Study with 330 centenarians finds that cognitive decline is not inevitable

Hen­drik­je van Andel Schip­per (1890–2005)

Age-Relat­ed Cog­ni­tive Decline May Not Be Inevitable (Web­MD):

It is often assumed that a decrease in mem­o­ry and brain func­tion are inevitable parts of aging, but a new study of cen­te­nar­i­ans sug­gests otherwise.

Inves­ti­ga­tors found that despite the pres­ence of neu­ro­log­i­cal issues gen­er­al­ly asso­ci­at­ed with Alzheimer’s dis­ease (AD), many cen­te­nar­i­ans main­tained high lev­els of cog­ni­tive performance.

(Henne Hol­stege, PhD, assis­tant pro­fes­sor at Ams­ter­dam Uni­ver­si­ty Med­ical Cen­ter) said her inter­est in research­ing aging and cog­ni­tive health was inspired by the “fas­ci­nat­ing” sto­ry of Hen­drik­je van Andel Schip­per, who died at age 115 in 2005 “com­plete­ly cog­ni­tive­ly healthy.” Her moth­er, who died at age 100, was also cog­ni­tive­ly intact at the end of her life.

“I want­ed to know how it is pos­si­ble that some peo­ple can com­plete­ly escape all aspects of cog­ni­tive decline while reach­ing extreme ages,” Hol­stege said…

Despite find­ings of neu­ropatho­log­ic “hall­marks” of Alzheimer’s in the brains of the cen­te­nar­i­ans after their deaths, the mark­ers were not asso­ci­at­ed with cog­ni­tive per­for­mance or rate of decline … “Our find­ings sug­gest that after reach­ing age 100 years, cog­ni­tive per­for­mance remains rel­a­tive­ly sta­ble dur­ing ensu­ing years. There­fore, these cen­te­nar­i­ans might be resilient or resis­tant against dif­fer­ent risk fac­tors of cog­ni­tive decline,” the authors write. They also spec­u­late that resilience may be attrib­ut­able to greater cog­ni­tive reserve.

The Study:

Asso­ci­a­tion of Cog­ni­tive Func­tion Tra­jec­to­ries in Cen­te­nar­i­ans With Post­mortem Neu­ropathol­o­gy, Phys­i­cal Health, and Oth­er Risk Fac­tors for Cog­ni­tive Decline (JAMA Neurology):

• Ques­tion: Are cog­ni­tive­ly healthy cen­te­nar­i­ans resilient against fur­ther cog­ni­tive decline?
• Find­ings: In this cohort study of 330 self-report­ed cog­ni­tive­ly healthy cen­te­nar­i­ans, cog­ni­tive tra­jec­to­ries revealed only a slight decline in mem­o­ry func­tion­ing, while oth­er domains remained sta­ble over time. Cen­te­nar­i­ans main­tained high lev­els of cog­ni­tive per­for­mance despite being exposed to vary­ing lev­els of risk fac­tors of cog­ni­tive decline, includ­ing post­mortem Alzheimer disease–associated neuropathologies.
• Mean­ing: These find­ings indi­cate that pro­longed main­te­nance of cog­ni­tive func­tion­ing may be sup­port­ed by mech­a­nisms under­ly­ing resilience against risk fac­tors of cog­ni­tive decline.

Cog­ni­tive Tra­jec­to­ries and Resilience in Centenarians—Findings From the 100-Plus Study (accom­pa­ny­ing editorial):

• It is dif­fi­cult enough to recruit and enroll 330 cen­te­nar­i­ans, but to then have neu­ropatho­log­i­cal find­ings from 44 study par­tic­i­pants who had time­ly neu­ropsy­cho­log­i­cal assess­ments makes for a tru­ly unique study. It is also notable that the neu­ropsy­cho­log­i­cal assess­ments in the 100-plus Study were com­pre­hen­sive, which is not the case for oth­er stud­ies of extreme­ly old study par­tic­i­pants that may rely only on a Mini-Men­tal Sta­tus Exam­i­na­tion. Cog­ni­tive and brain resilience are defined respec­tive­ly by lev­el of cog­ni­tive func­tion and brain tis­sue struc­tur­al integri­ty in spite of a high degree of AD patho­log­i­cal bur­den. Rather than being resilient, indi­vid­u­als who live to age 100 years or more who do not have AD neu­ropatho­log­ic changes are con­sid­ered resis­tant to AD. By inte­grat­ing neu­ropsy­cho­log­i­cal assess­ments and neu­ropatho­log­i­cal stud­ies, sub­sets of cen­te­nar­i­an cog­ni­tive super­agers and off­spring who are either resis­tant or resilient to AD neu­ropatho­log­ic changes can be identified.

The Study in Context:

• Study: High Cog­ni­tive Reserve (CR) seen to sig­nif­i­cant­ly low­er demen­tia risk even in the pres­ence of high Alzheimer’s Dis­ease (AD) neuropathology