UPDRS sub-score I item 1, Intellectual impairment score ≥ 2 indicating ‘Dementia has impact on active daily living scale’); 3, impairment in at least two cognitive domains operationalized as impairment in two of the following four tasks: ≤ 3 of 5 points in the MMSE Seven backward test (attention); abnormal clock drawing test (executive dysfunction); subscore = 0 in the MMSE Pentagons (visuo-constructive ability); and ≤ 2 of 3 points in the 3-Word Recall of the MMSE (memory performance). A Geriatric Depression Scale-15 (GDS-15) score <10 was used to indicate the absence of severe depression. NET-PD & PROPARK: Diagnosis of dementia was based on a SCOPA-COG cut-off value of 22/23. DIGPD: Dementia was defined using the diagnostic criteria and checklist recommended for the diagnosis of PDD by the Movement Disorder task force as well as interview-based assessments with the patient and caregiver. CamPaIGN: Dementia was diagnosed on the basis of a MMSE of less than or equal to 24 and fulfillment of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for dementia. PICNICS: Dementia was diagnosed using level 1 MDS dementia criteria, which were operationalized in this cohort using the Addenbrooke's Cognitive Examination-Revised, tests of semantic and phonemic fluency, and the pentagon copying test as well as interview-based assessments with the patient and caregiver. PDBP: Dementia was defined using operationalized level 1 MDS dementia criteria. These criteria required 1, a Montreal Cognitive Assessment (MoCA) score < 21; 2, cognitive deficits severe enough to impact daily living (MDSUPDRS sub-score I item 1, Cognitive impairment score ≥ 2 as criteria for ‘Dementia has impact on active daily living scale’); 3, impairment in at least two cognitive domains operationalized as impairment in two of the following four tasks: ≤ 2 of 3 points in the MoCA seven backwards test (attention); 0 points in the MoCA language fluency test item (language); ≤ 4 of 5 points in the word recall of the MoCA (delayed recall); ≤ 4 of 5 on the MoCA visuospatial/executive test. A Hamilton Depression Rating Scale (HDRS-17) < 24 was used as indicating the absence of severe depression. BannerHealth: The postmortem Clinical Dementia Rating Scale contains a set of questions from which a global summary rating, expressed on a scale of 0 to 3, is obtained. In general, subjects with a score of 0 are cognitively within normal limits for age, subjects with a score of 0.5 have cognitive impairment that does not meet criteria for dementia, subjects with a score of 1 have mild dementia, subjects with a score of 2 have moderate dementia and subjects with a score of 3 have severe dementia. On this dataset, this decision is made based on the last clinical assessment prior to death, if the last standardized assessment occurred less than 18 months prior to death. If the last assessment was done more than 18 months prior to death, then the decision is based on the postmortem diagnostic interview and/or on review of more recent private medical record. ParkWest: Dementia was defined using operationalized level 1 MDS dementia criteria. PIB: The Clinical Dementia Rating scale (CDR) was used to quantify the presence and severity of dementia. CDR 0 indicates no dementia, CDR 0.5 indicates cognitive decline (not meeting criteria for dementia), and CDR 1, 2, and 3 indicate mild, moderate, and severe dementia, respectively. DATATOP: Published criteria for disabling cognitive impairment were used (cognitive impairment leading to functional impairment). PreCEPT: PDD was defined as a score of 4 on the MDS-UPDRS subscale 1 item 1 defined as “cognitive dysfunction [that] precludes the patient’s ability to carry out normal activities and social interactions. PPMI: Dementia was extracted from PPMI database Cognitive_Categorization table, where Cognitive State score (COGSTATE) =3; Cognitive decline marked as ‘Yes’; Any 2 or more of the following cognitive tests are >1.5 SD below the standardized mean: 1,HVLT Total Recall ≤ 35; 2,HVLT Recognition Discrimination ≤ 35; 3,Benton Judgment of Line Orientation ≤ 6; 4,Letter Number Sequencing ≤ 6; 5,Semantic Fluency Test ≤35; 6,Symbol Digit Modalities ≤ 35; Functional impairment marked as ‘Yes’. | — | — | — | Combined discovery and replication dataset used to select and weight SNPs for PHS. Of the 3,821 individuals, 2,650 were part of the discovery dataset used to initially identify SNPs. |
|
PGS Performance Metric ID (PPM) |
PGS Sample Set ID (PSS) |
Performance Source | Trait |
PGS Effect Sizes (per SD change) |
Classification Metrics | Other Metrics | Covariates Included in the Model |
PGS Performance: Other Relevant Information |
|---|---|---|---|---|---|---|---|---|
| PPM002014 | PSS000997| Multi-ancestry (including European)| 404 individuals |
PGP000181 | Liu G et al. Nat Genet (2021) |
Reported Trait: Parkinson's disease dementia | HR: 2.05 [1.16, 3.61] | AUROC: 0.688 [0.519, 0.817] | Hazard's Ratio (HR, top 25% vs PHS of 0): 3.2 [1.26, 8.11] | Age at Parkinson's disease onset, sex, years of education, PCs(1-10), study cohort, genetic factors (genes: GBA, APOE ε4) | — |
|
PGS Sample Set ID (PSS) |
Phenotype Definitions and Methods | Participant Follow-up Time | Sample Numbers | Age of Study Participants | Sample Ancestry | Additional Ancestry Description | Cohort(s) | Additional Sample/Cohort Information |
|---|---|---|---|---|---|---|---|---|
| PSS000997 | All individuals had Parkinsons' disease. Dementia was defined by the following criteria for each cohort. DeNoPa: Dementia was defined using operationalized level 1 MDS dementia criteria. These criteria required 1, an MMSE< 26; 2, cognitive deficits severe enough to impact daily living (MDS-UPDRS sub-score I item 1, Cognitive impairment score ≥ 2 indicating ‘Dementia has impact on active daily living scale’); 3, impairment in at least two cognitive domains operationalized as impairment in two of the following four tasks: ≤ 3 of 5 points in the MMSE Seven backward test (attention); abnormal clock drawing test (executive dysfunction); subscore = 0 in the MMSE Pentagons (visuo-constructive ability); and ≤ 2 of 3 points in the 3-Word Recall of the MMSE (memory performance). A Geriatric Depression Scale-15 (GDS-15) score <10 was used to indicate the absence of severe depression. EPIPARK: Dementia was defined using operationalized level 1 MDS dementia criteria. These criteria required 1, a Montreal Cognitive Assessment (MoCA) score < 2127; 2, cognitive deficits severe enough to impact daily living (UPDRS sub-score I item 1, Intellectual impairment score ≥ 2 indicating ‘Dementia has impact on active daily living scale’); 3, impairment in at least two cognitive domains operationalized as impairment in two of the following four tasks: ≤ 2 of 3 points in the MoCA serial seven subtraction test; 0 points in the MoCA language fluency test item (language); ≤ 4 of 5 points in the word recall of the MoCA (delayed recall); ≤ 4 of 5 on the MoCA visuospatial/executive test. A Beck Depression Inventory (BDI) score ≤30 was used to indicate the absence of severe depression. HBS: Dementia was defined using operationalized level 1 MDS dementia criteria. These criteria required 1, an MMSE < 26; 2, cognitive deficits severe enough to impact daily living (UPDRS sub-score I item 1, Intellectual impairment score ≥ 2 indicating ‘Dementia has impact on active daily living scale’); 3, impairment in at least two cognitive domains operationalized as impairment in two of the following four tasks: ≤ 3 of 5 points in the MMSE Seven backward test (attention); abnormal clock drawing test (executive dysfunction); subscore = 0 in the MMSE Pentagons (visuo-constructive ability); and ≤ 2 of 3 points in the 3-Word Recall of the MMSE (memory performance). A Geriatric Depression Scale-15 (GDS-15) score <10 was used to indicate the absence of severe depression. | — | 404 individuals | — | European, NR | — | DeNoPa, EPIPARK, HBS | — |