A study published in the journal Neurology evaluates the brain degeneration or atrophy rates of presymptomatic carriers of mutations that can cause genetic FTD.

Determining the relative age at which brain atrophy in genetic forms of FTD begins to deviate from normal aging patterns is essential to find the best starting point for treatment, the study’s authors write. While past studies have examined atrophy rates, the authors note that their methodologies were often found to be unreliable in analyzing specific FTD-causing gene mutations. To better evaluate when atrophy rates begin to deviate, the authors undertook a “longitudinal study,” which involves collecting data on the same group of participants over the long term (often several years to a decade).

Fifty-six participants were recruited from the FTD Risk Cohort of the Erasmus University Medical Center in Rotterdam, Netherlands, between 2009 and 2019. The participants were all presymptomatic carriers of one of three main FTD-causing gene mutations: C9orf72, MAPT, and GRN. Over the course of a year or two, participants visited regularly with the researchers, with each visit consisting of a standard clinical assessment, a neurological examination, a neuropsychological assessment, and a brain MRI. During the study, some participants began to show symptoms of FTD.

The researchers used Quantib Neurodegenerative, an AI-powered radiology software tailored to study diseases like FTD, to analyze MRI scans. Data provided by Quantib ND was compared to data from a group of normal aging people. These people served as the reference and the group was comprised of a large sample of thousands of people without an FTD diagnosis.

While the study sought to determine when atrophy deviates from aging, the authors – led by Jackie Poos, PhD, a 2023 AFTD Holloway Postdoctoral Fellow — also provided insight into the differences between the atrophy patterns of the different FTD-causing gene mutations. Notably, the mutations affect different areas of the brain, including:

• The frontal lobes, which handle reasoning, social understanding, and executive functions like self-control and working memory.
• The parietal lobes, which help identify objects, determine spatial relationships, interpret pain and touch sensations, and understand spoken language.
• The occipital lobes, which process visual sensory information from the eyes.
• The temporal lobes, which help control speech and the ability to recognize/imitate rhythms, and have some involvement in short-term memory and scent recognition.
• The cerebellum, which controls the body’s vital functions like breathing and heartbeat, as well as helping to coordinate movement.

Overall, while the atrophy patterns of all carriers of FTD-causing gene mutations deviated from normal aging, each group was different in the way that their atrophy patterns progressed compared to control participants:

• GRN: A faster decline in the volume of the frontal, temporal, and parietal lobes was noticed from age 45 onwards, though all brain structures remained in the same range as normal aging between 45 and 70. More rapid decline in some brain regions, such as the occipital lobe and the cerebellum, occurred from age 60 onward.
• MAPT: Total brain volume showed the fastest decline by age 50; the authors note that at age 45, volume was still in the normal range. The temporal lobe seemed to decline the quickest starting at age 45, atrophying the fastest of all areas after 45. The parietal lobe declined less drastically but still faster than normal, and the occipital lobe and cerebellum remained within normal aging ranges.
• C9orf72: Total brain volume was the lowest of all groups by age 45 but showed minimal decline until age 60. Frontal lobe volume was the lowest at age 45. In contrast, the temporal and parietal lobes and cerebellum largely remained within normal aging between 45 and 70. The occipital lobe remained in the normal range entirely.

In addition to gathering a large amount of data on how particular atrophy patterns progress in genetic FTD and when, the study also confirmed previous findings that attributed the development of certain behaviors to specific atrophy patterns. For example, the study discovered that the more pronounced atrophy in the left temporal lobe compared to the right in persons with MAPT was associated with increased language difficulties, a finding identified in three previous studies cited by the authors.

An estimated 40% of FTD cases are familial (citation), reflecting a family history of dementia. A subset of familial FTD cases is genetic in nature, occurring when a parent passes a genetic variant associated with FTD to their child. Genetic testing can help families determine their genetic risk of FTD.

For those considering genetic testing, AFTD highly recommends meeting with a genetic counselor first. A genetic counselor can help families clarify their genetic risk and evaluate the potential risks and benefits of genetic testing.