Discoveries about the genetic bases of frontotemporal lobar dementia (FTLD) have provided researchers with an unprecedented ability to characterize the pre-symptomatic stages of this disease. This capability is critical to ascertaining the earliest clinical features of the disease and identifying biomarkers that can be used for early diagnosis and in treatment studies. The proposed project will examine individuals from a single family with a genetic mutation for FTLD who are approaching the age of disease onset, offering a unique and highly controlled environment in which to identify the earliest clinical features and biomarkers of this devastating disease. Specifically, this study proposes to follow the offspring generation of a large family with a known mutation in the MAPT (tau) gene to determine the earliest clinical features of FTLD and the variables which may modify disease onset and course. At least 90 members of the offspring generation of a single family will be offered participation in a longitudinal study examining cognition, behavior, psychiatric symptoms, and lifestyle features. Moreover, this proposal includes the use of state of the art neuroimaging tools including both structural and functional modalities, gray and white matter quantification, and regional and network analyses to detect the earliest signs of disease. Individuals will undergo genetic testing to determine carrier status, will be comprehensively characterized at baseline, and will be followed annually over the course of the study to examine change in clinical and imaging variables over time as a function of carrier status. Additionally, the proposed study will carefully characterize lifetime physical activity and alcohol and recreational drug use to determine if these lifestyle variables are early manifestations of disease and / or modify disease onset and course. Finally, biological specimens including cerebrospinal fluid and blood plasma will be longitudinally collected in an effort to characterize changes in brain protein levels that may provide early information regarding the onset and course of disease.

Public Health Relevance

Improved characterization of FTLD at its earliest stages is a necessary step in facilitating earlier disease detection and developing disease modifying therapeutics that can be applied in advance of irrevocable neuropathological changes.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Sutherland, Margaret L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Columbia University (N.Y.)
Schools of Medicine
New York
United States
Zip Code
Cheran, Gayathri; Wu, Liwen; Lee, Seonjoo et al. (2018) Cognitive Indicators of Preclinical Behavioral Variant Frontotemporal Dementia in MAPT Carriers. J Int Neuropsychol Soc :1-11
Cheran, Gayathri; Silverman, Hannah; Manoochehri, Masood et al. (2018) Psychiatric symptoms in preclinical behavioural-variant frontotemporal dementia in MAPT mutation carriers. J Neurol Neurosurg Psychiatry 89:449-455
Huey, Edward D; Cosentino, Stephanie; Chapman, Silvia et al. (2018) Self-report depressive symptoms are dissociated from tremor severity in essential tremor. Parkinsonism Relat Disord 50:87-93
Pottier, Cyril; Zhou, Xiaolai; Perkerson 3rd, Ralph B et al. (2018) Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study. Lancet Neurol 17:548-558
Bertrand, Elodie; Azar, Martina; Rizvi, Batool et al. (2018) Cortical thickness and metacognition in cognitively diverse older adults. Neuropsychology 32:700-710
Fieo, Robert A; Silverman, Hannah; O'Shea, Deirdre et al. (2018) Establishing dimensionality of sexual behaviours in patients with regional brain dysfunction. Brain Inj 32:1455-1464
Huey, Edward D; Lee, Seonjoo; Cheran, Gayathri et al. (2017) Brain Regions Involved in Arousal and Reward Processing are Associated with Apathy in Alzheimer's Disease and Frontotemporal Dementia. J Alzheimers Dis 55:551-558
Devanand, Davangere P; Pelton, Gregory H; D'Antonio, Kristina et al. (2017) Low-dose Lithium Treatment for Agitation and Psychosis in Alzheimer Disease and Frontotemporal Dementia: A Case Series. Alzheimer Dis Assoc Disord 31:73-75
Louis, Elan D; Cosentino, Stephanie; Huey, Edward D (2016) Depressive symptoms can amplify embarrassment in essential tremor. J Clin Mov Disord 3:11
Huey, Edward D; Lee, Seonjoo; Lieberman, Jeffrey A et al. (2016) Brain Regions Associated With Internalizing and Externalizing Psychiatric Symptoms in Patients With Penetrating Traumatic Brain Injury. J Neuropsychiatry Clin Neurosci 28:104-11

Showing the most recent 10 out of 30 publications