Memory Performance in Asymptomatic and Prodromal Familial Frontotemporal Lobar Degeneration: Findings from the ALLFTD Consortium
Bradley Boeve1, Julie Fields1, Jeremy Syrjanen1, Walter Kremers1, Adam Staffaroni2, Edward Huey3, Katya Rascovsky4, Marisa Ramos5, Leah Forsberg1, Hilary Heuer2, Adam Boxer2, Howard Rosen2
1Mayo Clinic, 2UCSF, 3Columbia University, 4University of Pennsylvania, 5UCLA
Objective:
To assess performance on memory measures among asymptomatic and minimally symptomatic members of familial frontotemporal lobar degeneration (f-FTLD) kindreds.
Background:
Memory impairment is generally considered an exclusionary criterion for the diagnosis of overt behavioral variant frontotemporal dementia (bvFTD).
Design/Methods:
We analyzed performance across 7 measures in the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD,
www.allftd.org) Consortium protocol that assess memory functioning. The measures include the National Alzheimer’s Coordinating Center Uniform Data Set Version 3 – Craft Story Immediate Recall (CSImm) and Delayed Recall (CSDel), Benson Figure Delayed Recall (BenDel), and the California Verbal Learning Test – Learning (CVLearn), Immediate Recall (CVImm), Delayed Recall (CVDel), and Recognition (CVRecog). Testing was performed in asymptomatic [defined by global FTLD Clinical Dementia Rating (CDR) score of 0] non-mutation (AsymM-) and mutation (AsymM+) carriers and minimally symptomatic (defined by FTLD CDR=0.5) mutation carriers (SymM+) in kindreds with f-FTLD. Performance was considered abnormal (Abnl) for z-scores ≤-1.5.
Results:
Data from 255 AsymM- (mean age 47±13 years, 38% male), 181 AsymM+ (mean age 43±14 years, 45% male), and 36 SymM+ (mean age 56±12 years, 39% male) participants were analyzed. The frequencies of Abnl between AsymM- and AsymM+ for ≥2 tests (23.9% vs 26.4%), ≥4 tests (5.3% vs 7.5%) and ≥6 tests (0.4% vs 0.6%) were not different (p>0.05). The frequencies of Abnl between AsymM+ and SymM+ for ≥2 tests (26.4% vs 44.1%, p=0.038), ≥4 tests (7.5% vs 20.6%, p=0.018) and ≥6 tests (0.6% vs 8.8%, p=0.001) were significantly different. The frequencies of Abnl in the SymM+ group per memory measure were: CSImm 23.5%, CSDel 29.4%, BenDel 20%, CVLearn 22.9%, CVImm 26.5%, CVDel 29.4%, and CVRecog 29.4%.
Conclusions:
Among mutation carriers with prodromal bvFTD clinical features, a significant minority have impairment on memory measures. The presence of memory impairment should not preclude a diagnosis of prodromal bvFTD.