KONSENSUS NASIONAL

Peran Dokter Spesialis Penyakit Dalam

untuk Deteksi Dini, Diagnosis, dan
Penatalaksanaan Gangguan Kognitif Ringan
pada Usia Lanjut

PERGEMI
 Latar Belakang
Jumlah usia lanjut semakin meningkat
peningkatan masalah kesehatan terkait
meningkatnya usia
Salah satu masalah utama: penurunan fungsi
kognitif (ringan s.d. berat/demensia)
Selain faktor usia, beberapa faktor risiko vaskular
(DM, HT, dislipidemia, obesitas, dll) memudahkan
usila mengalami gangguan kognitif peran
SpPD penting
Perlu kesepahaman untuk menatalaksana usila
yang berisiko atau telah mengalami gangguan
kognitif ringan, agar tdk berlanjut menjadi
demensia yang berat
 Gangguan Kognitif Ringan
Mild Cognitive Impairment (MCI)
Sindrom pre-demensia
Sebagian berlanjut menjadi demensia (terutama AD)
dengan laju progresi cukup tinggi
Stadium yang sesuai untuk intervensi terapi
Vascular Cognitive Impairment (VCI)
Penurunan fungsi kognitif ringan
Dihubungkan dengan iskemia/infark jaringan otak
akibat penyakit vaskular atau aterosklerosis
Keadaan prodromal timbulnya demensia vaskular
(VaD)
 Progresi MCI Menjadi AD

Mild cognitive impairment

Probable penyakit Alzheimer

Fungsi
kognitif
Penyakit Alzheimer

Umur

Petersen dkk. Arch Neurol. 2001;58:1985-92

 Epidemiologi
Prevalensi
MCI: 3-15%*
VCI: 1,45%**
Insidens
MCI: 8,5-25,94/1000 person-year*
Laju progresi
MCI menjadi AD: 10-15% pertahun*
VCI menjadi demensia 44% dalam 5 tahun**
Di Poliklinik Geriatri RSCM: prevalensi MCI 20%***
*Panza dkk. Am J Psychiatry. 2005;13:633-44
**Wentzel dkk. Neurology. 2001;57:714-6
***Wardhani I. Tesis, FKUI. 2005
 Faktor Risiko
Tidak Dapat Dimodifikasi Dapat Dimodifikasi

Usia yang lanjut Tekanan darah tinggi

Jenis kelamin Diabetes melitus dan
Kondisi genetik: resistensi insulin
Mutasi pada APP Dislipidemia
Munculnya ApoE 4 Merokok
Trisomi-21
Obesitas
CADASIL
Gagal jantung
Fibrilasi atrium
Hiperkoagulasi dan
APP=amyloid precursor protein, ApoE=apolipoprotein E,
CADASIL=cerebral autosomal dominant arteriopathy hiperagregasi trombosit
with subcortical infarcts and leukoencephalopathy
 Faktor Risiko

Variabel Odds Ratio (OR)

Penyakit jantung koroner 2,55
Dislipidemia 2,35
Hiperagregasi trombosit 2,33
Diabetes melitus 2,15
Hipertensi 2,05

Hebert R, Canadian Risk Factor Study. Stroke 2000;(31)

 Effects of Hypertension
on Attentional Function
Low SBP Normal SBP High SBP
N=95 N=170 N=59
0

-1
Digit Symbol test score
10-year change on

-2

-3

-4

-5
Deterioration
-6
Swan.Swan. Neurology
Neurology. 1998;51:98693
1998;51:98693
 DM and Risk of Dementia
(The Rotterdam Study)
30 - 27.0

Adjusted
difference 7.7%
20 - (95% CI 1.9% to
% Diabetes 15.0%); p 0.005

10.5
10 -

No dementia Dementia at
at follow up*, follow up*,
N=6244 N=126
*2.1 years of follow-up

Ott et al. The Rotterdam Study. Neurology.1999;53:1937-42

 High Cholesterol and Risk of Dementia

40 -

36.9 Adjusted HR 1.42

(95% CI 1.22 to
35 - 1.66); p 0.0107
% High
Cholesterol**
31.7
30 -

No dementia Dementia at
at follow up*, follow up*,
N=8124 N=721
*30 years of follow-up
**Total serum cholesterol >240 mg/dL Whitmer et al. Neurology.2005;64:277-81
Direct effect of cardiovascular risk factors on the formation of
plaques and tangles and increased risk of dementia
Physical High High fat
inactivity BMI intake

Diabetes High BP High

cholesterol

Vascular
Smoking changes

ApoE4: poor
Neuronal Damage and repair
Degeneration

MCI VCI

AD VaD
 Early detection
Advanced age
Risk factors (high BP, DM, high cholesterol,
obesity, history of stroke, family history, etc)
Memory complaint (usually short-term memory)
with intact activities of daily living, other cognitive
disfunction (execution, problem-solving, working
memory)

Patient and family denial or doctors unawareness

make mild cognitive impairment usually undiagnosed
 Diagnosis
Neuropsychiatric examination for MCI/VCI
screening:
MMSE (score >24)
GDS (score 2 or 3)
CDR (score <0,5)
Diagnosis of MCI based on diagnostic criteria
proposed by Petersen et al. (2001)
Recently, no acceptable criteria for diagnosis of
VCI
Criteria for Amnestic Mild Cognitive Impairment

Memory complaint, preferably corroborated by informant

Impaired memory function for age and education
Preserved general cognitive function
Intact activities of daily living
Not demented

Petersen et al. Arch Neurol. 2001;58:1985-92

 Antihypertensive medications and
dementia RCTs (I)
SHEP 1991, 5 y follow-up
No difference in dementia incidence between the thiazide group and
placebo
(different drop-out rates may have influence the result)

Syst-Eur Forette et al. 1998, 2002

Isolated systolic hypertension antihypertensive treatment with a
calcium channel-blocker AD incidence by 50%

PROGRESS Tzourio et al. 2003

Treatment with an ACE-inhibitor and diuretics the risks of dementia
and cognitive decline associated with recurrent stroke by 34% and 45%
 Antihypertensive medications and
dementia RCTs (II)
SCOPE candesartan & cognition

Baseline MMSE score >24:

- 24-28low cognitive function (LCF)
- 29-30high cognitive function (HCF)
Follow-up 3.7y
Cognitive function well maintained in both treatment groups
In LCF patients, MMSE score decline less in the candesartan
than in control group

Lowering of blood pressure in elderly (70-89y) Lithell et al. 2003

with mild hypertension is beneficial and safe Skoog et al. 2005
 Statin treatment and dementia occurence

Wolozin et al., 2000

Jick et al., 2000
rates (up to 70%) of dementia and AD Rockwood et al., 2002
(observational)

Reitz et al., 2004

No association between statin Li et al., 2004
use and incidence of dementia Zandi et al., 2005
(prospective, short-term)

HPS Collaborative Group, 2002

No significant effect of statin PROSPER Shepherd et al., 2002
treatment on cognitive function
(randomized)
 Relation of diabetes treatment on
cognitive decline (after 2y of follow-up)

Type of OR for poor cognitive Mean difference in

treatment performance cognitive performance
(95% CI) (95% CI)

Insulin 1.38 -0.11

(0.97 to 1.95)a,b (-0.18 to -0.03)b
Oral medication 0.99 -0.06
(0.74 to 1.33)a (-0.11 to 0.01)
No reported 1.45 -0.08
treatment (1.04 to 2.02) (-0.15 to -0.01)

Not significant compared to subjects without diabetes

a

b
Subjects treated using insulin all have longer duration of
diabetes, worse control, and prevalence of hypoglycaemic attacks

Logroscino et al. BMJ. 2004;328:548-53.

Drugs for treating cognitive function
Anticholinesterase inhibitors: tacrin, donepezil,
rivastigmine, galantamine
N-methyl-D-aspartate receptor antagonist:
memantine
Antioksidan and other adjunctive treatments: -
tokoferol (vitamin E), ginkgo biloba, selegiline
Others (still controversies): estrogen replacement
therapy, antiinflammatory drugs, SERM
(raloxifene)
Non-pharmacological approaches: intensify
involvement in social life, cognitive stimulation
activity, mental and emotional stimulation
Vitamin E and Donepezil for the Treatment
of Mild Cognitive Impairment
Petersen et al. N Engl J Med. 2005;352:2379-88

Study Methods: Double-blind, subjects with the amnestic

subtype of mild cognitive impairment (769 subjects enrolled),
randomly assigned to receive 2000 IU of vitamin E daily, 10
mg of donepezil daily, or placebo for three years. The
primary outcome was clinically possible or probable
Alzheimers disease; secondary outcomes were cognition
and function.
 Vitamin E and Donepezil for the Treatment
of Mild Cognitive Impairment
Petersen et al. N Engl J Med. 2005;352:2379-88

All Subjects

Donepezil vs. placebo (HR, 95%CI): Vitamin E vs. placebo (HR, 95%CI):
First 12 mo 0.42 (0.24-0.76) First 12 mo 0.83 (0.52-1.32)
First 24 mo 0.64 (0.44-0.95) First 24 mo 0.95 (0.67-1.36)
All 36 mo 0.80 (0.57-1.13) All 36 mo 1.02 (0.74-1.41)
 Vitamin E and Donepezil for the Treatment
of Mild Cognitive Impairment
Petersen et al. N Engl J Med. 2005;352:2379-88

APOE 4 Carriers

Donepezil vs. placebo (HR, 95%CI): Vitamin E vs. placebo (HR, 95%CI):
First 12 mo 0.34 (0.16-0.69) First 12 mo 0.78 (0.46-1.34)
First 24 mo 0.54 (0.35-0.86) First 24 mo 0.95 (0.64-1.41)
All 36 mo 0.66 (0.44-0.98) All 36 mo 0.95 (0.66-1.36)
Evidence of efficacy of donepezil for people with
mild or moderate vascular cognitive impairment
Malouf and Birks. The Cochrane Database of Systematic Reviews, 2005.

Two large-scale, randomized, double-blind, parallel-group controlled trials,

enrolled of 1219 people with mild to moderate cognitive decline due to
probable or possible vascular dementia

Authors conclusions:
Evidence from the available studies support the benefit of donepezil in
improving cognition function, clinical global impression and activities of daily
living in patients with probable or possible mild to moderate vascular cognitive
impairment after 6 months treatment.
Extending studies for longer periods would be desirable to establish the efficacy
of donepezil in patients with advanced stages of cognitive impairment.
Moreover, there is an urgent need for establishing specific clinical diagnostic
criteria and rating scales for vascular cognitive impairment.
Peran Dokter Spesialis Penyakit Dalam

Deteksi dini dan diagnosis gangguan kognitif

ringan
Identifikasi faktor risiko dan optimalisasi
pengendalian/pengobatan faktor risiko (yg dpt
dimodifikasi)
Melakukan penatalaksanaan awal terhadap
gangguan kognitif ringan (farmakologis dan non-
farmakologis)
Melakukan upaya rujukan dini dan konsultasi
kepada spesialis terkait (psikiater, neurolog,
konsultan geriatri)
 KONSENSUS NASIONAL
Peran Dokter Spesialis Penyakit Dalam untuk
Deteksi Dini, Diagnosis, dan Penatalaksanaan
Gangguan Kognitif Ringan pada Usia Lanjut

ALGORITME Pasien usia lanjut dengan

keluhan memori
subyektif / dilaporkan
keluarga

Anamnesis: Faktor risiko: Laboratorium:

Lama keluhan Hipertensi Fungsi tiroid Kelola semua
Awitan Diabetes melitus Fungsi hati faktor risiko
Progresivitas Dislipidemia Fungsi ginjal sesegera &
Aktivitas hidup sehari-hari Merokok Kadar vitamin B12 seoptimal
Riwayat keluarga Obesitas Kadar obat dalam mungkin
Penggunaan obat-obatan dll darah

Modifikasi/terapi Terapi sesuai penyebab

bila ada bila abnormal

Optimalisasi
pengelolaan
Evaluasi fungsi kognitif dengan MMSE FOLSTEIN faktor risiko
 KONSENSUS NASIONAL
Peran Dokter Spesialis Penyakit Dalam untuk
Deteksi Dini, Diagnosis, dan Penatalaksanaan
Gangguan Kognitif Ringan pada Usia Lanjut

ALGORITME (LANJUTAN)

Lanjutkan pengelolaan faktor risiko:

Evaluasi fungsi kognitif dengan MMSE FOLSTEIN Terapi antihipertensi
Injeksi / obat hipoglikemik
MMSE <24 MMSE 24-28 MMSE >28 Obat penurun kadar lemak
Antikoagulan
Demensia MCI / VCI Normal(?) Olahraga yang teratur
Suplementasi asam folat & Vit. B12
Konsumsi serat larut air
Asupan kalori yang baik (proper
Edukasi Edukasi Evaluasi fungsi caloric intake)
Rujuk SpKJ / SpS / Inhibitor kolinesterase* atau kognitif tiap 6 Berhenti merokok
Konsultan Geriatri memantin*, ditambah bulan
antioksidan (vitamin E) atau ginko
biloba atau terapi tambahan lain
Kerjasama dgn spesialis terkait

Skor MMSE Skor MMSE

tetap / turun Evaluasi 6 bulan
meningkat