Familial Dementia Neuroimaging Lab

Overview

The Familial Dementia Neuroimaging Lab, led by Yakeel Quiroz, PhD, is focused on the study of cognitive and brain changes that may predispose individuals to develop dementia later in life. Understanding the pathophysiology of neurodegeneration and identifying preclinical biomarkers for early diagnosis of dementia, especially as measured by neuropsychology and neuroimaging, are fundamental goals for the lab.

Our research uses a variety multimodal neuroimaging types, including PET, sMRI, fMRI, DTI, and integrates genetic, molecular and neuropsychological data to characterize some of the earliest changes associated with dementia.

We recently received funding from the National Institute of Health Office of the Director and the National Institute of Aging to investigate memory network dysfunction as an early marker of preclinical Alzheimer’s disease (AD). For this study, we are comparing a Colombian kindred with early-onset AD with a group of asymptomatic older individuals who are participants in the Harvard Aging Brain Study at Massachusetts General Hospital and are considered at high risk through molecular pathology imaging to develop late onset sporadic AD.

Research Projects

Our lab is currently focused on two areas of research:

Preclinical markers of Alzheimer’s disease

The overall goal of this project is to study the impact of amyloid and tau pathology on memory function in preclinical stages of Alzheimer’s disease (AD) and their role in subsequent neuronal death and cognitive decline.

This project leverages our access to two extraordinarily rich preclinical AD groups:

1. The Colombian kindred with Presenilin 1 E280A mutation
2. A group of asymptomatic older individuals who are participants in the Harvard Aging Brain Study (HABS) at Mass General and are considered at high risk (by molecular pathology imaging) to develop late-onset sporadic AD

The primary goals of this research are to:

• Investigate abnormalities of associative-memory processes as a possible cognitive marker of preclinical AD
• Investigate brain hyper-activity/hyper- connectivity as a marker of early AD pathology
• Examine the role of tau and amyloid aggregation in memory network dysfunction

Neuroimaging markers for the differential diagnosis of young-onset dementias

This project examines the role of white matter disease and genetic and molecular factors on subtle cognitive decline in preclinical early-onset Alzheimer’s disease, frontotemporal dementia and CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy).

Current Collaborations

Our current projects involve collaborations with investigators at numerous institutions:

• Harvard Aging Brain Study
• Massachusetts General Hospital General Psychology Assessment Center
• Mass General Multicultural Neuropsychology Program (MUNDOS)
• Multicultural Alzheimer's Prevention Program (MAPP)
• Schepens Eye Research Institute, Massachusetts Eye and Ear
• Alzheimer’s Prevention Initiative (Phoenix, AZ)
• Banner Alzheimer’s Institute (Phoenix, AZ)
• Hospital Pablo Tobon Uribe (Colombia)
• Neuroscience Group of the University of Antioquia (Colombia)

Current Grant Support

• NIH Director's Early Independence Award Program
• ECOR Claflin Distinguished Scholar Award
• Mass General Physician-Scientist Development Award

Publications

Full PubMed publications list.

Quiroz YT, Schultz A, Chen K, Protas H, Brickhouse M, Fleisher AS, Langbaum JB, Thiyyagura P, Fagan AM, Shah AR, Muniz M, Arboleda-Velasquez JF, Munoz C, Garcia G, Acosta-Baena N, Giraldo M, Tirado V, Ramirez D, Tariot PN, Dickerson BC, Sperling RA, Lopera F, Reiman EM. Brain imaging and blood biomarker abnormalities in children with autosomal-dominant Alzheimer's disease: A cross-sectional study. JAMA Neurol 2015 Aug 1; 72(8):912-919. doi: 10.1001/jamaneurol.2015.1099.

Aguirre-Acevedo DC, Lopera F, Henao E, Tirado V, Muñoz C, Giraldo M, Bangdiwala SI, Reiman EM, Tariot PN, Langbaum JB, Quiroz YT, Jaimes F. Cognitive Decline in a Colombian Kindred With Autosomal Dominant Alzheimer Disease: A Retrospective Cohort Study. JAMA Neurol. 2016 Apr;73(4):431-8. doi: 10.1001/jamaneurol.2015.4851.

Primo V, Graham M, Bigger-Allen AA, Chick JM, Ospina C, Quiroz YT, Manent J, Gygi SP, Lopera F, D'Amore PA, Arboleda-Velasquez JF. Blood biomarkers in a mouse model of CADASIL. Brain Res. 2016 Aug 1; 1644:118-26. doi: 10.1016/j.brainres.2016.05.008.

Mormino EC, Papp KV, Rentz DM, Donohue MC, Amariglio R, Quiroz YT, Chhatwal J, Marshall GA, Donovan N, Jackson J, Gatchel JR, Hanseeuw BJ, Schultz AP, Aisen PS, Johnson KA, Sperling RA.Early and late change on the preclinical Alzheimer's cognitive composite in clinically normal older individuals with elevated β-amyloid. Alzheimers Dement. 2017 Feb 27; pii: S1552-5260(17)30044-4. doi: 10.1016/j.jalz.2017.01.018.