Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint

Academic Article

Abstract

  • © 2019 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association. 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.
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    Author List

  • Staffaroni AM; Bajorek L; Casaletto KB; Cobigo Y; Goh SYM; Wolf A; Heuer HW; Elahi FM; Ljubenkov PA; Dever R
  • Start Page

  • 11
  • End Page

  • 21
  • Volume

  • 16
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  • 1