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Alzheimers Dement. 2019 Nov 26. pii: S1552-5260(19)35366-X. doi: 10.1016/j.jalz.2019.08.196. [Epub ahead of print]

Clinical and volumetric changes with increasing functional impairment in familial frontotemporal lobar degeneration.

Author information

1
Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
2
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
3
Department of Neurology, Case Western Reserve University, Cleveland, OH, USA.
4
Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
5
Tau Consortium, Rainwater Charitable Foundation, Fort Worth, TX, USA.
6
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
7
Department of Neurology, University of Washington, Seattle, WA, USA.
8
Department of Neurology, Frontotemporal Disorders Unit, Massachusetts General Hospital, Harvard Medical School, Boston MA, USA.
9
Association for Frontotemporal Degeneration, Radnor, PA, USA.
10
National Centralized Repository for Alzheimer's Disease and Related Disorders (NCRAD), Indiana University, Indianapolis, IN, USA.
11
Department of Neurology, University of North Carolina, Chapel Hill, NC, USA.
12
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
13
Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
14
Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
15
Department of Psychiatry, Washington University, St. Louis, MO, USA; Department of Neurology, Washington University, St. Louis, MO, USA.
16
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA; Department of Neurology, Columbia University, New York, NY, USA.
17
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
18
Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
19
Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
20
Department of Neurology and Neurotherapeutics, Center for Alzheimer's and Neurodegenerative Diseases, The University of Texas, Southwestern Medical Center at Dallas, Dallas, TX, USA; Department of Internal Medicine, The University of Texas, Southwestern Medical Center at Dallas, Dallas, TX, USA.
21
National Alzheimer Coordinating Center (NACC), University of Washington, Seattle, WA, USA.
22
Department of Neurosciences, Parkinson and Other Movement Disorders Center, University of California, San Diego, San Diego, CA, USA.
23
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
24
Department of Neurology, Alzheimer's Disease Center, University of Alabama at Birmingham, Birmingham, AL, USA.
25
Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
26
The Bluefield Project, San Francisco, CA, USA.
27
Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
28
Laboratory of Neuroimaging (LONI), University of Southern California, Los Angeles, CA, USA.
29
Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA. Electronic address: Howie.rosen@ucsf.edu.

Abstract

INTRODUCTION:

The Advancing Research and Treatment in Frontotemporal Lobar Degeneration and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects longitudinal studies were designed to describe the natural history of familial-frontotemporal lobar degeneration due to autosomal dominant mutations.

METHODS:

We examined cognitive performance, behavioral ratings, and brain volumes from the first time point in 320 MAPT, GRN, and C9orf72 family members, including 102 non-mutation carriers, 103 asymptomatic carriers, 43 mildly/questionably symptomatic carriers, and 72 carriers with dementia.

RESULTS:

Asymptomatic carriers showed similar scores on all clinical measures compared with noncarriers but reduced frontal and temporal volumes. Those with mild/questionable impairment showed decreased verbal recall, fluency, and Trail Making Test performance and impaired mood and self-monitoring. Dementia was associated with impairment in all measures. All MAPT carriers with dementia showed temporal atrophy, but otherwise, there was no single cognitive test or brain region that was abnormal in all subjects.

DISCUSSION:

Imaging changes appear to precede clinical changes in familial-frontotemporal lobar degeneration, but specific early clinical and imaging changes vary across individuals.

KEYWORDS:

C9ORF72; Familial; Frontotemporal lobar degeneration; GRN; Genetic; MAPT

PMID:
31784375
DOI:
10.1016/j.jalz.2019.08.196
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