NGHIEN Cl/U M 6 | LIEN QUAN G I O A MOT S 6 TRIEU CHi>NG LAM S A N G VOI K H O A N G C A C H LIEN MOC VA TH& TICH H A I M A TREN PHIM C O N G H U - ^ N G T O
SO NAO 6 B E N H N H A N ALZHEIMER
Nguydn Giang Hoa^, Nguydn Duy Blc^ Nguyin Minh Hai^\
Trdn Hal Anh'. Nguydn Van Chuvng^ Hisao Nishijo'
*Ldp cao hgc 18, 'Hoc w6n QuSn y, Vi^t Nam 'Dai hgc Toyama, Nh$t Ban
Nghien cdu tien ciru tren 38 b$nh nhan sa sOt tri tug do bdnh Alzheimer dwgc chin doin trin lim sdng theo tieu chuin DSM-IV vd NINCDS-ADFiDA tCr thdng 10 nam 2010 din thing 4 ndm 2011 tgi Dan w nghien ciru tri nhd vd sa sOt tri tu$ thu0c khoa Tim thin kinh - vlin Lio khoa Trung wang. Cdc b$nh nhdn dwgc khdm Idm sing, idm cdc brae nghi$m thin kinh tdm f^
vi chgp MRI sg ndo, phdn logi sa sut tri fud ti^eo thang diim CDR. Kit qua nghiin cuv cho thiy s6 b$nh nhin /^zheimer c6 r6l logn tri nhd ngan hgn li 59,7%, roi togn tri nhd toin bi Id 42,1 %, thit ngdn: 92,1%. va thit dgng: 57.9%. S6 b$nh nhdn cd diim CDR = 11d 10.5%. CDR = 2:
52,6%, vd CDR = 3: 36,8%. Nhdm binh nhin mOc dO n^ng (CDR = 3) cho thiy thi tich viing hdi mi c6s^ twang quan thu$n vdi rii logn tri nhd ngSn hgn va tri nhd todn bd (rs iin lUQt li 0,82 vi 0.59). Khoing cdch IHn mdc d cdc binh nhin Alzheimer cd s(r twang quan vdi rii hgn tri nhd ngin hgn (r =-0.S3)vi rti togn tri nhd todn b^(r=Q.32).
TO idida: B$nh Alzheimer, khoing cich Iiin mdc. thi tich hii mi
I.DATVAND^
Bdnh Alzheimer, mdt cdn t>dnh thodi hda khdng phgc hdi cua hd thin kinh, gdy thodi hda nghidm trgng mdt s i viing ndo cd lidn quan chgt die vdi tri nhd vd cdm xue. Cdc vCing thudng duac thiy cd tiiay doi dgi thi trdn ndo cOa cdc t)dnh nhdn Al^eimer Id vCing hdi md. vd ndo khdu, hgnh nhdn. vd mdt s6 vung cua vd bdn clu dgi nao (dgc bigt Id vCing vd ndo lidn hop cua thiiy trdn vd thiiy thdi duang), hgeh nin (basa) ganglia), nhdn xanh (nudeus eoemleus) vd nhdn dudng dan (nudeus raphd) [1], [2], [3].
Viing hdi md cd diirc ndng quan trgng trong hgc tdp vd trf nhd, dgc bigt Id chde ndng chuyin tri nhd ngln hgn thdnh tri nhd ddi hgn duac luu gid. Do vdy khi cd tin thuang vung hdi md (trang nhdng chirng bgnh ttiodi hda thin kinh, nhu bdnh Alzheimer) thi faf nhd, tu duy vd nhdn Uidc tq dnh hudng [2], [3]. Trong nghi^ cdu ndy chdng tdi khao sdt mdt sd dgc
dilm lan sdng, c ^ Idm sdng d bdnh nhdn Alzheimer vd ddnh gid mdi tuang quan gida thi tich hdi ma vd khoang cdch lidn mdc vdi mdt s i tridu chdng Idm sdng vd dilm bIc nghidm thin kinh tdm ly d nhdm bdnh nhdn Alzheimer.
2. Ddi Tl/ONG VA PHU'aNG PHAP NGHIDN CI>U
2.1. Ddi tti*gmg nghidn cdu
38 bdnh nhdn dug'c chin dodn trdn Idm sdng Id t)dnh Alzheimer theo tidu chuln DSM- IV vd NINCDS-ADRDA, trong thdi gian td thdng 10/2010 din 4/2011, tgi Dan vj nghidn edu tri nhd vd sa siit tri tud, thudc khoa Tdm thin kinh - Vidn Ldo khoa Tmng uang 2.2. Phiramg phdp nghien cdu
- Khdm thin kinh vd Idm trie nghidm thin kinh tdm h^ theo bdnh dn nghidn a>u.
- Chin dodn bdnh Alzheimer fa-dn Idm sdng theo tidu chuln DSM-IV vd NINCDS-ADRDA phdn logi sa sut trf faJd theo thang Aim CDR.
Vietnam Joumal of Physiology 15(2), 8/2011 ISSN: 1859-2376
- Cdc bdnh nhdn duac chgp MRI sg ndo.
Nghidn cdu hinh dnh cgng hudng t u ' , tinh thi tich viing hai md vd khoang each lien mdc trdn phin mIm Dr.V^ew/Linux 5.0 (Asahi Kasei Joho System, Tokyo, Nhgt Ban), tai b^
mdn Sinh ly hgc-Hgc vign Qudn y.
- S6 lidu xd IJ theo phuang phdp thong kd y hgc blng phan mIm SPSS 16.
3. K ^ QUA NGHIEN Cl>U
3.1. Dae dilm lam sang cua nhdm bdnh nhan Alzheimer
Cdc ddc dilm Idm sdng chung ve tuoi khdi phdt, cdc tridu chdng khdi phdt vd ty Ig tridu Chung khdi phdt dug'c trinh bdy tren cdc bang 1 - 3 , diem trie nghidm than kinh tdm ly va phan logi theo diem CDR fa^dn cac bang 4, 5.
Bang 1. Tuli khdi phdt bdnh.
Tuoi M\d\ phdt b^nh
<60 60-69 70-79
>80 Ting si
Nhom Alzheimer (n = 38) S6 loong
7 31
0 0 38
Tyl?(%) 18,4 81,6 0 0 100 Kit qud trdn bdng 1 cho thiy tuli khdi
phdt bdnh trong nhdm bdnh nhdn Alzheimer hlu hit trong dd tuli 60 - 69 (81,6%), s i It han khdi phdt d dd tuli dudi 60 (18,4%), vd khdng cd trudng hg'p nao khdi phdt bdnh d dd tuli trdn 70 (p < 0,05).
Tuli khdi phdt bdnh trung binh Id 64,82 ±
4,99. Tuli khdi phdt cOa cdc bgnh nhdn Alzheimer trong nghidn cdu cOa chOng tdi chi3 y l u dt/a vdo cdc thdng tin khai thdc duac d ngudi nhd bdnh nhdn, ngudi chdm sdc cho bdnh nhdn, tridu chdng khdi phdt thudng Id cdc trigu chdng v l trl nhd vd ngdn ngd.
Bdng 2. Tri$u chOng khai phdt b$nh.
Tri^u ChOng khdi phdt Qudn
LSn lOn Khd tim to Qudn -1^ Ldn l$n Qudn + Khd tim tO Lin Idn + Khd tim to QuSn + Lln Idn + Khd tim tO
Nhom Alzheimer (n = 38) Sd locng
27 1 0 3 5 0 2
Tyia(%) 71,1
2,6 0 7,9 13,2
0 5,3 Kit qud trdn bdng 2 cho thdy triSu chOng
qudn Id phi biln nhdt (97,4%). Cdc tnrcrng hg'p cd phii hg'p giOa quin, iiin l$n vd khd tim
to chilm 21.1%. S i trudng hdp cd ca ba trilu ChOng ndy chilm 5.3% vd s i ngu^i cd t r i ^ chOng khdi phdt iSn Ipn Id it nhdt (2.6%).
^ -S- S- '3 5 S E
I I
siSSit
•i •'s -'s E =;« S •£
1 Nhdm Alzheimer (n
i^
'JE c
1
•TOo 12,63 10,06 6,84
Test Boston Kl tdn cdc con v|t 5,16 Nhd Iai 10 to ngay 0,97
1
E
•8 o i? b Z
1,91 1 NhdnbidtlOtOcdtrihoSn 1,44 Ke Iai cdu chuy§n ngay 0,5 Ke Iai cdu chuypn cd tri hodn 2,03 Nho Iai 10 hinh dnh ngay 1,16 Nhd l?110 hinh cd tri hodn 3,88 Nhdn bilt 10 hinh cd tri hodn 5,63
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•O :3 X CJ o-
o
2,16
t
> i KD T3 O b-
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2,19
o x:
c
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>
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8,84 10.81 2.88
Bdnh gid chOc ndnq thoc hi$n Tic dd vdn ddng thi gidc Thang trim cdm lao khoa 3.00
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Vietnam Joumal of Physiology 15(2), 8/2011 ISSN: 1859-2376
Trong nghidn cdu cOa chung tdi, dilm trie nghidm tdm thin til thieu (MMSE) trung binh cua cdc bgnh nhdn Alzheimer Id 12,63 ± 4.87, thIp han so vdi gid tri ndy d ngudi binh thudng (p < 0,05). Cac kit qua trie nghidm thin kinh tdm ly khdc d bdnh nhan Alzheimer cOng diu thIp han so vdi d ngudi binh
Bdng 5. MdcdgsasDt
thudng. Trong qua trinh nghidn cdu cua chung tdi cd 6 bdnh nhan sa siit tri tud (SSTT) nang. khdng thyc hidn duvc cdc trac nghi«n than kinh tdm ly, nhung chung tdi van dua vao nghien cdu vi nhdng bdnh nhdn ndy vdn phu hap vdi tidu chuln chin dodn bgnh Alzheimer theo tieu chuln DSM-IV (bang 5).
tri tug theo dilm CDR.
MOc dp Khdng SSTT (CDR = 0) MCI (CDR = 0,6) SSTT nhp (CDR =1) SSTTvOa(CDR = 2) SSTT nlng (CDR = 3)
Nhdm Alzheimer (n = 38) S i loong
0 0 4 20 14
TptCA) 0 0 10,5 52,6 36,8 Thang dilm CDR phdn dd SSTT, ngay nay
dd dug'c sd dgng nhu mdt tidu chuln cho vide ddnh gid SSTT trdn Idm sdng. Theo thang dilm phdn logi CDR, phin Idn cdc bdnh nhdn bj bdnh Alzheimer cd SSTT vda (52,6%) vd ndng (36,8%), cdn SSTT nhg chilm ty Id It nhit (10,5%).
3.2. Tirang quan gida biln d l l t h i tich hdi md vdi d$c dilm lam sdng cOa bdnh Alzheimer
D l CM thi cho vide ddnh gid tuang quan gida thi tfch hai ma vdi cdc tridu chdng lam
sdng d nhdm bdnh nhdn Alzheimer, chCing tdi tinh hg so tuang quan r theo mdc dd SSTT trdn Idm sdng cua thang dilm CDR. Do mdu nghidn cdu nhd ndn chQng tdi tinh hd so tuang quan r theo test Speamian (hd s6 tuang quan r.). Cdc kit qud nghidn edu v l tuang quan giua the tich hai md ehung vdi mdt s i tridu chdng Idm sdng d cdc nhdm t}dnh nhdn SSTT mdc dd nhg, vda vd ndng duac trinh bdy tren cdc bang 6 - 8, vd vdi diem trie nghigm than kinh tdm ly trdn bang 9.
Bdng 6. Tuang quan gida t h i tich hdi ma chung vdi cdc trigu chdng Idm sdng d nhdm bdnh nhdn SSTT mdc dd nhg (diem CDR = 1).
Cdc tridu chOng lam sdng R I I loan tri nhd ngdn hgn Rii loan trl nhd todn bd Rli loan ngdn ngO Mit dCing d$ng tdc Mit nhdn bilt
Gidm khd ndng xO ly khdng gian Gidm SI/ chd y thj gidc
r.
0,08 0,04 -0,33 0,08 -0,06 0,013 -0.17
P
>0,06
>0,05
>0.05
>0.05
>0.05
>0.05
>0.05
The tich hai ma giam khdng cd sy tuang Idm sang d nhdm bgnh nhdn Alzh^mer b\
quan vdi cdc rli loan tri nhd, chii y" v.v... trdn SSTT mdc do nhg (p > 0,05).
Bdng 7. Tuang quan gida thi tich hai md chung vdi cdc tridu chdng Idm sang d nhdm bdnh nhdn SSTT mdc do vda (dilm CDR = 2).
Cdc trieu ChOng lam sdng Rli loan tri nhd ngdn han
Rli loan tri nhd todn bp Roi loan ngdn ngO Mdt dung dpng tdc Mat nhdn bilt
Giam khd ndng xO ly khdng gian Giam so chu y thj gidc
rs 0.59 0.43 0.43 -0.59 -0.24 0.18 -0.05
P
<0.05
<0.05
>0.05
<0.05
>0,05
>0,05
>0,05 Vdi cdc bdnh nhdn Alzheimer SSTT hinh Id tuang quan thudn vdi rli logn tri mdc dd vda, t h i tich hai md cd si,p tuang nhd ngan vd ddi hgn (p < 0,05) vd tuang quan mdc d^ trung binh vdi mdt s i tridu quan nghjch vdi bilu hidn mit dung ddng chdng hay gdp trdn Idm sdng, diln tdc (p < 0,05).
Bdng B. Tuang quan gida thi tich hdi mS chung vdi cdc tridu ehdng 1dm sdng d nhdm bdnh nhdn SSTT mdc dd ndng (dilm CDR = 3).
Cdc tii$u chOng idm sdng Rli loan tri nhd ngln han
Rli loan tri nhd todn b | Rli loan ngln ngO Mit dfing ddng tdc Mat nhdn bilt
Giam khd nang xO ly khdng gian Gidm SV chO i thi gidc
r.
0.82 0.59 0.89 -0.89 0,78 -0.78 -0,45
P
<0.05
<0.05
>0,05
<0.05
>0,05
>0.05
>0.05 Kit qud trdn bang 8 cQng cho thiy cd sv
tuang quan gida t h i tich hdi md vdi mdt so trigu chdng hay gdp trdn Idm sdng, cu t h i Id vdi rli logn tri nhd vd vdi mit dung ddng tdc d cdc bdnh nhdn Alzheimer cd SSTT mdc dd n|ng. Cf nhdm bdnh nhdn ndy tridu chdng rli logn tri nhd ngln hgn tuang quan thudn mdc dg mgnh vdi t h i tich hdi md (ri=
0,82, p < 0,05), r l i logn tri nhd todn bd
tirang quan thudn mdc dd vda (rt= 0,59, p
< 0,05) vd trigu ehdng mit dung ddng tdc tuang quan nghjch mdc dd mgnh vdi t h i tich hai md (r, ~ -0,89, p < 0,05), trong khi cdc trigu ehdng cdn Igi ve rli logn ngdn ngd, mat nhgn bilt, giam khd ndng xd \') khdng gian, giam si/ chO y thj gidc diu khdng cd sv tuang quan vdi t h i tich vDng hai md (p > 0,05).
Vietnam Joumal of Physiology 15(2). 8/2011 ISSN: 1859-2376
Bdng 9. Toong quan gii>a thi tich hai ma vdi diem trie nghiem thin kinh tarn ly tren lam sdng.
Cdc chl tidu lam sang MMSE
Nhd to Tri nhd hinh So chu )f Ngdn ngO
Xdy dong hinh dnh qua thi gidc
Trdc nghidm v l ddnh gid chOc nang thoc hidn Tic d$ vdn ddng thi gidc
Thang trim cdm lao khoa Hoat ddng hdng ngdy
r 0.51 0.71 -0.02 0.22 0.15 0.11 0.33 0.26 0,17 0,24
P
<0,05
< 0,001
>0,05
>0.05
>0.05
>0.05
>0.05
>0.05
>0,05
>0.05 Kit qud trdn bang 9 cho thiy t h i tich
VLing hdi ma tuang quan thudn mdc dg vda vdi ting dilm cua trie nghidm MMSE (r = 0,51, p < 0,05) vd mdc dd mgnh vdi diim trie nghidm nhd td (r=: 0,71, p < 0,001) trdn cdc bdnh nhdn Alzheimer. ChOng tdi khdng thiy ed si/ tuang quan gida t h i tich vCing
hdi md vdi cdc trdc nghigm than kinh tdm ly khdc (p > 0,05).
3.3. Tuang quan gida biln d l i khodng cdch lidn mdc vdi d$c dilm lam sdng cOa bgnh Alzheimer
Cac kit qud nghidn cdu v l khla cgnh ndy duac trinh bdy trdn cdc bang 10 v d i 1.
Bdng 10. Tuang quan giua khoang cdch lidn mdc vdi cdc trigu chdng Idm sdng d nhdm t)dnh nhdn Alzheimer.
Cdc tri$u ChOng Idm sdng Rli loan tri nhd ngan han
Rii loan trf nhd todn b | Rli loan ngdn ngO Mit dOng d|ng tdc Mil nhdn bilt
Gidm khd ndng xO Ij khdng gian Gidm so chu y thj gidc
r -0.53
0.53 -0.26 0.32 -0.06 0.06 0.12
P
< 0,001
< 0,001
>0,05
<0,05
>0,05
>0,05
>0,05 Kit qud trdn bdng 10 cho ttily cd si/
tuang quan trung binh gida khoang cdch lidn mdc vdi mdt s i tridu chdng hay gdp trdn Idm sdng d nhdm bdnh nhdn Alzheimer, gim tuang quan nghjch mdc dd vi>a vdi ri^i logn tri nhd ngln hgn vd tuang quan thudn mdc dd
vda vdi rli logn tri nhd todn bd. Cdc roi logn cdn Igi (mit dDng dgng tdc, mat nhgn bilt, gidm khd ndng xu ly khdng gian vd giam su/
chii y thj gidc khdng thiy cd tuang quan vdi khoang cdch lidn mdc (p > 0,05).
Bdng 11. Tuang quan gida khodng each lien mdc vdi cdc chi so trie nghigm thin kinh tdm \^
tren lam sang.
Cac chi s i Idm sang MMSE
Nhd to Tri nhd hinh So chii f Ngdn ngO
Xdy dong hinh anh qua thj gidc
Trie nghidm v l ddnh gid choc ndng thoc hien Tic dp vdn dgng thj gidc
Thang trim cam lap khpa Hoat dpng hdng ngdy
r -0,49 -0.41 -0.31 -0.46 -0.45 -0.35 -0.04 -0.42 -0.1 -0.39
P
<0.01
<0.05
<0.05
<0.01
<0.01
<0.05
>0,05
<0,05
>0.05
<0.05 Dilm ciJa trie nghidm thin kinh tdm ly
MMSE, tri nhd, si/ ehd y, xdy d^ng htnh dnh qua thj gidc, toe dg vdn ddng thj gidc vd hogt ddng hdng ngdy cd sg> tuang quan mdc dg vda vdi khoang cdch lidn mdc (p < 0,05).
Thang dilm ddnh gid chde ndng thi/c hidn vd trim cdm ldo khoa khdng cd sy tuang quan vdi khoang cdch lien mdc (p > 0,05).
5. K£T LUAN
Nghidn cdu trdn 38 bdnh nhdn bj bdnh Alzheimer, kit qud cho thiy:
- D(^ tuli cua bgnh nhdn Alzheimer td 60 - 69 chilm 31,6%, td 70 - 80 chilm 47,4%.
- Tuli khdi phdt bdnh hay gdp td 60 - 69 (chilm 81,6%), tuoi khdi phdt trung binh Id 64,8214,99.
- Tridu chdng khdi phdt hay gdp Id qudn (71,1%), rli logn trl nhd ngln hgn (57,9%), rli logn tri nhd todn hg (42,1%), rli logn ngdn ngd (92,1%), mit diiing dgng tdc (57,9%), mit nhdn bilt (55,3%), giam khd nang xd ly khdng gian (73,7%), gidm chi3 #thj gidc (57,9%).
- Thi tich virng hdi ma d nhdm bdnh nhdn SSTT vda tuang quan thudn vdi tridu chdng
rli logn trl nhd ngan hgn, rli logn tri nhd todn bg (r. = 0,59 vd 0,43); tuang quan nghjch vdi tridu ehdng mit sd dung ddng tdc (rt= -0,59).
Cf nhdm bdnh nhdn SSTT ngng, thi tich viling hai md tuang quan thudn vdi tridu chdng rli logn trl nhd ngln hgn vd tri nhd todn bg (r, = 0,82 vd 0,59), tuang quan nghjch vdi tridu chdng mit su dyng dgng tdc (r, = -0,89). The tich VLing hai md ed si/ tuang quan thudn vdi dilm MMSE vd trie nghidm nhd td (r = 0,51 vd 0,71).
Khodng each lidn mdc tuang quan nghjch vdi roi logn tri nhd ngln hgn (r = - 0,53), tuang quan thugn vdi rli logn tri nhd todn bd vd mit sd dgng ddng tdc (r = 0,53 vd 0,32), tuang quan thudn vdi d i ^ MMSE (r = 0,49), tuang quan nghjch vdi trie nghidm nhd tu, nhd hinh, si/ chO y, ngdn ngd vd hogt ddng hdng ngdy (r = -0,41; -0,31; -0,46; -0,45 vd -0,39).
TAI L I $ U THAM KHAO
1. Nguydn Duy B I C , Hodng Vdn Luang, Ld Vdn Son, Trin Hdi Anh (2009) Nghidn cdu biln dli t h i tich hdi md d
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bdnh nhdn Alzheimer. Tgp chi Sinh ly hgc 13(3):tr.1-9.
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NXB Y hgc, Hd Ndi: tr.34-40.
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(2005) Memory encoding in Alzheimer, disease: An fMRI study of exiicit and implicit memory. Brain 128(Pt 4):773-787.
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SUMMARY Study correlation between clinical symptoms with the interuncal distance and
hippocampal volume using MRI of the brain of Alzheimer's disease patients Nguyen Giang H o a \ Nguyen Duy Bac^
Nguyen Minh Hai'-\ Tran Hai A n h ^ Nguyen Van Chuong^ Hisao Nishijo'
* r / i e fStfi Master Course, 'iVIilitary Medical University, Vietnam, 'University of
Toyama, Japan
A prospective study conducted on 38 patients diagnosed Alzheimer's disease according to DSM-IV and NINCDS-ADRDA from 2010 October to 2011 April at the Unit of Memory Research, Department of Neuropsychiatry, National Institute of Gerontology. The patients were examined clinically, performed psychological tests, and took MRI of the brain. The severity of their state was classified by CDR scale. The results showed that the number of patients having short-term memory disturbance was 59.7%, comprehensive memory disturbance: 42,1%, aphasia: 92.1%, and ataxia was 57.9%. The number of patients having a score by CDR = 1 was 10.5%. CDR = 2: 52.6%, and CDR = 3:
36.8%. Severe patients (CDR = 3) showed a po^tive correlation between hippocampal vcAume and the short-term and crmiprehenslve memory disturbance (rs 0.82 and 0.59, respectively). The interuncal distance in the Alzheimer's disease patients correlated with short-term and compmhensive memory disturbance (r = -0.53 and 0.32.
re^ectively).
Key words: Alzheimer's disease, interuncal distance, hippocampal volumes
