We will study the effects of frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), and mild cognitive impairment (MCI) on socioemotional functioning using laboratory procedures that allow for precise assessment of a number of aspects of actual emotional functioning including: (a) emotional reactivity (the type and magnitude of responses to salient challenges and opportunities), (b) emotion regulation (the ability to adjust emotional responses to situational demands) and (c) empathy and prosocial behavior (recognizing others'emotions and responding to their distress). These laboratory-based assessments measure the major aspects of emotional responding, including: (a) subjective emotional experience, (b) emotional expressive behavior, (c) emotional language, and (d) autonomic and somatic nervous system physiology. This approach allows us to identify specific areas of lost and preserved socioemotional functioning in FTLD and AD, compared to each other and to MCI and controls. A particular focus of the proposed work is on understanding the basis of symptoms of FTLD that are very troublesome for caregivers, including a progressive loss of """"""""warmth"""""""" and an increase in socially inappropropriate behavior. We will use our detailed analyses of emotional functioning to explore the particular deficits that contribute to these real world symptoms. Delineating specific deficits will enable us to make strong links to damage in specific brain circuits (explored via structural imaging) and particular kinds of neuropathology (explored at autopsy). In addition, we will determine the extent to which changes in particular aspects of socioemotional functioning are related to genetic risk factors for FTLD by studying unaffected family members with and without suspected genetic markers in families with a high incidence of FTLD.

Public Health Relevance

Frontotemporal lobar degeneration is a devastating neurological disease that primarily affects social and emotional functioning. Increasing our understanding of the specific nature of these effects and relating them to underlying biological factors will be useful for diagnosing this condition, for understanding the challenges and burdens presented to caregivers, and for evaluating the effectiveness of future treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG019724-13
Application #
8730069
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
13
Fiscal Year
2014
Total Cost
$152,352
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Ljubenkov, Peter A; Staffaroni, Adam M; Rojas, Julio C et al. (2018) Cerebrospinal fluid biomarkers predict frontotemporal dementia trajectory. Ann Clin Transl Neurol 5:1250-1263
La Joie, Renaud; Bejanin, Alexandre; Fagan, Anne M et al. (2018) Associations between [18F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample. Neurology 90:e282-e290
Kim, Eun-Joo; Brown, Jesse A; Deng, Jersey et al. (2018) Mixed TDP-43 proteinopathy and tauopathy in frontotemporal lobar degeneration: nine case series. J Neurol 265:2960-2971
Henry, Maya L; Hubbard, H Isabel; Grasso, Stephanie M et al. (2018) Retraining speech production and fluency in non-fluent/agrammatic primary progressive aphasia. Brain 141:1799-1814
Nana, Alissa L; Sidhu, Manu; Gaus, Stephanie E et al. (2018) Neurons selectively targeted in frontotemporal dementia reveal early stage TDP-43 pathobiology. Acta Neuropathol :
Vatsavayai, Sarat C; Nana, Alissa L; Yokoyama, Jennifer S et al. (2018) C9orf72-FTD/ALS pathogenesis: evidence from human neuropathological studies. Acta Neuropathol :
Ossenkoppele, Rik; Rabinovici, Gil D; Smith, Ruben et al. (2018) Discriminative Accuracy of [18F]flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders. JAMA 320:1151-1162
Mandelli, Maria Luisa; Welch, Ariane E; Vilaplana, Eduard et al. (2018) Altered topology of the functional speech production network in non-fluent/agrammatic variant of PPA. Cortex 108:252-264
Pressman, Peter S; Shdo, Suzanne; Simpson, Michaela et al. (2018) Neuroanatomy of Shared Conversational Laughter in Neurodegenerative Disease. Front Neurol 9:464
Caverzasi, Eduardo; Mandelli, Maria Luisa; Hoeft, Fumiko et al. (2018) Abnormal age-related cortical folding and neurite morphology in children with developmental dyslexia. Neuroimage Clin 18:814-821

Showing the most recent 10 out of 607 publications