Neurology: Inherited frontotemporal dementia, how does long-term cognitive function change?

Frontotemporal dementia (FTD) is a common cause of dementia, often presenting at a young age and having a devastating impact on daily lif.

Figure 1: Paper cover image

Studies of hereditary FTD have shown that disease pathology occurs years before symptoms appea.

To date, most studies investigating cognitive decline in asymptomatic inherited FTD have small sample sizes, limited annual follow-up, and/or have not included all three major causes of inherited FT.

Larger, international cohort studies with longer follow-up are essential to identify cognitive markers that mark disease onset at the earliest stages and can measure changes in disease progressio.

Hereby, Jackie .

Figure 2: The results of the paper

Carriers of C9orf72, GRN, and MAPT pathogenic variants and controls underwent annual neuropsychological assessments covering eight cognitive domains as part of the Genetic FTD Initiative (GENFI), a prospective multicenter cohort researc.

They included 207 C9orf72, 206 GRN, 86 MAPT pathogenic variant carriers, and 255 control.

The cognitive characteristics of carriers of MAPT pathogenic variants are poor memory at CDR plus NACC FTLD 0, a decline in language ability over time from CDR plus NACC FTLD 5 stage, and rapid executive dysfunction at CDR plus NACC FTLD ≥ 1.

GRN pathogenic variant carriers had a decline in verbal fluency and visual construction at CDR plus NACC FTLD 5 stage, and other cognitive domains began to decline gradually at CDR plus NACC FTLD ≥1.

The significance of the study lies in its findings: Cognitive decline occurs during the asymptomatic and prodromal stages of inherited FT.

This confirms the value of neuropsychological assessments in tracking clinical onset and progression, and can inform clinical trials, select sensitive endpoints to measure treatment effects, and determine the optimal time window to initiate treatmen.

Original source:Poos JM, MacDougall A, van den Berg E, et a.