Debate: Are depression and dementia two sides of the same coin? And, if they are, how to best approach treatment?

Every sev­en sec­onds, some­one in the world is diag­nosed with demen­tia. A typ­i­cal case that I often see in my prac­tice is as fol­lows: A 76-year-old woman has a two-year his­to­ry of pro­gres­sive wors­en­ing of short-term mem­o­ry and cog­ni­tive decline. She can’t recall the names of her grand­chil­dren and is dev­as­tat­ed by her dete­ri­o­rat­ing abilities.

How­ev­er, this is not the first time in her life that she has had feel­ings of loss and despair. Over the past 30 years, she has inter­mit­tent­ly strug­gled with depres­sion and anx­i­ety. Her fam­i­ly has many ques­tions: Does she have demen­tia or Alzheimer’s? Could her depres­sion have led to a demen­tia diag­no­sis? Is it only depres­sion and not demen­tia? These are all good ques­tions and the col­lec­tive answer to them is “yes.”

Dementia and depression

Demen­tia and depres­sion are the two dread­ed “D” diag­noses that are increas­ing­ly rob­bing our aging pop­u­la­tion of health and hap­pi­ness as both dis­or­ders approach near epi­dem­ic pro­por­tions, exac­er­bat­ed by the COVID-19 pan­dem­ic. In fact, the preva­lence of depres­sion in peo­ple with demen­tia has been report­ed to exceed 60 per cent.

Despite their obvi­ous dif­fer­ences, it is becom­ing ever more appar­ent that depres­sion and demen­tia may be two sides of the same coin. Peo­ple with demen­tia often have depres­sion; if the depres­sion remains untreat­ed, the asso­ci­at­ed mem­o­ry and cog­ni­tive prob­lems wors­en. Con­verse­ly, a sig­nif­i­cant his­to­ry of depres­sion seems to be a risk fac­tor for demen­tia; the two dis­or­ders may thus co-exist in a vicious self-sus­tain­ing cycle.

In the age of COVID-19, these con­nec­tions become even more stark — and high­light an even more dire sce­nario. If lone­li­ness and iso­la­tion are already not­ed risk fac­tors for both depres­sion and demen­tia, then the lock­downs pre­vent­ing fam­i­ly and care­givers from inter­act­ing with their loved ones in long-term care served to has­ten the decline. We are only just begin­ning to observe the grim con­se­quences of this imposed iso­la­tion — a nec­es­sary step, tak­en with the goal of sav­ing lives, but which, in the end, may cause even more destruction/despair in the lives of those liv­ing with demen­tia and Alzheimer’s.

Complex connection

Clear­ly, the con­nec­tion between demen­tia and depres­sion is deep, mul­ti-faceted and a grow­ing area of sci­en­tif­ic and pub­lic health interest.

More than half of patients with demen­tia also suf­fer from depres­sion. In the ear­ly stages of demen­tia, the afflict­ed indi­vid­ual real­izes that they are not the same per­son they once were — cog­ni­tion is slowed, mem­o­ry is not as sharp, words don’t queue up in the brain as fast as they used to. This serves to fur­ther com­pro­mise cog­ni­tive reserve and to allow the symp­toms of demen­tia to be man­i­fest­ed ear­li­er and with greater sever­i­ty. To fur­ther com­pli­cate the rela­tion­ship, many peo­ple with demen­tia may not be able to rec­og­nize that they are, in fact, depressed.

As well, it appears that peo­ple with a past his­to­ry of depres­sion have dou­ble the risk of devel­op­ing demen­tia. This is true even if the depres­sion occurred more than a decade before the onset of dementia.

There are clear mech­a­nisms for this increased risk. Pro­longed dam­age to a part of the brain called the hip­pocam­pus, a find­ing linked to depres­sion, has been pro­posed to under­lie this causative rela­tion­ship. This is fur­ther con­firmed by stud­ies that demon­strate increased hip­pocam­pal deposits of plaques and tan­gles in peo­ple with Alzheimer’s (the patho­log­i­cal hall­marks of the dis­ease) with life­time his­to­ries of depres­sion. In addi­tion, oth­er researchers spec­u­late that brain inflam­ma­tion that often occurs when a per­son is depressed may be a long-term trig­ger­ing fac­tor for demen­tia. These expla­na­tions fur­ther demon­strate the soci­etal need to rec­og­nize and treat depression.

Progression of a single disease?

In some peo­ple, depres­sion and demen­tia are not cause-and-effect, but may be sim­ply dif­fer­ent stages of the same sin­gle-dis­ease process.

Depres­sion is not only a risk fac­tor for demen­tia, it may also be the start of the demen­tia. Depres­sion may be the ear­ly man­i­fes­ta­tion of an under­ly­ing neu­rode­gen­er­a­tive disease.

For such peo­ple, the treat­ment of depres­sion would be of par­tic­u­lar impor­tance. How­ev­er, in oth­er peo­ple, the treat­ment for depres­sion may para­dox­i­cal­ly wors­en the symp­toms of demen­tia. Cog­ni­tive impair­ment in depressed elder­ly can be exac­er­bat­ed by the use of anti­de­pres­sants, though with the use of mod­ern SSRI-type anti­de­pres­sants, this should become less likely.

Overlapping symptoms

Final­ly, the symp­toms of demen­tia and depres­sion can mim­ic each oth­er, which means peo­ple with demen­tia may be mis­tak­en­ly diag­nosed with depres­sion and vice ver­sa. Ear­ly demen­tia symp­toms include mem­o­ry prob­lems (par­tic­u­lar­ly remem­ber­ing recent events), increas­ing con­fu­sion, behav­iour changes, apa­thy, social with­draw­al and inabil­i­ty to do every­day tasks.

Many of these symp­toms are shared with depres­sion, in which patients expe­ri­ence sleep dis­tur­bances, lack of ener­gy (so even small tasks take extra effort), anx­i­ety, rest­less­ness and prob­lems with think­ing, con­cen­trat­ing, mak­ing deci­sions and remem­ber­ing things.

Obvi­ous­ly, the rela­tion­ship between demen­tia and depres­sion is com­plex, with the two dis­or­ders being eas­i­ly con­fused with each oth­er as well as being risk fac­tors for each oth­er. Both are dev­as­tat­ing, both are increas­ing in preva­lence in our aging pop­u­la­tion and both may be sig­nif­i­cant­ly affect­ed by the stress­es of COVID-19.

How­ev­er, there is one major dif­fer­ence sep­a­rat­ing the two: there are no effec­tive ther­a­pies for demen­tia, where­as there are a num­ber of poten­tial­ly effec­tive agents for depres­sion. Efforts should always be made to detect the pres­ence of depres­sion, and if present, to treat it, there­by elim­i­nat­ing one of the faces of this two-faced demen­tia-depres­sion coin.

Dr. Don­ald Weaver is Pro­fes­sor of Chem­istry and Direc­tor of Krem­bil Research Insti­tute at the Uni­ver­si­ty of Toron­to. This arti­cle was orig­i­nal­ly pub­lished on The Con­ver­sa­tion.

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