Testing Olfaction in Primary Care to Detect Alzheimer's Disease and Other Dementias (TOPAD)
The goal of TOPAD is to test the 12-item BSIT, a short, standardized version of the 40-item University of Pennsylvania Smell Identification Test (UPSIT), for detection of dementia among elderly persons with cognitive concerns in a community-based primary care setting.
Many elderly persons develop dementia that remains undiagnosed in primary care settings until it is severe, leading to catastrophic consequences for patients, families, and the health care system. Odor identification impairment with the 40-item UPSIT is a well-validated biomarker of dementia, particularly dementia of the Alzheimer’s type (DAT). The shorter version of the UPSIT, the 12-item BSIT, has been shown to be similar to the UPSIT in distinguishing and predicting MCI and DAT. We propose the BSIT for detection of dementia in primary care because it takes five minutes to administer, is inexpensive, and can be administered by non-medical personnel.
We are testing the BSIT for detection of dementia among 600 patients with cognitive concerns, without a diagnosis of dementia, age 65 years and older, who attend primary care practices in Northern Manhattan. The term “cognitive concerns” includes subjective cognitive decline (SCD), and warning signs identified by relatives, significant others, and health care providers. All participants will be tested with the BSIT, the MMSE, and other common dementia screening tools. The performance of tools will be assessed using as a gold standard cognitive diagnosis based using the 2011 National Institute on Aging (NIA)/Alzheimer Association (AA) recommendations for dementia and MCI using the National Alzheimer’s Coordinating Center (NACC) Unified Dataset (UDS) protocol.
Our primary outcome will be dementia diagnosis at the initial evaluation. Cognitive assessments will be repeated every 12 months. Our secondary outcomes will be cognitive transitions to dementia (and subtypes), MCI, and MCI subtypes.
Our primary aim is to compare the accuracy of the BSIT with the MMSE for dementia detection at initial evaluation among persons aged 65 years and older with cognitive concerns in primary care. In secondary analyses, we will examine the secondary outcomes and compare the accuracy of the BSIT for dementia detection with other instruments: Montreal Cognitive Assessment (MOCA), Mini-Cog, and Memory Impairment Screen (MIS).
Our secondary aim is to compare the BSIT with the MMSE in predicting cognitive transitions at 12 and 24 months. In secondary analyses, we will compare the BSIT with other screening instruments (MOCA, Mini-Cog, MIS). TOPAD will be conducted by a multidisciplinary team of experts in Alzheimer’s research, odor identification testing, dementia diagnosis, and primary care.
TOPAD is consistent with strategies 1C (“Accelerate Efforts to Identify Early and Presymptomatic Stages of Alzheimer's Disease”) and 2B (“Ensure Timely and Accurate Diagnosis”) of the 2015 Update of the National Plan to Address Alzheimer’s disease (NAPA).
We will create and maintain a biospecimen and data repository for discovery projects of blood-based biomarkers of dementia and DAT, including genomics, metabolomics, and proteomic approaches.
As of May 30, 2021, we completed recruitment of the sample of 600 participants including physician assessments and consensus diagnosis. We are finalizing the first analytic dataset and plan to submit publications on the analyses of the primary aim in the summer of 2021.
We are currently conducting follow-up assessments.
Available Data and Biospecimens for Data Sharing:
- Baseline consensus diagnosis (no cognitive impairment, cognitive impairment-not MCI, MCI, dementia) in 600 participants
- Baseline results of NACC-UDS cognitive battery in 600 participants
- Baseline results of the BSIT, MMSE-II
- APOE genotype in 509 participants
- Results of baseline blood tests including complete blood count, basic metabolic panel, HbA1c, Hepatic panel, B12, RPR, and TSH in 509 participants
- Frozen sera and plasma on 509 participants
Soliciting Data and Biospecimens for Ancillary Studies and Secondary Data Analysis:
Our process for data and resource sharing is to take solicitations for data and biospecimens following a modified NIH R03/R21 application format, including an aims page, and four pages of research strategy. This application will be reviewed by a committee comprised of PIs Luchsinger, Devanand, and co-investigators Teresi and Goldberg.
All applications scored 4 or better following the NIH scoring format will be approved. The committee will work with applicants to improve application as need to achieve this score.
Applications must not overlap with the stated primary and secondary aims of the original TOPAD grant application.