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  • 1
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    Sex differences in the genetic architecture of cognitive resilience to Alzheimer’s disease
    Oxford University Press (OUP) ; 2022
    In:  Brain Vol. 145, No. 7 ( 2022-07-29), p. 2541-2554
    Details
    In: Brain, Oxford University Press (OUP), Vol. 145, No. 7 ( 2022-07-29), p. 2541-2554
    Abstract: Approximately 30% of elderly adults are cognitively unimpaired at time of death despite the presence of Alzheimer’s disease neuropathology at autopsy. Studying individuals who are resilient to the cognitive consequences of Alzheimer’s disease neuropathology may uncover novel therapeutic targets to treat Alzheimer’s disease. It is well established that there are sex differences in response to Alzheimer’s disease pathology, and growing evidence suggests that genetic factors may contribute to these differences. Taken together, we sought to elucidate sex-specific genetic drivers of resilience. We extended our recent large scale genomic analysis of resilience in which we harmonized cognitive data across four cohorts of cognitive ageing, in vivo amyloid PET across two cohorts, and autopsy measures of amyloid neuritic plaque burden across two cohorts. These data were leveraged to build robust, continuous resilience phenotypes. With these phenotypes, we performed sex-stratified [n (males) = 2093, n (females) = 2931] and sex-interaction [n (both sexes) = 5024] genome-wide association studies (GWAS), gene and pathway-based tests, and genetic correlation analyses to clarify the variants, genes and molecular pathways that relate to resilience in a sex-specific manner. Estimated among cognitively normal individuals of both sexes, resilience was 20–25% heritable, and when estimated in either sex among cognitively normal individuals, resilience was 15–44% heritable. In our GWAS, we identified a female-specific locus on chromosome 10 [rs827389, β (females) = 0.08, P (females) = 5.76 × 10−09, β (males) = −0.01, P(males) = 0.70, β (interaction) = 0.09, P (interaction) = 1.01 × 10−04] in which the minor allele was associated with higher resilience scores among females. This locus is located within chromatin loops that interact with promoters of genes involved in RNA processing, including GATA3. Finally, our genetic correlation analyses revealed shared genetic architecture between resilience phenotypes and other complex traits, including a female-specific association with frontotemporal dementia and male-specific associations with heart rate variability traits. We also observed opposing associations between sexes for multiple sclerosis, such that more resilient females had a lower genetic susceptibility to multiple sclerosis, and more resilient males had a higher genetic susceptibility to multiple sclerosis. Overall, we identified sex differences in the genetic architecture of resilience, identified a female-specific resilience locus and highlighted numerous sex-specific molecular pathways that may underly resilience to Alzheimer’s disease pathology. This study illustrates the need to conduct sex-aware genomic analyses to identify novel targets that are unidentified in sex-agnostic models. Our findings support the theory that the most successful treatment for an individual with Alzheimer’s disease may be personalized based on their biological sex and genetic context.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awac177
    RVK:
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 2
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    Cognitively defined Alzheimer's dementia subgroups have distinct atrophy patterns
    Wiley ; 2023
    In:  Alzheimer's & Dementia
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    In: Alzheimer's & Dementia, Wiley
    Abstract: We sought to determine structural magnetic resonance imaging (MRI) characteristics across subgroups defined based on relative cognitive domain impairments using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and to compare cognitively defined to imaging‐defined subgroups. METHODS We used data from 584 people with Alzheimer's disease (AD) (461 amyloid positive, 123 unknown amyloid status) and 118 amyloid‐negative controls. We used voxel‐based morphometry to compare gray matter volume (GMV) for each group compared to controls and to AD‐Memory. RESULTS There was pronounced bilateral lower medial temporal lobe atrophy with relative cortical sparing for AD‐Memory, lower left hemisphere GMV for AD‐Language, anterior lower GMV for AD‐Executive, and posterior lower GMV for AD‐Visuospatial. Formal asymmetry comparisons showed substantially more asymmetry in the AD‐Language group than any other group ( p  = 1.15 × 10 −10 ). For overlap between imaging‐defined and cognitively defined subgroups, AD‐Memory matched up with an imaging‐defined limbic predominant group. DISCUSSION MRI findings differ across cognitively defined AD subgroups.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Article
    DOI: 10.1002/alz.13567
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2201940-6
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  • 3
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    Sex‐specific genetic predictors of memory, executive function, and language performance
    Wiley ; 2022
    In:  Alzheimer's & Dementia Vol. 18, No. S3 ( 2022-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 18, No. S3 ( 2022-12)
    Abstract: Alzheimer’s disease (AD) is more prevalent in women than men, and robust evidence shows sex differences in the biological response to the AD neuropathological cascade. However, there is a lack of large‐scale genetic studies on sex‐specific genetic predictors of AD‐related cognitive outcomes. Thus, we sought to elucidate the sex‐specific genetic etiology of memory, executive function, and language performance. Method This study included six cohorts of cognitive aging (N males =7,267, N females =9,518). We applied psychometric approaches to build harmonized memory, executive function, and language composite scores. Next, for all domains, we calculated slopes from the cognitive scores (two or more timepoints) with linear mixed effects models. Then we performed sex‐stratified and sex‐interaction GWAS on these phenotypes, covarying for baseline age and the first three genetic principal components. We meta‐analyzed across cohorts with a fixed‐effects model. Sensitivity analyses for all models restricted the sample to cognitively unimpaired individuals. Result In addition to well‐established associations with cognition at the APOE locus, we identified three genetic loci that showed sex‐specific effects with cognition. A chromosome 16 locus (rs114106271), a splicing‐quantitative trait locus for RP11‐152O14.4 and LINC02180 in the testis (GTEx), associated with baseline memory performance in men (β=0.13, P=2.40×10‐8; P Interaction =8.96×10‐6; Figures 1‐2) but not in women (β=‐0.01, P=0.76). A chromosome 14 locus (rs34074573), an expression‐quantitative trait locus (GTEx) for HOMEZ (a homeobox gene), and for BCL2L2 (a previously reported AD risk gene), associated with longitudinal memory performance in men (β=‐0.01, P=4.15×10‐8; P Interaction =5.83×10‐7; Figures 3‐4) but not in women (β=0.001, P=0.09). Finally, a chromosome 6 locus (rs9382966) associated with longitudinal language performance in men with near genome‐wide significance (β=‐0.004, P=6.29×10‐8; P Interaction =2.01×10‐4) but not in women (β=‐0.0003, P=0.61). Conclusion Our results highlight some key sex differences in the genetic architecture of cognitive outcomes. Findings further suggest that some sex‐specific genetic predictors have domain‐specific associations, providing an exciting opportunity to better understand the molecular basis of memory, executive function, and language through genomic analysis. Although our findings need to be replicated, our GWAS analyses highlight the contribution of sex‐specific genetic predictors beyond the APOE locus in conferring risk for late‐life cognitive decline.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v18.S3
    DOI: 10.1002/alz.067842
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 4
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    Synchronized sigmoidal mixed‐effects model for dynamics of cognitive decline relative to onset of Alzheimer’s disease in aging adults in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study.
    Wiley ; 2022
    In:  Alzheimer's & Dementia Vol. 18, No. S11 ( 2022-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 18, No. S11 ( 2022-12)
    Abstract: Modeling the dynamics of Alzheimer’s disease (AD) biomarkers over the entire continuum of AD progression is important, yet challenging due to limited resources to collect longitudinal biomarkers from the aging population with fully observed clinical spectrum of AD. This study proposed and applied a synchronized sigmoidal mixed‐effects model to characterize dynamics of longitudinal memory performance using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The model leveraged time to AD onset as the time scale and additionally allowed inclusion of participants without AD onset, drastically expanding future applications. Method ADNI participants with observed mild cognitive impairment (MCI) and/or AD onset ( n = 312, mean (SD) baseline age 74.9 (6.44) years) were included (Table 1). A memory composite previously built in ADNI was leveraged for all analyses. A synchronized sigmoidal mixed‐effects model was constructed for dynamics of memory performance with parameters for initial memory level, magnitude of decline, and half‐life of decline. For participants with observed MCI but not AD onset, an additional parameter ( t 0 ) quantifying the time from MCI onset to AD was incorporated (Figure 1). We considered random effects for all parameters and allowed t 0 to vary by age at MCI onset (nonlinearly), sex, apolipoprotein E ( APOE )‐ε4 status and their interactions. Result The mean initial harmonized memory score is 0.24 (95% CI: 0.17‐0.32). The mean decline in the harmonized memory score is 1.53 (95% CI: 1.43‐1.64). The mean time when the harmonized memory score declined by half is 0.57 years before AD onset (95% CI: 0.32‐0.82). Female is associated with faster progression from MCI onset to AD ( p = 0.002). Age at MCI onset is nonlinearly associated with MCI‐to‐AD progression ( p 〈 0.001) and APOE ‐ε4 status interacts with age at MCI onset on MCI‐to‐AD progression ( p = 0.002) (Figure 2). Conclusion The proposed synchronized sigmoidal mixed effect model can be used to characterize dynamics of AD biomarkers relative to AD onset using participants with and without AD onset. A model to estimate duration of MCI‐to‐AD progression can be simultaneously included for synchronization purpose, which identified gender, age at MCI onset and APOE ‐ε4 status as factors associated with MCI‐to‐AD progression.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v18.S11
    DOI: 10.1002/alz.063496
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 5
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    Associations of Sex, Race, and Apolipoprotein E Alleles With Multiple Domains of Cognition Among Older Adults
    American Medical Association (AMA) ; 2023
    In:  JAMA Neurology Vol. 80, No. 9 ( 2023-09-01), p. 929-
    Details
    In: JAMA Neurology, American Medical Association (AMA), Vol. 80, No. 9 ( 2023-09-01), p. 929-
    Abstract: Sex differences are established in associations between apolipoprotein E ( APOE ) ε4 and cognitive impairment in Alzheimer disease (AD). However, it is unclear whether sex-specific cognitive consequences of APOE are consistent across races and extend to the APOE ε2 allele. Objective To investigate whether sex and race modify APOE ε4 and ε2 associations with cognition. Design, Setting, and Participants This genetic association study included longitudinal cognitive data from 4 AD and cognitive aging cohorts. Participants were older than 60 years and self-identified as non-Hispanic White or non-Hispanic Black (hereafter, White and Black). Data were previously collected across multiple US locations from 1994 to 2018. Secondary analyses began December 2021 and ended September 2022. Main Outcomes and Measures Harmonized composite scores for memory, executive function, and language were generated using psychometric approaches. Linear regression assessed interactions between APOE ε4 or APOE ε2 and sex on baseline cognitive scores, while linear mixed-effect models assessed interactions on cognitive trajectories. The intersectional effect of race was modeled using an APOE  × sex × race interaction term, assessing whether APOE  × sex interactions differed by race. Models were adjusted for age at baseline and corrected for multiple comparisons. Results Of 32 427 participants who met inclusion criteria, there were 19 007 females (59%), 4453 Black individuals (14%), and 27 974 White individuals (86%); the mean (SD) age at baseline was 74 years (7.9). At baseline, 6048 individuals (19%) had AD, 4398 (14%) were APOE ε2 carriers, and 12 538 (38%) were APOE ε4 carriers. Participants missing APOE status were excluded (n = 9266). For APOE ε4, a robust sex interaction was observed on baseline memory (β = −0.071, SE = 0.014; P  = 9.6 × 10 −7 ), whereby the APOE ε4 negative effect was stronger in females compared with males and did not significantly differ among races. Contrastingly, despite the large sample size, no APOE ε2 × sex interactions on cognition were observed among all participants. When testing for intersectional effects of sex, APOE ε2, and race, an interaction was revealed on baseline executive function among individuals who were cognitively unimpaired (β = −0.165, SE = 0.066; P  = .01), whereby the APOE ε2 protective effect was female-specific among White individuals but male-specific among Black individuals. Conclusions and Relevance In this study, while race did not modify sex differences in APOE ε4, the APOE ε2 protective effect could vary by race and sex. Although female sex enhanced ε4-associated risk, there was no comparable sex difference in ε2, suggesting biological pathways underlying ε4-associated risk are distinct from ε2 and likely intersect with age-related changes in sex biology.
    Type of Medium: Online Resource
    ISSN: 2168-6149
    URL: Article
    DOI: 10.1001/jamaneurol.2023.2169
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 6
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    A genome-wide search for pleiotropy in more than 100,000 harmonized longitudinal cognitive domain scores
    Springer Science and Business Media LLC ; 2023
    In:  Molecular Neurodegeneration Vol. 18, No. 1 ( 2023-06-22)
    Details
    In: Molecular Neurodegeneration, Springer Science and Business Media LLC, Vol. 18, No. 1 ( 2023-06-22)
    Abstract: More than 75 common variant loci account for only a portion of the heritability for Alzheimer’s disease (AD). A more complete understanding of the genetic basis of AD can be deduced by exploring associations with AD-related endophenotypes. Methods We conducted genome-wide scans for cognitive domain performance using harmonized and co-calibrated scores derived by confirmatory factor analyses for executive function, language, and memory. We analyzed 103,796 longitudinal observations from 23,066 members of community-based (FHS, ACT, and ROSMAP) and clinic-based (ADRCs and ADNI) cohorts using generalized linear mixed models including terms for SNP, age, SNP × age interaction, sex, education, and five ancestry principal components. Significance was determined based on a joint test of the SNP’s main effect and interaction with age. Results across datasets were combined using inverse-variance meta-analysis. Genome-wide tests of pleiotropy for each domain pair as the outcome were performed using PLACO software. Results Individual domain and pleiotropy analyses revealed genome-wide significant (GWS) associations with five established loci for AD and AD-related disorders ( BIN1 , CR1 , GRN , MS4A6A , and APOE ) and eight novel loci. ULK2 was associated with executive function in the community-based cohorts (rs157405, P  = 2.19 × 10 –9 ). GWS associations for language were identified with CDK14 in the clinic-based cohorts (rs705353, P  = 1.73 × 10 –8 ) and LINC02712 in the total sample (rs145012974, P  = 3.66 × 10 –8 ). GRN (rs5848, P  = 4.21 × 10 –8 ) and PURG (rs117523305, P  = 1.73 × 10 –8 ) were associated with memory in the total and community-based cohorts, respectively. GWS pleiotropy was observed for language and memory with LOC107984373 (rs73005629, P  = 3.12 × 10 –8 ) in the clinic-based cohorts, and with NCALD (rs56162098, P  = 1.23 × 10 –9 ) and PTPRD (rs145989094, P  = 8.34 × 10 –9 ) in the community-based cohorts. GWS pleiotropy was also found for executive function and memory with OSGIN1 (rs12447050, P  = 4.09 × 10 –8 ) and PTPRD (rs145989094, P  = 3.85 × 10 –8 ) in the community-based cohorts. Functional studies have previously linked AD to ULK2 , NCALD , and PTPRD . Conclusion Our results provide some insight into biological pathways underlying processes leading to domain-specific cognitive impairment and AD, as well as a conduit toward a syndrome-specific precision medicine approach to AD. Increasing the number of participants with harmonized cognitive domain scores will enhance the discovery of additional genetic factors of cognitive decline leading to AD and related dementias.
    Type of Medium: Online Resource
    ISSN: 1750-1326
    URL: Article
    DOI: 10.1186/s13024-023-00633-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 7
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    Peripheral inflammatory biomarkers are associated with cognitive function and dementia: Framingham Heart Study Offspring cohort
    Wiley ; 2023
    In:  Aging Cell
    Details
    In: Aging Cell, Wiley
    Abstract: Inflammatory protein biomarkers induced by immune responses have been associated with cognitive decline and the pathogenesis of Alzheimer's disease (AD). Here, we investigate associations between a panel of inflammatory biomarkers and cognitive function and incident dementia outcomes in the well‐characterized Framingham Heart Study Offspring cohort. Participants aged ≥40 years and dementia‐free at Exam 7 who had a stored plasma sample were selected for profiling using the OLINK proteomics inflammation panel. Cross‐sectional associations of the biomarkers with cognitive domain scores ( N  = 708, 53% female, 22% apolipoprotein E ( APOE ) ε4 carriers, 15% APOE ε2 carriers, mean age 61) and incident all‐cause and AD dementia during up to 20 years of follow‐up were tested. APOE genotype‐stratified analyses were performed to explore effect modification. Higher levels of 12 and 3 proteins were associated with worse executive function and language domain factor scores, respectively. Several proteins were associated with more than one cognitive domain, including IL10, LIF‐R, TWEAK, CCL19, IL‐17C, MCP‐4, and TGF‐alpha. Stratified analyses suggested differential effects between APOE ε2 and ε4 carriers: most ε4 carrier associations were with executive function and memory domains, whereas most ε2 associations were with the visuospatial domain. Higher levels of TNFB and CDCP1 were associated with higher risks of incident all‐cause and AD dementia. Our study found that TWEAK concentration was associated both with cognitive function and risks for AD dementia. The association of these inflammatory biomarkers with cognitive function and incident dementia may contribute to the discovery of therapeutic interventions for the prevention and treatment of cognitive decline.
    Type of Medium: Online Resource
    ISSN: 1474-9718 , 1474-9726
    URL: Article
    DOI: 10.1111/acel.13955
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2099130-7
    SSG: 12
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  • 8
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    Measurement precision across cognitive domains in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data set.
    American Psychological Association (APA) ; 2023
    In:  Neuropsychology Vol. 37, No. 4 ( 2023-05), p. 373-382
    Details
    In: Neuropsychology, American Psychological Association (APA), Vol. 37, No. 4 ( 2023-05), p. 373-382
    Type of Medium: Online Resource
    ISSN: 1931-1559 , 0894-4105
    URL: Article
    DOI: 10.1037/neu0000901
    Language: English
    Publisher: American Psychological Association (APA)
    Publication Date: 2023
    detail.hit.zdb_id: 2102776-6
    SSG: 5,2
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  • 9
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    Longitudinal GWAS Identifies Novel Genetic Variants and Complex Traits Associated with Resilience to Alzheimer’s Disease
    Wiley ; 2022
    In:  Alzheimer's & Dementia Vol. 18, No. S4 ( 2022-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 18, No. S4 ( 2022-12)
    Abstract: We completed a large genetic analysis of resilience to cognitive decline in Alzheimer’s Disease (AD) and discovered novel variants, genes, and complex traits associated with better‐than or worse‐than‐expected cognitive performance given an individual’s age, sex, and APOE genotype. Method Leveraging 15,933 non‐Hispanic white participants across four longitudinal cohort studies of aging and AD (Figure 1), our group determined the effects of genetic variants on resilience metrics using mixed‐effects regressions. Models adjusted for age, sex, APOE ε4 allele count, presence of the APOE ε2 allele and all covariate interactions with interval (years from baseline). The outcomes of interest were residual cognitive resilience, quantified from residuals in three cognitive domains (memory, executive function, and language), and combined resilience, summarized as the covariance of educational attainment with residual cognitive resilience. Post‐GWAS analyses included gene tests using MAGMA and estimates of genetic correlation with 65 complex traits using GNOVA. Result We observed genome‐wide significant associations at multiple established AD loci, including BIN1 and CR1 (Figure 2). We observed a novel association with combined resilience on chromosome 13 (top SNP: rs11838654, MAF = 0.06, P = 4.7×10 −8 ; Figure 3) and a novel signal on chromosome 1 approaching significance (top SNP: rs2817183, MAF = 0.41, P = 5.1×10 −8 ). Interestingly, rs11838654 is an eQTL for four genes in hippocampus ( WBP4 , COG6 , MRPS31 , and NHLRC3I ; Braineac database). We also observed an association with residual cognitive resilience on chromosome 5 that approached genome‐wide significance (top SNP: rs4482935, MAF = 0.25, P = 5.5×10 −8 ; Figure 2). Gene‐level tests identified associations of CD2AP (P.fdr = 0.027) and ZNF146 (P.fdr = 0.049) with residual cognitive resilience and combined resilience, respectively. Additionally, we identified negative genetic correlations of combined resilience with ischemic stroke and coronary artery disease (all P.fdr 〈 2.5×10 −2 ; Figure 4). Conclusion Compared to models of resilience that regress out the effects of AD neuropathology on cognition, the present models benefit from larger sample size at the cost of molecular precision. Although the genetic architecture of resilience from these less precise models more closely resembles that of clinical AD, we uncovered novel genetic drivers of resilience through this approach. Such findings will require future replication but suggest a trajectory‐based definition of resilience holds substantial promise for discovery.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v18.S4
    DOI: 10.1002/alz.067816
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 10
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    Development of harmonized and co‐calibrated scores for memory, executive functioning, language, and visuospatial in the AIBL Study, ADNI, and NACC datasets
    Wiley ; 2022
    In:  Alzheimer's & Dementia Vol. 18, No. S11 ( 2022-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 18, No. S11 ( 2022-12)
    Abstract: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study is a prospective study collecting extensive cognitive, clinical, fluid, and imaging biomarkers data from older adults living in Australia. Integration of outcomes between large prospective studies of AD will provide greater precision in models of AD brain‐behavior relationships, so it is important to align composite scores for cognitive domains between such studies. Methods Detailed methods for AIBL, the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the National Alzheimer’s Coordinating Center (NACC) have been published. Briefly, AIBL participants had cognition assessed with an extensive neuropsychological test battery alongside health and biomarker assessments at entry and each 18‐months thereafter. Granular‐level cognitive data were obtained and an expert panel of two neuropsychologists and a behavioral neurologist categorized each element as assessing memory, executive functioning, language, visuospatial, or none of these, exactly as we have done previously. We also identified elements we had previously calibrated from other studies; after careful quality control and confirmation these served as anchors enabling co‐calibration. We used confirmatory factor analysis bi‐factor models to calibrate the AIBL battery with other studies. We used those calibrations to obtain co‐calibrated scores for all AIBL participants at every study visit. Here we show descriptive statistics for baseline visits, separately by diagnosis (normal cognition, mild cognitive impairment (MCI), dementia) for two enrollment waves for AIBL as well as for each phase of ADNI and across the Uniform Data Set (UDS) 1 & 2 (UDS1/2) and UDS3 time periods for NACC. Results Box plots for memory, executive functioning, language, and visuospatial for people with normal cognition are in Figure 1, MCI in Figure 2 , and dementia in Figure 3 . These figures show there is substantial cognitive variation across waves within these disease stage groups and across studies. Conclusion Co‐calibrated neuropsychological domain scores provide a common metric for integrating cognitive data across studies. Co‐calibrated scores aggregated across large prospective AD studies such as AIBL, ADNI, and NACC provide a foundation for large‐scale models of the development of AD and can serve as phenotypes for genetics studies. Co‐calibrated scores are available from AIBL, ADNI, and from NACC.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v18.S11
    DOI: 10.1002/alz.064534
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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