Browsing by Author "Snitz, Beth E."

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    Genome-wide association study of brain amyloid deposition as measured by Pittsburgh Compound-B (PiB)-PET imaging
    (Springer Nature, 2018-10-25) Yan, Qi; Nho, Kwangsik; Del-Aguila, Jorge L.; Wang, Xingbin; Risacher, Shannon L.; Fan, Kang-Hsien; Snitz, Beth E.; Aizenstein, Howard J.; Mathis, Chester A.; Lopez, Oscar L.; Demirci, F. Yesim; Feingold, Eleanor; Klunk, William E.; Saykin, Andrew J.; Cruchaga, Carlos; Kamboh, M. Ilyas; Radiology and Imaging Sciences, School of Medicine
    Deposition of amyloid plaques in the brain is one of the two main pathological hallmarks of Alzheimer's disease (AD). Amyloid positron emission tomography (PET) is a neuroimaging tool that selectively detects in vivo amyloid deposition in the brain and is a reliable endophenotype for AD that complements cerebrospinal fluid biomarkers with regional information. We measured in vivo amyloid deposition in the brains of ~1000 subjects from three collaborative AD centers and ADNI using 11C-labeled Pittsburgh Compound-B (PiB)-PET imaging followed by meta-analysis of genome-wide association studies, first to our knowledge for PiB-PET, to identify novel genetic loci for this endophenotype. The APOE region showed the most significant association where several SNPs surpassed the genome-wide significant threshold, with APOE*4 being most significant (P-meta = 9.09E-30; β = 0.18). Interestingly, after conditioning on APOE*4, 14 SNPs remained significant at P < 0.05 in the APOE region that were not in linkage disequilibrium with APOE*4. Outside the APOE region, the meta-analysis revealed 15 non-APOE loci with P < 1E-05 on nine chromosomes, with two most significant SNPs on chromosomes 8 (P-meta = 4.87E-07) and 3 (P-meta = 9.69E-07). Functional analyses of these SNPs indicate their potential relevance with AD pathogenesis. Top 15 non-APOE SNPs along with APOE*4 explained 25-35% of the amyloid variance in different datasets, of which 14-17% was explained by APOE*4 alone. In conclusion, we have identified novel signals in APOE and non-APOE regions that affect amyloid deposition in the brain. Our data also highlights the presence of yet to be discovered variants that may be responsible for the unexplained genetic variance of amyloid deposition.
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    Implementation of Subjective Cognitive Decline criteria in research studies
    (Elsevier, 2017-03) Molinuevo, José L; Rabin, Laura A.; Amariglio, Rebecca; Buckley, Rachel; Dubois, Bruno; Ellis, Kathryn A.; Ewers, Michael; Hampel, Harald; Klöppel, Stefan; Rami, Lorena; Reisberg, Barry; Saykin, Andrew J.; Sikkes, Sietske; Smart, Colette M.; Snitz, Beth E.; Sperling, Reisa; van der Flier, Wiesje M.; Wagner, Michael; Jessen, Frank; Radiology and Imaging Sciences, School of Medicine
    INTRODUCTION Subjective Cognitive Decline (SCD) manifesting prior to clinical impairment could serve as a target population for early intervention trials in Alzheimer’s disease (AD). A working group, the Subjective Cognitive Decline Initiative (SCD-I), published SCD research criteria in the context of preclinical AD. To successfully apply them, a number of issues regarding assessment and implementation of SCD needed to be addressed. METHODS Members of the SCD-I met to identify and agree upon topics relevant to SCD criteria operationalization in research settings. Initial ideas and recommendations were discussed with other SCD-I working group members and modified accordingly. RESULTS Topics included SCD inclusion and exclusion criteria, together with the informant’s role in defining SCD presence and the impact of demographic factors. DISCUSSION Recommendations for the operationalization of SCD in differing research settings, with the aim of harmonization of SCD measurement across studies are proposed, to enhance comparability and generalizability across studies.
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    Linking Self-Perceived Cognitive Functioning Questionnaires Using Item Response Theory: The Subjective Cognitive Decline Initiative
    (American Psychological Association, 2023) Rabin, Laura A.; Sikkes, Sietske A. M.; Tommet, Douglas; Jones, Richard N.; Crane, Paul K.; Elbulok-Charcape, Milushka M.; Dubbelman, Mark A.; Koscik, Rebecca; Amariglio, Rebecca E.; Buckley, Rachel F.; Boada, Mercè; Chételat, Gaël; Dubois, Bruno; Ellis, Kathryn A.; Gifford, Katherine A.; Jefferson, Angela L.; Jessen, Frank; Johnson, Sterling; Katz, Mindy J.; Lipton, Richard B.; Luck, Tobias; Margioti, Eleni; Maruff, Paul; Molinuevo, Jose Luis; Perrotin, Audrey; Petersen, Ronald C.; Rami, Lorena; Reisberg, Barry; Rentz, Dorene M.; Riedel-Heller, Steffi G.; Risacher, Shannon L.; Rodriguez-Gomez, Octavio; Sachdev, Perminder S.; Saykin, Andrew J.; Scarmeas, Nikolaos; Smart, Colette; Snitz, Beth E.; Sperling, Reisa A.; Taler, Vanessa; van der Flier, Wiesje M.; van Harten, Argonde C.; Wagner, Michael; Wolfsgruber, Steffen; Alzheimer’s Disease Neuroimaging Initiative; Canadian Longitudinal Study on Aging; Health and Aging Brain Study; Health Disparities (HABS-HD) Study Team; Radiology and Imaging Sciences, School of Medicine
    Objective: Self-perceived cognitive functioning, considered highly relevant in the context of aging and dementia, is assessed in numerous ways-hindering the comparison of findings across studies and settings. Therefore, the present study aimed to link item-level self-report questionnaire data from international aging studies. Method: We harmonized secondary data from 24 studies and 40 different questionnaires with item response theory (IRT) techniques using a graded response model with a Bayesian estimator. We compared item information curves to identify items with high measurement precision at different levels of the self-perceived cognitive functioning latent trait. Data from 53,030 neuropsychologically intact older adults were included, from 13 English language and 11 non-English (or mixed) language studies. Results: We successfully linked all questionnaires and demonstrated that a single-factor structure was reasonable for the latent trait. Items that made the greatest contribution to measurement precision (i.e., "top items") assessed general and specific memory problems and aspects of executive functioning, attention, language, calculation, and visuospatial skills. These top items originated from distinct questionnaires and varied in format, range, time frames, response options, and whether they captured ability and/or change. Conclusions: This was the first study to calibrate self-perceived cognitive functioning data of geographically diverse older adults. The resulting item scores are on the same metric, facilitating joint or pooled analyses across international studies. Results may lead to the development of new self-perceived cognitive functioning questionnaires guided by psychometric properties, content, and other important features of items in our item bank.
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    Subjective Cognitive Decline in Older Adults: An Overview of Self-Report Measures Used Across 19 International Research Studies
    (IOS Press, 2015-09-24) Rabin, Laura A.; Smart, Colette M.; Crane, Paul K.; Amariglio, Rebecca E.; Berman, Lorin M.; Boada, Mercè; Buckley, Rachel F.; Chételat, Gaël; Dubois, Bruno; Ellis, Kathryn A.; Gifford, Katherine A.; Jefferson, Angela L.; Jessen, Frank; Katz, Mindy J.; Lipton, Richard B.; Luck, Tobias; Maruff, Paul; Mielke, Michelle M.; Molinuevo, José Luis; Naeem, Farnia; Perrotin, Audrey; Petersen, Ronald C.; Rami, Lorena; Reisberg, Barry; Rentz, Dorene M.; Riedel-Heller, Stefi G.; Risacher, Shannon L.; Rodriguez, Octavio; Sachdev, Perminder S.; Saykin, Andrew J.; Slavin, Melissa J.; Snitz, Beth E.; Sperling, Reisa A.; Tandetnik, Caroline; van der Flier, Wiesje M.; Wagner, Michael; Wolfsgruber, Steffen; Sikkes, Sietske A.M.; Department of Radiology and Imaging Sciences, IU School of Medicine
    Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844-852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures- approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcomes