Here we outline the main findings from two recent FTD center publications. Learn more about our research in easy to digest terms!


Apathy in behavioral variant Frontotemporal Degeneration (bvFTD)

Adapted from “Apathy in Frontotemporal Degeneration: Neuroanatomical Evidence of Impaired Goal-directed Behavior”, Massimo et al., 2015

What we did know: Apathy is characterized by a general indifference or unresponsiveness. Importantly, it is a common feature of behavioral variant Frontotemporal Degeneration (bvFTD), with patients showing a diminished ability to develop or carry out goals (also known as goal directed behavior).

What we didn’t know: Previously, apathy was considered a single behavioral symptom. However, its occurrence in bvFTD can differ across patients and is not localized to one brain region. Instead, studies have shown that multiple brain regions can relate to apathetic symptoms, indicating that apathy might be a multi-component behavior. Specifically, the abilities to initiate, plan and become motivated  are thought to underlie goal directed behavior. If any one of these systems becomes compromised in bvFTD, Massimo and colleagues hypothesized that patients would show a decreased ability to develop and carry out goals, leading to increased apathy.

What this study shows: Massimo and colleagues tested the hypothesis that apathy in bvFTD is due to an impairment to one or more aspects of goal directed behavior: initiation, planning and/or motivation. They found that each behavior related to a partially distinct neuroanatomical region: poor initiation related to degeneration of the anterior cingulate, poor planning related to atrophy of the dorsolateral prefrontal cortex, and poor motivation related to atrophy of the orbitofrontal cortex.  The connecting white matter associated with these systems were also affected. These results show that apathy may be better understood as a behavior with multiple components that contribute to its occurrence in bvFTD.

What we can do in the future because of this study: This line of research can change the way that apathy is diagnosed and treated. A next step might be to more closely examine the differences between initiation, planning or motivation by outlining the different patterns of cognitive decline or disease spread.  Delineating the different brain regions that underlie apathetic behavior might help us better anticipate the disease course experienced by an individual.

Why should you care? Apathy is the most frequent symptom found in patients with bvFTD, with an estimated 86% of patients showing apathetic behaviors. A more detailed understanding of apathetic behavior in bvFTD can lead to more individualized care and a more effective treatment plan for a patient.

Learn more: While this study disentangles the multiple components of apathy, the researchers also found overlap between behaviors and regions of disease. To learn more, please visit: http://www.ncbi.nlm.nih.gov/pubmed/26617508


A chemical mechanism that protects against disease spread in FTD:  the role of hypermethylation

Adapted from “C9orf72 promoter hypermethylation is neuroprotective: Neuroimaging and neuropathologic evidence”, McMillan et al., 2015

What we did know: Genetic mutations can put an individual at risk for developing neurodegenerative disease. For example, mutations in the gene C9orf72 are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). Specifically, C9orf72 mutations lead to build-up of a protein called TDP-43, which can then cause brain cell death.

What we didn’t know: Studies examining the brain tissue of patients suggest an important role of hypermethylation in FTD. Hypermethylation is the addition of chemical compounds, known as methyl groups, to a gene. New evidence suggests that hypermethylation may protect against disease spread by blocking additional TDP-43 production from the C9orf72 gene. However, up to this point, there has been little longitudinal research demonstrating that C9orf72 hypermethylation is neuroprotective during a patient’s life and relates to their cognitive ability.

What this study shows: Researchers collected brain images and analyzed genetic data from blood samples from patients with C9orf72 mutations. Analyses revealed that patients with hypermethylation had less grey matter loss in the hippocampus, frontal cortex, and thalamus compared to patients without hypermethylation. Behavioral testing also revealed that patients with hypermethylation had better verbal memory recall. In a follow-up study, researchers examined brain cell loss at autopsy in patients who had C9orf72 mutations. Results again showed reduced brain cell loss in the presence of hypermethylation.

What we can do in the future because of this study: This study has exciting clinical implications. Drugs that can increase methylation levels or otherwise block the production of new TDP-43 protein may represent a new treatment to protect against neurodegeneration.

Why should you care: These cutting-edge findings may spur research into similar neuroprotective mechanisms and the role of hypermethylation in other neurodegenerative conditions.

Learn more: This paper also explores the interaction between hypermethylation status and rate of cognitive decline over time. To learn more, please visit: http://www.ncbi.nlm.nih.gov/pubmed/25795648

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