Course Title: Plenary G - Age-related Trajectory of Brain Changes and Cognitive Decline in Autosomal Dominant Alzheimer’s Disease (Quiroz)
Credit Hours: 1
Instructor(s) Yakeel T. Quiroz
Age-related Trajectory of Brain Changes and Cognitive Decline in Autosomal Dominant Alzheimer’s Disease
Abstract & Learning Objectives:
We work with an extraordinary extended family of approximately 6,000 individuals in Antioquia, Colombia, which contains roughly 1,200 carriers of an autosomal-dominant mutation (PSEN1 E280A). These carriers are expected to develop early onset Alzheimer’s Disease, with almost 100% certainty, and have a well-characterized disease course, with mild cognitive impairment (MCI) occurring at a median age of 44, and dementia at a median age of 49. For the past two decades, we have been studying these families to identify some of the earliest brain changes that are associated with their predisposition to develop Alzheimer’s dementia later in life. Our work with these families has provided evidence of abnormalities in brain structure and function, several years before clinical onset. We have also shown that young adults who carry this PSEN1 mutation have brain amyloidosis, as measured by PET imaging, at the age of 28, an average of 16 years before their estimated age of clinical onset and have elevated levels of tau pathology in their late 30s, an average of 6 years before symptom onset. Most recently, we started to study carriers from these Colombian families who remained cognitively unimpaired until older ages. We reported on the first case who developed MCI three decades after the estimated age of clinical onset. This patient was found to also have two copies of the APOE3 Christchurch mutation, suggesting for the first time that this genetic variant may be protective against AD dementia. This extraordinary case has offered a truly unique opportunity to understand resistance to Alzheimer’s disease, and is opening completely new avenues for Alzheimer’s research and treatment.
Upon conclusion of this course, learners will be able to:
- Describe the trajectory of Alzheimer’s disease (AD) biomarkers in preclinical autosomal dominant AD
- Explain the relationships between markers of brain pathology and cognitive decline in preclinical AD
- Discuss advantages and disadvantages of studying biomarkers in familial forms of AD
Dr. Yakeel T. Quiroz is Associate Professor in the Departments of Psychiatry and Neurology at Harvard Medical School and Massachusetts General Hospital (MGH) in Boston, MA. She is the Director of the MGH Familial Dementia Neuroimaging Lab and the Multicultural Alzheimer’s Prevention Program-MAPP. She earned her master’s degree in cognitive neuroscience and PhD in clinical psychology from Boston University. She completed a postdoctoral fellowship in neuropsychology and brain imaging of Alzheimer’s disease (AD) at MGH. Her research interests include brain imaging, genomics, early detection and preclinical biomarkers of Alzheimer’s disease and other dementias.
She is the principal investigator of the Colombia-Boston (COLBOS) longitudinal biomarker study on autosomal-dominant Alzheimer’s disease, which follows individuals from the world’s largest extended family with a single, AD-causing mutation (E280A in Presenilin1). Dr. Quiroz’s research has focused on characterizing biological and physiological changes that may predispose individuals to develop memory loss or dementia later in life. Her work has already provided evidence of brain abnormalities in cognitively-intact individuals at high risk for AD, decades before their clinical onset. Her findings have helped the field to re-conceptualize Alzheimer as a sequence of changes that begins decades before cognitive decline, and which may be targeted by promising disease-slowing treatments at a time in which they might have their most profound effect. Her research work has resulted in several publications that have generated considerable discussion in the field and has achieved recognition by colleagues at the national and international level. Dr. Quiroz’s work has been recognized with several awards, including an NIH Director’s Early Independence Award, the FABBS Foundation Early Career Impact Award, the MGH Research Scholar Award, and the Alzheimer’s Association Grundke-Iqbal Award for Alzheimer’s Research.