Abstract
Introduction: Identifying clinical measures that track disease in the earliest stages of frontotemporal lobar degeneration (FTLD) is important for clinical trials. Familial FTLD provides a unique paradigm to study early FTLD. Executive dysfunction is a clinically relevant hallmark of FTLD and may be a marker of disease progression. Methods: Ninety-three mutation carriers with no symptoms or minimal/questionable symptoms (MAPT, n = 31; GRN, n = 28; C9orf72, n = 34; Clinical Dementia Rating scale plus NACC FTLD Module < 1) and 78 noncarriers enrolled through Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects studies completed the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH-EXAMINER) and the UDS neuropsychological battery. Linear mixed-effects models were used to identify group differences in cognition at baseline and longitudinally. We examined associations between cognition, clinical functioning, and magnetic resonance imaging volumes. Results: NIH-EXAMINER scores detected baseline and differences in slopes between carriers and noncarriers, even in carriers with a baseline Clinical Dementia Rating scale plus NACC FTLD Module = 0. NIH-EXAMINER declines were associated with worsening clinical symptoms and brain volume loss. Discussion: The NIH-EXAMINER is sensitive to cognitive changes in presymptomatic familial FTLD and is a promising surrogate endpoint.
Original language | English (US) |
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Pages (from-to) | 11-21 |
Number of pages | 11 |
Journal | Alzheimer's and Dementia |
Volume | 16 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2020 |
Keywords
- Behavioral variant
- Cognition
- Corticobasal syndrome
- Fluency
- Genetic
- Inhibition
- Neuropsychology
- Nonfluent variant
- Primary progressive aphasia
- Progranulin
- Progressive supranuclear palsy
- Semantic variant
- Set-shifting
- Tau
- Working memory
ASJC Scopus subject areas
- Clinical Neurology
- Geriatrics and Gerontology
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Health Policy
- Developmental Neuroscience
- Epidemiology