UPTODATE Frontotemporal Dementia

7/21/2019 UPTODATE Frontotemporal Dementia

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UPTODATE Frontotemporal dementia: Clinical features and diagnosis

AuthorChristopher Randolph, PhD, ABPP-CNSection EditorSteven T DeKosky, MD, FAAN, FACPDeputy EditorApril F Eihler, MD, MP!

All topis are "pdated as ne# evidene $eo%es availa$le and o"r peer revie#proess is o%plete&

Literature reie! current through:'"n ()*+& This topic last updated:'"n (,()*.&

"#T$ODUCT"O# A#D #O%E#CLATU$E/ Frontote%poral de%entia 0FTD1 is ane"ropatholo2ially and linially hetero2eneo"s disorder harateri3ed $y 4oade2eneration o4 the 4rontal and5or te%poral lo$es 6*7& A2e o4 onset is typially in thelate 8)s or early 9)s, and the pri%ary initial linial %ani4estations are han2es in

personality and soial $ehavior or lan2"a2e, pro2ressin2 over ti%e to a %ore 2lo$alde%entia& A s"$set o4 patients %ay also e:hi$it sy%pto%s o4 e:trapyra%idal or %otorne"ron involve%ent at so%e point in the disease proess&

For %any years the linial syndro%e #as kno#n as Piks disease a4ter Arnold Pik,#ho ori2inally desri$ed the $ehavioral variant o4 this syndro%e in *;


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invaria$le1 presene o4 %ore e:tensive o2nitive de?its in these patients, oined theter% se%anti de%entia& >e #ill "se the ter%s pro2ressive non"ent aphasia andse%anti de%entia to desri$e these syndro%es, reo2ni3in2 that so%e patients %ay4all into an inter%ediate ate2ory&

This topi desri$es the linial 4eat"res and dia2nosis o4 4rontote%poral de%entiather de%entia syndro%es are desri$ed separately& The epide%iolo2y, patholo2y,patho2enesis, and treat%ent o4 4rontote%poral de%entia are also dis"ssedseparately& 0See Clinial %ani4estations and dia2nosis o4 Al3hei%er disease andEtiolo2y, linial %ani4estations, and dia2nosis o4 vas"lar de%entia and Clinia4eat"res and dia2nosis o4 de%entia #ith e#y $odies and Cholinesterase inhi$itorsin the treat%ent o4 de%entia and Treat%ent o4 $ehavioral sy%pto%s related tode%entia and Frontote%poral de%entia= Epide%iolo2y, patholo2y, andpatho2enesis and Frontote%poral de%entia= Treat%ent&1

CL"#"CAL FEATU$ES/ Frontote%poral de%entia 0FTD1 typially presents as either apro2ressive han2e in personality and soial $ehavior or as a pro2ressive 4or% o4aphasiaG in $oth ases ontin"in2 "lti%ately to a 2lo$al de%entia& @n a %inority o4patients, %otor sy%pto%s %ay 4ollo# the initial %ani4estation o4 the disorder& >hile adistintive linial syndro%e %ay $e identi?a$le in %ost patients as the diseaseevolves, in so%e series, liniians have noted that sy%pto%s overlap onsidera$lyand that so%e patients do not learly 4all into one ate2ory over another, parti"larlyin the early sta2es 6;7&

FTD appears to pro2ress %ore rapidly than Al3hei%er disease 6


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oss o4 soial a#areness& @ndivid"als #ith $vFTD %ay in4rin2e "pon soial nor%s in a%anner that is inon2r"ent #ith their pre%or$id $ehavior& Their sense o4 deor"%appears alteredG they %ay %ake oHensive re%arks and $ehave inappropriatelyPersonal hy2iene %ay $e aHeted& Patients %ay $e inontinent / voidin2 "rine or4ees in inappropriate plaes #itho"t apparent onern& They %ay o%%it antisoial,

even ri%inal ats& >hile inappropriate se:"al o%%ents are so%e#hat o%%on inpatients #ith $vFTD, hyperse:"al $ehavior is notG %ost patients #ith FTD havedi%inished li$ido&

Stereotyped or rit"al $ehaviors& These an inl"de insistin2 on the sa%e 4oods ore%ployin2 a repetitive ath-phrase& !oardin2, o"ntin2, and pain2 are a%on2 thedesri$ed $ehaviors&

Chan2e in eatin2 patterns& Patients #ith $vFTD 4re"ently overeat and %ay $in2e ordevelop 4ood 4ads& Alohol ons"%ption %ay $e e:essive& As the disease pro2resses,there %ay $e oral e:ploration o4 non4ood o$ets&

E%otional $l"ntin2 and loss o4 e%pathy& Patients %ay $e desri$ed as %ore sel4-entered, "nonerned a$o"t 4a%ily and 4riends, and old& They %ay have diI"ltyreo2ni3in2 e%otional e:pression in others 6.+7&

Mental ri2idity& Patients #ith $vFTD o4ten appear ine:i$le in their adherene toro"tines, as #ell as "na$le to adapt to ne# sit"ations and see anotherJs point o4 vie#&

De?its in %od"latin2 attention& This an %ani4est as distrati$ility andi%persistene, or as perseverative $ehavior& @n addition, so%e patients, *+ o4 *9patients in one series, de%onstrate "tili3ation $ehaviors 6.87& These are sti%"l"s-$o"nd ations in #hih the individ"al repeatedly "ses and re"ses o$ets #ithin theirsi2ht, despite irrelevane to sit"ation 0e2, they %i2ht repeatedly pik "p a o%$ in4ront o4 the% and "se it #hile partiipatin2 in a onversation1&

These $ehavioral han2es are pres"%ed to reet early involve%ent o4 or$ito4rontasyste%s 68,(*,((,.97& >hile so%eti%es re4erred to as 4rontal variant FTD, si2ni?ant

te%poral lo$e patholo2y is also evident in so%e o4 the $ehaviors, as #ell as onne"roi%a2in2 and ne"ropatholo2i e:a%ination o4 patients #ith $vFTD 68,*8,*97&Soially a$errant $ehavioral han2es have $een assoiated #ith 2reater involve%ento4 the ri2ht he%isphere 6(*,.,.;7& These $ehavior han2es are "se4"l indistin2"ishin2 FTD 4ro% other 4or%s o4 de2enerative de%entia 6(*,(8,.


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patients #ith $vFTD 6+(7& S"h patients %ay have nor%al %ini-%ental statee:a%ination sores& Even tests o4 e:e"tive 4"ntion %ay $e nor%al, sine s"ess onthese tests is lar2ely %ediated $y dorsolateral pre4rontal syste%s, #hih are relativelyspared in early $vFTD 68,(*,((,.9,+.-+87& As the disease pro2resses, ho#ever,ne"roo2nitive de?its e%er2e, parti"larly i%pair%ent o4 e:e"tive 4"ntions,

pro$le%-solvin2, "d2%ent, attention, or2ani3ation, and plannin2& @n ontrast, %e%oryand vis"al perept"al and spatial skills are $etter preserved, altho"2h rarely nor%a6*9,+),+9,+7&

A less o%%only-reo2ni3ed 4or% o4 $vFTD involves a pro2ressive diI"lty #ithor2ani3ational and e:e"tive skills, #ith $ehavioral han2es that are %ore s"$tle, atleast initially 6*;7& This is pres"%ed to reet 2reater early involve%ent o4 dorsolaterapre4rontal syste%s 0parti"larly on the le4t1, and an $e parti"larly diI"lt todia2nosis in the early sta2es&

Altered speeh patterns, #hile not as pro%inent as in the se%anti or non"entaphasia s"$types o4 FTD, are also present and an %ani4est either $y aspontaneityand pa"ity o4 speeh o"tp"t or as an inreased, o4ten press"red, speeh pattern 6+;7&ther a$nor%al lan2"a2e 4eat"res %ay inl"de stereotypy 0sin2le #ords or phrases"sed repeatedly1, eholalia, perseveration, and in late sta2es, %"tis%&

Frontal release si2ns %ay $e seen 02rasp, sno"t, and s"kin2 ree:es, inontinene1 ata so%e#hat earlier disease sta2e than is typial 4or patients #ith Al3hei%er disease&

Progressie aphasias/ Three distint 4or%s o4 pro2ressive aphasia are reo2ni3edGaltho"2h not all patients 4all learly into one ate2ory or another 6+


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te%poral variant o4 FTD& This "s"ally %ani4ests initially as a pro2ressive speehdist"r$ane #ith nor%al "eny, $"t i%paired o%prehension, ano%ia, and se%antiparaphasias 69,*+,*


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i%pair%ent d"rin2 the o"rse o4 their disease& S"h syndro%es inl"de=

%otor neuron disease/ Motor ne"ron disease 0MND1 %ay preede or 4ollo# thedevelop%ent o4 de%entia, #hih is "s"ally o4 the $vFTD type 69,)-+7& So%e st"diess"22est that as %any as 8) perent o4 patients #ith MND have or develop de%entiaGthe inidene o4 s"$se"ent MND in patients #ho present initially #ith FTD is lessertain& @n one st"dy o4 .9 onse"tively dia2nosed patients #ith FTD, ?ve hadde?nite MND, and t#o additional patients had a$nor%al eletro%yo2raphy that #asonsistent #ith MND 687& @n patients #ith MND and FTD, the %otor presentation is"s"ally that o4 pro2ressive %"s"lar atrophy #ith aidity and 4asi"lationsaHetin2 the $"l$ar %"sles and "pper e:tre%ities pri%arily& pper %otor ne"ronsi2ns %ay $e less pro%inent& @n patients #ho develop FTD-MND, linial 4eat"res o4$oth syndro%es are "s"ally apparent #ithin t#o years o4 initial presentationGpro2ression to death is %ore rapid in these patients& 0See JClinial 4eat"resJ a$ove&1

FTD-MND is dis"ssed separately& 0See Clinial 4eat"res o4 a%yotrophi lateraslerosis and other 4or%s o4 %otor ne"ron disease, setion on JCo2nitive sy%pto%sJand Fa%ilial a%yotrophi lateral slerosis, setion on JC


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involve%ent on ne"roi%a2in2& Not all o4 these have ne"ropatholo2i orrelation andthere4ore the relationship o4 these syndro%es to FTD is o4ten "nproven&

As an e:a%ple, one report desri$es () patients #ith ri2ht te%poral lo$e atrophy0si%ilar to the pattern desri$ed in the le4t te%poral lo$e in patients #ith se%antide%entia1 #ho had on presentation o%plaints o4 2ettin2 lost and %arkedprosopa2nosia alon2 #ith the %ore typial i%paired episodi %e%ory andharateristi $ehavioral dist"r$anes assoiated #ith $vFTD 6;+7&

D"FFE$E#T"AL D"A)#OS"S/ Any o4 the ne"rode2enerative de%entias %ay $eonsidered in the diHerential dia2nosis o4 FTD& Considered dia2noses #ill varyaordin2 to the linial syndro%e&

For $vFTD, psyhiatri disorders 0depression, o$sessive o%p"lsive disorder, $ipolardisorders1 are o%%only onsidered, as #ell as Al3hei%er disease 0AD1 and otherne"rode2enerative de%entias 6*


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de%entia #ith e#y $odies 6887&A ne"roi%a2in2 st"dy, "s"ally $rain %a2netiresonane i%a2in2 st"dy, is i%portant to e:l"de %ass lesions and other str"t"rapatholo2y in patients #ith pri%ary aphasia& 0See Approah to the patient #ithaphasia&1

D"A)#OS"S/ The dia2nosis o4 4rontote%poral de%entia 0FTD1 is %ade pri%arily $ylinial assess%ent& Ne"roi%a2in2 st"dies are re"ired to e:l"de alternativepatholo2ies and %ay provide s"pportin2 ?ndin2s& Ne"ropsyholo2ial testin2 an $ehelp4"l in patient %ana2e%ent $"t is not dia2nosti& ther la$oratory tests aretypially per4or%ed to e:l"de potentially reversi$le ontri$"tors or a"ses o4 theo2nitive i%pair%ent& 0See Eval"ation o4 o2nitive i%pair%ent and de%entia&1

Clinical assessment/ Consens"s linial riteria spei? to the three %aor linialsyndro%es 0ta$le * and ta$le ( and ta$le .1 #ere p"$lished in *


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MR@ %ay $e nor%al early in the o"rse o4 the disease 69,.(7& >ith linial pro2ressionthere is "s"ally evidene o4 4oal atrophy o4 the 4rontal and5or te%poral lo$es that#orsen over ti%e 6*)+7& Spei? patterns o4 atrophy have $een assoiated #ith thelinial syndro%e in a$o"t 8) to ) perent o4 patients 69,*;,8.,8+,9,9hile there %ay $e pre4erential involve%ent o4 ertain o2nitive do%ains in FTD thatare distint 4ro% AD and other 4or%s o4 ne"rode2enerative de%entia, eHorts to de?nene"ropsyholo2ial test $atteries and spei? pro?les o4 res"lts that relia$ly
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distin2"ish a%on2 disorders have not prod"ed onsistent res"lts 6((,+8,*((-*(97&Part o4 the hallen2e res"lts 4ro% the 4at that ne"ropsyholo2i test per4or%anevaries over the o"rse o4 the disease, and it is diI"lt to de?ne or ontrol 4or diseaseseverity $et#een diseases 6*(+7& Test ad%inistrators also need to $e sensitive to the4at that de?its in one do%ain 0e2, apathy, poor attention, i%paired o%prehension1

%ay lead to the appearane o4 de?its in another and sho"ld not rely on test soresalone 68+7&

Despite these li%itations, ertain patterns o4 ?ndin2s on ne"ropsyholo2ial testin2%ay s"pport the dia2nosis o4 FTD over AD& These inl"de a relatively #orseper4or%ane on tasks o4 4rontal e:e"tive 4"ntion and soial o2nition and relatively$etter per4or%ane on tests o4 %e%ory and vis"al spatial 4"ntion 6*


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!ere are the patient ed"ation artiles that are relevant to this topi& >e eno"ra2eyo" to print or e-%ail these topis to yo"r patients& 0Oo" an also loate patiented"ation artiles on a variety o4 s"$ets $y searhin2 on patient in4o and thekey#ord0s1 o4 interest&

SU%%A$* A#D $ECO%%E#DAT"O#S/ Frontote%poral de%entia 0FTD1 is ane"ropatholo2ially and linially hetero2eneo"s disorder harateri3ed $y 4oade2eneration o4 the 4rontal and5or te%poral lo$es&

Behavioral variant FTD 0$vFTD1 is the %ost o%%on linial s"$type& Patientspresent #ith pro2ressive han2e in $ehavior and personality& Feat"res an inl"dea$nor%al soial o%port%ent, "n"s"al eatin2 patterns, and rit"ali3ed $ehaviors,a%on2 others& Co2nitive i%pair%ents appear later and are %ost pro%inent in tasks o4e:e"tive 4"ntion, "d2%ent, and pro$le%-solvin2& 0See JBehavioral variantJ a$ove&1

Three aphasia syndro%es are reo2ni3ed=

Pro2ressive non"ent aphasia 0PNFA1 is a syndro%e harateri3ed $y inreasin2ano%ia, dys"eny, and a2ra%%atis% pro2ressin2 to %"tis%& 0See JPro2ressivenon"ent aphasiaJ a$ove&1

Se%anti de%entia 0SD1 patients have a "ent aphasia harateri3ed $y ano%ia,i%paired o%prehension, and se%anti paraphasi errors& Patients o4ten have a$roader loss o4 se%anti %e%ory that aHets vis"al perept"al skillsG episodi%e%ory is relatively spared& Behavioral 4eat"res o4ten develop in patients #ith SD&

0See JSe%anti de%entiaJ a$ove&1

o2openi phonolo2ial aphasia is harateri3ed $y an overall pa"ity and slo#nesso4 speeh o"tp"t #ith de?its in na%in2 and #ord retrieval, alon2 #ith phone%iparaphasias& 0See Jo2openi phonolo2ial aphasiaJ a$ove&1

Motor syndro%es assoiated #ith FTD inl"de pro2ressive s"pran"lear palsyortio$asal de2eneration, and FTD #ith %otor ne"ron disease& 0See JMotorsyndro%esJ a$ove&1

$vFTD %"st $e distin2"ished 4ro% other ne"rode2enerative de%entias, str"t"raldisease o4 the 4rontal lo$es, and psyhiatri disease& The diHerential dia2nosis o4 PNFAand SD inl"des slo#ly 2ro#in2 %ass lesions and atypial Al3hei%er disease 0AD1&0See JDiHerential dia2nosisJ a$ove&1


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The dia2nosis o4 FTD is %ade pri%arily on the $asis o4 linial 4eat"res& Ne"roi%a2in2st"dies 0"s"ally %a2neti resonane i%a2in21 are re"ired to r"le o"t other entitiesand %ay provide s"pportive evidene o4 FTD& 0See JDia2nosisJ a$ove&1

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UPTODATE Frontotemporal Dementia