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

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.

Utility of the global CDR plus NACC FTLD rating and development of scoring rules: Data from the ARTFL/LEFFTDS Consortium.

Introduction: We created global rating scoring rules for the CDR plus NACC FTLD to detect and track early frontotemporal lobar degeneration (FTLD) and to conduct clinical trials in FTLD.

Methods: The CDR plus NACC FTLD rating was applied to 970 sporadic and familial participants from the baseline visit of Advancing Research and Treatment in Frontotemporal Lobar Degeneration (ARTFL)/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS). Each of the eight domains of the CDR plus NACC FTLD was equally weighed in determining the global score.

Nonlinear Z-score modeling for improved detection of cognitive abnormality.

Introduction: Conventional Z-scores are generated by subtracting the mean and dividing by the standard deviation. More recent methods linearly correct for age, sex, and education, so that these "adjusted" Z-scores better represent whether an individual's cognitive performance is abnormal. Extreme negative Z-scores for individuals relative to this normative distribution are considered indicative of cognitive deficiency.

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

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.

Individualized atrophy scores predict dementia onset in familial frontotemporal lobar degeneration.

Introduction: Some models of therapy for neurodegenerative diseases envision starting treatment before symptoms develop. Demonstrating that such treatments are effective requires accurate knowledge of when symptoms would have started without treatment. Familial frontotemporal lobar degeneration offers a unique opportunity to develop predictors of symptom onset.

Selective Patterns of Cognitive Impairment in Spinocerebellar Ataxia Type 6 and Idiopathic Late-Onset Cerebellar Ataxia.

Purpose: To determine cognitive impairment patterns in patients with spinocerebellar ataxia type 6 (SCA6) compared to patients with idiopathic late-onset cerebellar ataxia (ILOCA).

Methods: Neurocognitive testing was conducted on 21 SCA6, nine ILOCA, and 27 controls subjects. Intergroup differences were assessed using the Wilcoxon signed-ranked test or Student's t-test.

Resting-state functional connectivity and cognitive dysfunction correlations in spinocerebelellar ataxia type 6 (SCA6).

Objective: The aim of this study is to evaluate the correlation between resting state functional MRI (RS-fMRI) activity and motor and cognitive impairment in spinocerebellar ataxia type 6 (SCA6).

Methods: Twelve patients with genetically confirmed SCA6 and 14 age matched healthy controls were imaged with RS-fMRI. Whole brain gray matter was automatically parcellated into 1000 regions of interest (ROIs).

Structural cerebellar correlates of cognitive and motor dysfunctions in cerebellar degeneration.

See King et al. (doi:10.1093/aww348) for a scientific commentary on this article.