This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Objectives: There is currently much interest in biomarkers of disease activity in frontotemporal lobar degeneration (FTLD). We assessed MRI and behavioral measures of progression in a longitudinal FTLD cohort.
Methods: Thirty-two patients with FTLD (11 behavioral variant frontotemporal dementia [bvFTD], 11 semantic dementia [SemD], 10 progressive nonfluent aphasia [PNFA]) and 24 age-matched healthy controls were assessed using volumetric brain MRI and standard behavioral measures (Mini-Mental State Examination, Frontal Assessment Battery, Clinical Dementia Rating Scale, Neuropsychiatric Inventory with Caregiver Distress scale) at baseline and 1 year later. A semi-automated image registration protocol was used to calculate annualized rates of brain atrophy (brain boundary shift integral [BBSI]) and ventricular expansion (ventricular boundary shift integral [VBSI]). Associations between these rates and changes in behavioral indices were investigated.
Results: Rates of whole brain atrophy were greater in the entire FTLD cohort and in each subgroup compared with controls (all p ≤ 0.004). Rates of ventricular expansion were greater in the entire cohort (p < 0.001) and the SemD (p = 0.002) and PNFA (p = 0.05) subgroups compared with controls. Changes in Mini-Mental State Examination, Frontal Assessment Battery, and Clinical Dementia Rating Scale scores were associated with MRI measures of progression, though not uniformly across FTLD subgroups. Both BBSI and VBSI yielded feasible sample size estimates for detecting meaningful treatment effects in SemD and PNFA language subgroups. Sample sizes were substantially larger using MRI biomarkers for the bvFTD subgroup, and using behavioral biomarkers in general.
Conclusions: Semi-automated MRI atrophy measures are potentially useful objective biomarkers of progression in frontotemporal lobar degeneration (FTLD); however, careful stratification of FTLD subtypes will be important in future clinical trials of disease-modifying therapies.
Glossary
- AD=
- Alzheimer disease;
- BBSI=
- brain boundary shift integral;
- bvFTD=
- behavioral variant frontotemporal dementia;
- CDR-SB=
- Clinical Dementia Rating Scale-Sums of Boxes;
- FTLD=
- frontotemporal lobar degeneration;
- SemD=
- semantic dementia;
- PNFA=
- progressive nonfluent aphasia;
- VBSI=
- ventricular boundary shift integral.
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Long-term Safety and Efficacy of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease
Dr. Marianne de Visser and Dr. Maudy Theunissen