Study identifies protective brain structure that delays the onset of frontotemporal dementia symptoms over 2 years

Source: Harp­er at al (2023)

Few peo­ple had prob­a­bly heard of fron­totem­po­ral demen­tia until ear­li­er this year, when the fam­i­ly of actor Bruce Willis announced the 68-year-old had been diag­nosed with the condition.

Fron­totem­po­ral demen­tia is a rare dis­ease – thought to account for only one in every 20 cas­es of demen­tia. Symp­toms usu­al­ly devel­op in a person’s late 50s, first affect­ing their behav­iour, per­son­al­i­ty and lan­guage abil­i­ty. Unlike oth­er forms of demen­tia, mem­o­ry only becomes impaired in the late stages of the disease.

Peo­ple diag­nosed with fron­totem­po­ral demen­tia usu­al­ly die with­in eight years of their diag­no­sis. While around 30% of cas­es are inher­it­ed, the cause of fron­totem­po­ral demen­tia is large­ly unknown. This also means there are no cures avail­able or treat­ments to slow its progression.

But recent research I have pub­lished with col­leagues at Lund Uni­ver­si­ty may have brought us one step clos­er in our under­stand­ing of how fron­totem­po­ral demen­tia devel­ops and pro­gress­es. We dis­cov­ered that the way your brain looks may deter­mine your resilience to the condition.

Brain folds

Dur­ing preg­nan­cy, as a foetus’s brain grows with­in the womb, it devel­ops its dis­tinc­tive folds while expand­ing with­in the skull. These brain folds play an impor­tant role in our lat­er cog­ni­tive function.

The folds that form ear­ly in foetal devel­op­ment are found in both sides of the brain in every per­son. But there’s one fold that some­times devel­ops lat­er on in the process. It’s called the paracin­gu­late sul­cus – and not every­one has it. In those that do have it, it can either be present on just one side of the brain or both sides.

The paracin­gu­late sul­cus is inter­est­ing, as its pres­ence can make a sig­nif­i­cant dif­fer­ence to cog­ni­tive abil­i­ty. For exam­ple, research has shown that peo­ple with a left but not a right paracin­gu­late sul­cus have a cog­ni­tive advan­tage – per­form­ing bet­ter on tasks involv­ing con­trol and even memory.

Giv­en the link between the paracin­gu­late sul­cus and cog­ni­tive func­tion, our research team at Lund Uni­ver­si­ty – along­side col­leagues in the US and Ams­ter­dam – began study­ing this brain fold’s role in dementia.

To real­ly under­stand what role the paracin­gu­late sul­cus plays, the team decid­ed to focus on a type of demen­tia where brain dam­age occurs in the same region as this brain fold. The obvi­ous choice for this research was fron­totem­po­ral demen­tia. This aggres­sive form of ear­ly-onset demen­tia pri­mar­i­ly attacks the frontal lobes of the brain – par­tic­u­lar­ly the cen­tral por­tions sur­round­ing the paracin­gu­late sulcus.

Our team stud­ied MRI brain images of 186 peo­ple who had been diag­nosed with fron­totem­po­ral demen­tia. We exclud­ed par­tic­i­pants who had fron­totem­po­ral demen­tia with a genet­ic cause. Around 57% of par­tic­i­pants had a paracin­gu­late sul­cus on the right side of their brain.

We dis­cov­ered that in par­tic­i­pants who had this extra fold on the right side of their brain, their demen­tia symp­toms began on aver­age two and a half years lat­er. This might mean that the paracin­gu­late sul­cus may delay the onset of symp­toms. These find­ings were sta­tis­ti­cal­ly sig­nif­i­cant – show­ing they weren’t due to chance or oth­er factors.

This two-and-a-half-year delay in symp­toms may not sound like much, but con­sid­er­ing the poor prog­no­sis of the con­di­tion and the bur­den of symp­toms, this is an extreme­ly mean­ing­ful amount of time for patients and their relatives.

Cognitive reserve

That said, after the symp­toms do begin, patients with this extra brain fold became sick­er at a faster rate and sur­vived for a short­er length of time than patients who do not have the fold. So despite the delay in symp­toms, patients with and with­out this extra brain fold still died at a sim­i­lar age.

Although it may sound strange that a fac­tor can both delay symp­toms and lat­er speed them up, this para­dox is a key fea­ture of a prin­ci­ple referred to in neu­ro­science as “brain reserve”. Brain reserve describes a struc­ture in the brain which pro­vides resilience to a dis­ease before symp­toms develop.

Crit­i­cal­ly, there becomes a point at which the dis­ease over­comes these pro­tec­tive mech­a­nisms, and the patient devel­ops symp­toms. After this crit­i­cal point, peo­ple with high brain reserve decline rapid­ly – faster than peo­ple with low brain reserve.

For exam­ple, high brain reserve explains why Alzheimer’s dis­ease starts lat­er in high­ly edu­cat­ed peo­ple – though the dis­ease pro­gress­es faster for them when symp­toms start. Accord­ing to our research, the paracin­gu­late sul­cus oper­ates by a sim­i­lar prin­ci­ple – first pro­tect­ing peo­ple from symp­toms, then pro­gress­ing rapid­ly when symp­toms do start.

Our research is the first to iden­ti­fy a pro­tec­tive struc­ture in the brain which delays the onset of symp­toms in peo­ple with fron­totem­po­ral demen­tia. If we can now uncov­er a way of pre­serv­ing this pro­tec­tive qual­i­ty, it could lead to the devel­op­ment of treat­ments which can help keep symp­toms – and the dis­ease – at bay.

– Luke Harp­er is a Neu­ro­science PhD stu­dent at Lund Uni­ver­si­ty, Swe­den. His research focus is on the iden­ti­fi­ca­tion of brain reserve fac­tors in fron­totem­po­ral demen­tia. He also works as a Con­sul­tant Neu­rol­o­gist at Malmö Uni­ver­si­ty Hos­pi­tal, Swe­den with a inter­est in Mul­ti­ple scle­ro­sis and asso­ci­at­ed dis­eases. This arti­cle was orig­i­nal­ly pub­lished on The Con­ver­sa­tion.

To Learn More:

• Deep learn­ing mod­el built on neu­roimag­ing data iden­ti­fies “Brain Age Gaps” as mark­ers of Alzheimer’s dis­ease (AD)
• Study: Build­ing cog­ni­tive reserve helps delay mem­o­ry and think­ing decline regard­less of genet­ic or child­hood markers