KADAR ASAM URAT SERUM RENDAH MENINGKATKAN RISIKO GANGGUAN FUNGSI KOGNITIF PADA USIA LANJUT.

TESIS

KADAR ASAM URAT SERUM RENDAH
MENINGKATKAN RISIKO GANGGUAN FUNGSI
KOGNITIF PADA USIA LANJUT

PUTU GDE ROTHAARNADA

PROGRAM PASCASARJANA
UNIVERSITAS UDAYANA
DENPASAR
2016

Lembar Pengesahan

TESIS INI TELAH DISETUJUI
PADA TANGGAL 11 OKTOBER 2016

PEMBIMBING I,

PEMBIMBING II,

Dr.dr. A.A.A. Putri Laksmidewi, Sp.S(K)
NIP 19630403 198803 2 003

dr. I Made Oka Adnyana, Sp.S(K)
NIP 19561010 198312 1 001

Mengetahui,

Ketua Program Studi Ilmu Biomedik
Program Pascasarjana
Universitas Udayana

Direktur
Program Pascasarjana
Universitas Udayana

Dr.dr. G.N. Indraguna Pinatih, M.Sc, Sp.GK
NIP 19580521 198503 1 002

Prof.Dr.dr. A.A. Raka Sudewi, Sp.S(K)
NIP 19590215 198510 2 001

i

Tesis Ini Telah Diuji Oleh Panitia Penguji
Pada Tanggal: 11 Oktober 2016

Berdasarkan SK Rektor Universitas Udayana
Nomor: 4951/UN14.4/HK/2016, Tanggal 7 Oktober 2016

Ketua

: Dr.dr. A.A.A. Putri Laksmidewi, Sp.S(K)

Sekretaris : dr. I Made Oka Adnyana, Sp.S(K)
Anggota :
1. dr. A.A.B.N. Nuartha, Sp.S(K)
2. Dr.dr. D.P.G. Purwa Samatra, Sp.S(K)
3. dr. I.G.N. Purna Putra, Sp.S(K)

ii

DAFTAR ISI
Halaman
SAMPUL DALAM ................................................................................................
i
PRASYARAT GELAR ......................................................................................... ii
LEMBAR PENGESAHAN ................................................................................... iii
KETETAPAN PANITIA PENGUJI ...................................................................... iv
SURAT PERNYATAAN BEBAS PLAGIAT........................................................ v
UCAPAN TERIMA KASIH .................................................................................. vi
ABSTRAK ............................................................................................................. xi
ABSTRACT ........................................................................................................... xii
DAFTAR ISI .......................................................................................................... xiii
DAFTAR TABEL .................................................................................................. xv
DAFTAR GAMBAR ............................................................................................. xvi
DAFTAR SINGKATAN ....................................................................................... xvii
DAFTAR LAMPIRAN ........................................................................................... xviii
BAB I

PENDAHULUAN .............................................................................
1.1 Latar Belakang ..............................................................................
1.2 Rumusan Masalah .........................................................................
1.3 Tujuan Penelitian .........................................................................
1.4 Manfaat Penelitian ......................................................................
1.4.1 Manfaat ilmiah ...................................................................
1.4.2 Manfaat praktis ....................................................................

1
1
6
6
6
6
6

BAB II

TINJAUAN PUSTAKA .....................................................................

2.1 Kognitif ........................................................................................
2.1.1 Gangguan fungsi kognitif pada proses penuaan ..................
2.1.2 Manifestai gangguan kognitif ..............................................
2.1.3 Tahapan penurunan fungsi kognitif .....................................
2.1.4 Pemeriksaan fungsi kognitif ................................................
2.2 Asam Urat ....................................................................................
2.2.1 Metabolisme asam urat .......................................................
2.2.2 Peranan asam urat ................................................................
2.3 Asam Urat dan Gangguan Fungsi Kognitif ..................................

7
7
7
11
14
17
19
19
22
25

BAB III

KERANGKA BERPIKIR, KONSEP DAN
HIPOTESIS PENELITIAN .................................................................
3.1 Kerangka Berpikir .........................................................................
3.2 Kerangka Konsep ..........................................................................
3.3 Hipotesis Penelitian ......................................................................

33
33
36
37

xiii

BAB IV

METODE PENELITIAN ..................................................................
4.1 Rancangan Penelitian ...................................................................

4.2 Tempat dan waktu penelitian .......................................................
4.3 Ruang Lingkup Penelitian ...........................................................
4.4 Populasi dan Sampel Penelitian ...................................................
4.4.1 Populasi target .....................................................................
4.4.2 Populasi terjangkau .............................................................
4.4.3 Kriteria sampel ....................................................................
4.4.3.1 Kriteria inklusi .........................................................
4.4.3.2 Kriteria eksklusi ......................................................
4.4.4 Besar sampel ........................................................................
4.4.5 Teknik pengambilan sampel ................................................
4.5 Variabel Penelitian .......................................................................
4.6 Definisi Operasional Variabel ......................................................
4.7 Alat Pengumpul Data ...................................................................
4.8 Prosedur Penelitian ......................................................................
4.9 Pengolahan dan Analisis Data .....................................................

38
38
39
39

39
39
39
39
40
40
41
42
42
42
48
49
51

BAB V

HASIL PENELITIAN ........................................................................
5.1 Analisis Deskriptif Subyek Penelitian .........................................
5.2 Hubungan Kadar Asam Urat Serum Rendah Dengan GFK
Pada Lansia ..................................................................................

5.3 Hubungan Faktor-Faktor Lain Yang Berpengaruh Terhadap
Terjadinya GFK Pada Lansia ........................................................
5.4 Faktor Risiko Independen Terhadap GFK ...................................

52
52

PEMBAHASAN ................................................................................
6.1 Karakteristik Dasar Subyek Penelitian .........................................
6.2 Hubungan Kadar Asam Urat Serum Rendah dengan GFK
Pada Lansia ..................................................................................
6.3 Hubungan Faktor-Faktor Lain Terhadap Kejadian GFK
Pada Lansia ..................................................................................
6.4 Faktor Risiko Independen Terhadap GFK ...................................

59
59

BAB VI

BAB VII

55
56
57

60
63
73

SIMPULAN DAN SARAN ............................................................... 75

DAFTAR PUSTAKA ............................................................................................ 76
LAMPIRAN-LAMPIRAN .................................................................................... 82

xiv

DAFTAR TABEL
Tabel 2.1
Tabel 2.2

Tabel 5.1
Tabel 5.2
Tabel 5.3
Tabel 5.4

Halaman
Golongan obat-obat yang mempengaruhi kadar asam urat
serum dan mekanisme kerjanya ........................................................ 22
Beberapa penelitian hubungan asam urat dan gangguan fungsi kognitif..............................
Karakteristik Dasar Subyek Penelitian
........................................ 53
Analisis Bivariat Kadar Asam Urat Serum Rendah dengan
GFK Pada Lansia ............................................................................. 55
Hubungan faktor-faktor lain yang berpengaruh
Terhadap terjadinya GFK pada lansia
.......................................... 56
Analisis multivariat regresi logistik
............................................. 58

DAFTAR GAMBAR
xv

Gambar 2.1
Gambar 2.2
Gambar 2.3
Gambar 2.4
Gambar 3.1
Gambar 3.2
Gambar 4.1
Gambar 4.2

Halaman
Hubungan faktor risiko dengan penyakit degeneratif pada lansia 10
Bagan metabolisme purin dalam tubuh manusia ........................... 20
Peran xanthine oxidoreductase (XOR) pada iskemia-reperfusi ..... 27
Mekanisme selular neuroprotektif oleh urat .................................. 30
Bagan Kerangka Berpikir ............................................................... 35
Bagan Kerangka Konsep ................................................................ 36
Bagan Rancangan Penelitan ........................................................... 38
Bagan Alur Penelitian .................................................................... 50

DAFTAR SINGKATAN

xvi

AUS
ADL
APOE
APP
CI
DM
DSM
GFK
ICD-10
IMT
JNC VIII
KTP
LDL
LFG
MCI
MMSE
MoCA
MS
NAD+
NO
OAT
OR
PA
Perdossi
Perkeni
PP
ROS
RNS
UOx
URAT1
WHO
XDH
XO
XOR

: Asam Urat Serum
: Activity of Daily Living
: Apolipoprotein E
: Amyloid PrecursorProtein
: Confidence Interval
: Diabetes Mellitus
: Diagnostic and Statistical Manual of Mental Disorder
: Gangguan Fungsi Kognitif
: International Classification of Disease 10th revision
: Index Massa Tubuh
: Eight Joint National Committee Classification
: Kartu Tanda Penduduk
: Low Density Lipoprotein
: Laju Filtrasi Glomerulus
: Mild Cognitive Impairment
: Mini Mental State Examination
: Montreal Cognitive Assessment
: Multipel Sklerosis
: Nicotinamide adenine dinucleotide
: Nitric Oxide
: Organic Ion Transporter
: Odds Ratio
: Penyakit Alzheimer
: Perkumpulan Dokter Spesialis Saraf Indonesia
: Perkumpulan Endokrinologi Indonesia
: Penyakit Parkinson
: Reactive Oxygen Species
: Reactive Nitrogen Species
: Urate Oxidase
: Urat Transporter 1
: World Health Organization
: Xanthine dehydrogenase
: Xanthine oxidase
: Xanthine oxidoreductase

DAFTAR LAMPIRAN

xvii

Lampiran 1
Lampiran 2
Lampiran 3
Lampiran 4
Lampiran 5
Lampiran 6
Lampiran 7
Lampiran 8
Lampiran 9
Lampiran 10

Halaman
Informasi Pasien ...................................................................... 82
Formulir Persetujuan tertulis .................................................... 84
Lembar Pengumpul Data .......................................................... 85
MoCA-Ina ................................................................................. 88
Skala Penilaian Depresi Hamilton ............................................ 89
(Tabel 2.1) Beberapa penelitian berhubungan dengan
asam urat dan gangguan fungsi kognitif ................................... 95
Keterangan Kelaikan Etik ......................................................... 96
Surat Ijin .................................................................................... 97
Data Subyek Penelitian ............................................................. 98
Hasil analisis SPSS 22 ............................................................. 104

xviii