Mild Cognitive Impairment:
Diagnosis and Treatment
Estimated Prevalence
• 10 ~ 20% over the age of 65
(Plassman et al, 2008)
Prevalence in Korea
• 65세 이상 노인 중 치매환자는 8.4%, 42만 명 추정
• 매년 20년마다 치매 환자 수 2배 증가
* 경도 인지장애: 동일 연령대에 비해 인지기능이 떨어져 있는 상태.
일상생활을 수행하는 능력은 보존되어 있어 아직 치매가 아니나 치매 전단계로 간주됨
보건 복지부 2008 치매 유병률 조사
Risk factors in patients with MCI
 Prevalence of MCI increases with age and men at higher risk
 Lower educational level
 Vascular risk factors (eg. DM, HT)
 Apolipoprotein E e4 genotype
 Vitamin D deficiency
 Sleep disordered breathing
 Prior critical illness (eg, Sepsis)
Plasman et al. 2008; Yaffe et al. JAMA 2011; Iwashyna et al. JAMA 2010
아밀로이드 양성 경도인지장애
5
Courses of Dementia
Onset of objective cognitive decline
Impairment on a cognitive test
Cognitive performance
BIOMARKERS
Age-, Sex-- & education adjusted normal performance range
Impairment on a ADL
Preclinical stage
SCD
MCI
Dementia
TIME
Biomarkers for Pre-dementia syndrome
Marker for Pathology
Marker for Neurodegeneration
Jack, Knopman et al.72013
Approach for diagnosis and managing
patient with MCI
Figure. Suggested Approach for Diagnosing and Managing Mild Cognitive Impairment
Concern regarding a decline in cognition obtained from patient, informant, or clinician, or as the result of worsening
performance on cognitive testing
Perform history focused on the following:
Changes in cognitive function (onset, trajectory, examples)
Changes in functional status (activities of daily living and instrumental activities of daily living, especially a change in ability to manage finances)
Current prescription and over-the-counter medications
Neurological symptoms (vision, hearing, speech, sleep-disordered breathing, gait, and numbness and tingling)
Psychiatric symptoms (depression, anxiety, and behavioral or personality changes)
Perform physical and neurological examination
Perform laboratory testing including the following:
Complete blood cell count, electrolytes, glucose, calcium, thyroid function, vitaminB 12, and folate
Perform cognitive testing including the Montreal Cognitive Assessment (MoCA) or the MiniCognitive Assessment Instrument (Mini-Cog)
No
Evidence of mild cognitive
impairment from evaluation?
Reassure patient and family Perform
follow-up for reevaluation in approximately
6 months or with significant change in
status






Langa et al. JAMA 2014
Yes
Optimize vascular risk factor control
Treat depression if present
Address polypharmacy; stop medications that negatively affect cognitive fx
Optimize vision, hearing, and sleep-disordered breathing
Counsel patient and family on beneficial behaviors, safety, finances, long-term
care, and prognosis
Perform follow-up for reevaluation in approximately 6 months or with
significant change in status
Cognitive impairment
Subjective
memory
impairment
Not normal for age
Not demented
Cognitive decline
Essentially normal functional activities
Dementia
MCI
Memory impaired?
Amnestic MCI
Memory impairment
only ?
Amnestic MCI
single domain
Amnestic MCI
multiple domain
Non amnestic MCI
Single non-memory cognitive
domain impaired?
Nonamnestic MCI
single domain
Nonamnestic MCI
multiple domain
From Petersen RC 2004
Currently used diagnostic criteria for MCI
Currently used diagnostic criteria for mild cognitive impairment(MCI)
Revised Mayo Clinic Criteria (2003) [2,3]
Clinical Criteria:
●
Further Characterization:
Subjective(self or informant)
cognitive complaint
●
Objective cognitive impairment
●
Preserved independence in functional abilities
●
No dementia
Yes
No
Memory Impairment
Amnestic MCI
Non-amnestic MCI
Single Domain
Amnestic MCI
Single Domain
Non-amnestic
MCI Single Domain
Multiple Domain
Amnestic MCI
Multiple Domain
Non-amnestic
MCI Multiple Domain
NIA-AA Criteria for MCI due to AD (2011)[8]
Clinical Criteria:
●
●
●
●
Concern regarding a change in cognition
self/informant/clinician report)
Further Characterization(or purposes of research and/or clinical trials):
Diagnostic category
Biomarkers of Aß deposition(PET
or CSF Aß)
Biomarkers of Neuronal injury (tau,
FDG PET, MRI)
MCI Core Clinical Criteria
Conflicting/Untested
Conflicting/Untested
Preservation of independence in
functional abilities
MCI due to AD:
Intermediate likelihood
Positive/Untested
Positive/Untested
Not demented
MCI due to ADS: High
likelihood
Positive
Positive
MCI: Unlikely due to AD
Negative
Negative
Objective evidence of impairment in one or more
cognitive domains, typically including memory
DSM-V Diagnostic Criteria for Mild NCD (2013) [9]
Clinical Criteria:
●
level of
Evidence of modest cognitive decline from a previous
performance in one or more cognitive domains
(self/informant/clinician report or on objective measures of
cognitive performance)
●
Preserved independence in functional abilities
●
The cognitive deficits do not occur exclusively in
the context of a delirium
●
The cognitive deficits are not better explained by another
mental disorder(e.g., major depressive disorder,
schizophrenia)
●
No dementia
Further Characterization:
Specify potential underlying etiology*:
●
●
●
●
●
●
●
●
●
Alzheimer’s disease
Frontotemporal dementia
Lewy body disease
Vascular disease
Traumatic brain injury
Substance/medication use
HIV infection
Prion disease
Parkinson’s disease
Vega et al. Curr Psychiatry 2014
Spectrum of Neuropathology in clinically
diagnosed AD







AD
Depression
Vascular abnormalities
TDP-43
Agyrophilic Grain Disease (AGD)
Hippocampal Sclerosis
Frontotemporal disease
Monsell SE, et al. JAMA Neurol 2015;72:1124-31
Spectrum of Neuropathology in
clinically diagnosed MCI ?








AD
Depression
Vascular abnormalities
TDP-43
Agyrophilic Grain Disease (AGD)
Hippocampal Sclerosis
Frontotemporal disease
Other neurodegenerative disease: DLB, PSP, PD….
→ 증상이 아직 현저하지 않아 자세한 인터뷰와
진찰이 필요하고 분명히 알기 어려운 경우들이 많음.
추적관찰이 중요!!!!
Clinical characteristics of patients with amyloid
negative MCI from ADNI
Landau SM, et al. Neurol 2016;86:1377-85
Landau SM, et al. Neurol 2016;86:1377-85
MCI to AD progression in general practice – data from
the German AgeCoDe study
outcome after ~ 3 years (N=357)
Subtype at
study start
remittent
instabil
stabil nonprogressive
Progressive
single nonmemory
MCI
53%
24%
14%
10%
100%
multidomain nonamnestic MCI
29%
18%
18%
34%
100%
amnestic MCI
35%
13%
11%
41%
100%
multidomain
amnestic MCI
11%
21%
20%
48%
100%
total
42%
21%
15%
22%
100%
Lutz Frölich, 2013,
Treating and counseling patients with MCI
Box. Treating and Counseling Patients With Mild Cognitive Impairment
Control of Vascular Risk Factors and Prevention of Stroke
Social Needs
and Subclinical Brain Injury
• Encourage and facilitate social interactions
• Hypertension present
• Discuss living will, durable power of attorney, financial and
 Control blood pressure and avoid hypotension
• Diabetes present
 Control severe hyperglycemia and avoid severe
hypoglycemia
• Primary or secondary stroke prevention
long-term care plans
• Provide community resources for patient and caregivers
• Discuss driving safety
• Discuss home safety, including kitchen safety, firearms, poisons,
and potential fall risks
 Statin if indicated
• Atrial fibrillation present
 Initiate anticoagulant or antithrombotic therapy
if no contraindications
Prognosis and Follow-up
• Discuss current evidence and uncertainty regarding MCI
prognosis with patient and family
• Arrange follow-up approximately every 6 months to assess
Beneficial Behaviors
changes in cognitive function and potential evolving needs for
• Abstain from heavy alcohol or illicit drug use
social support
• Engage in mental activity
• Engage in physical activity
• Stop smoking
Langa et al. JAMA 2014
Pharmacological treatment trials in
patients with MCI
 Beneficial effects were not demonstrated in drug trials of
donepezil, galantamine and rivastigmine
Vega et al. Curr Psychiatry 2014
Pharmacological treatment trials in patients with MCI
Vega et al. Curr Psychiatry 2014
Efficacy of Ginkgo biloba
on MCI
Ginkgo biloba
•
•
•
•
•
•
•
•
Ginkgoaceae family
Also known as maidenhair tree
World’s oldest tree species
Thought to improve cerebral circulation,
anti-inflammatory, anti-oxidant
properties
Extract from the ginkgo tree (EGb761)
taken in doses of 120mg to 240 mg
daily
Trials show modest improvements in
some measures of function and
memory
Cognitive enhancer : may be beneficial
in reducing AD, but controversial
Reasonably safe and well tolerated, but
some side effects (GI, headache,
bleeding)
Chemical Composition
1. 은행엽건조엑스, 대한민국약전외한약(생약)규격집, 식품의약품안전처고시 제2019-9호
2. Ahlemeyer B et al., Cell Mol Life Sci. 2003 Sep;60(9):1779-92. (* 은행엽엑스의 유효성분 관련 검토사항 첨부(.msg))
Ginkgo biloba extract on Dementia
Ginkgo biloba extract on Dementia : Animal
Study
: Animal Study
Ginkgo biloba extract on Dementia : Clinical Trial
LaBars et al., JAMA 278:1327-1332, 1997
– USA study 6 research centers
– N=309, EGb (120 mg/d) or placebo
– 202 evaluable at 52 weeks ( evaluation at 12,
26, and 52 weeks)
• In ginkgo group had 1.4 point better than
placebo group on ADAS-Cog (p=0.04)
• GERRI score by caregivers : 0.14 points better
than placebo (p = 0.004)
• No difference was seen in CGIC
• adverse effects: same as placebo
– conclusions: modest improvement of cognition
of patients, but sufficient improvement
recognized by caregivers
■ Summary of expert consensus statements from the Asian Clinical Expert Group on
Neurocognitive Disorders (CNS Neurosci Ther. 2019;25:288–298.)
Ginkgo biloba extract has a role in the management of AD, VaD, BPSD, and MCI
Consensus statement 1a: Efficacy of Ginkgo biloba extract in
AD, VaD, and BPSD
Expert recommendation
For Ginkgo biloba extract
specifically:
Based on the available evidence, the Expert Group consider current best
practice for the pharmacological treatment of AD (±CVD), VaD, and BPSD to
be as follows (best practice may vary between countries):
AD: AChEI, memantine, Ginkgo biloba extract
VaD: AChEI, memantine, Ginkgo biloba extract, antiplatelet therapy
BPSD: ChEI, nonpharmacological treatment, antipsychotics (off‐label),
memantine, SSRIs, sedatives, and Ginkgo biloba extract
Class of recommendation
I; level of evidence A
Consensus statement 1b: Management of MCI
Ginkgo biloba extract may be considered for use in patients with MCI
Class of recommendation
IIB; level of evidence A
2010년 이후 publish 된 관련 문헌리스트(1)
Reference
연구설계
내용
Beck SM et al. Hum
Psychopharmacol. 2016
May;31(3):227-42
RCT
EGb 761®의 cognitive control functions, mental activity of
the prefrontal cortex and stress reactivity에 대한 효과 연구:
cognitive flexibility개선
Demarin V et al.
Neuropsychiatr Dis Treat. 2017
Feb 16;13:483-490
RCT
혈관성 인지 장애(VCI, vascular cognitive impairment)에 대
한 GBE 효과
: 90명 VCI 환자. GBE 120mg, 60mg, 위약군으로 무작위 배
정하여 6달간 복용. neuropsychological tests scores 측정
(Sandoz Clinical Assessment Geriatric Scale, Folstein MiniMental State Examination, Mattis Dementia Rating Scale,
and Clinical Global Impression)
: GBE는 Clinical Global Impression에서만 위약대비 유의한
효과를 나타냄.
: 이상반응은 위약군에서 오히려 유의하게 높게 나타남.
Evid Based Complement
Alternat Med.
2011;2011:164139
RCT
50-61세 노인 19명.
WM(working memory)를 요하는 작업을 하는 동안 더 효율
적인 processing과 관계가 있음.
2010년 이후 publish 된 관련 문헌리스트(2)
Reference
연구설계
내용
European Medicines Agency,
2015
EMA보고서
GBE can be used to improve the age-related cognitive
impairment (worsening of mental abilities) and quality of
life of adults with mild dementia.
(there are bibliographic data providing scientific evidence
of their effectiveness and safety)
Yuan Q et al. J Ethnopharmacol.
2017 Jan 4;195:1-9
Overview of
Systematic Reviews
GBE는 하루 200mg 이상(보통 240mg), 22주 이상 복용 시
위약과 대비하여 인지 기능, 일상 활동, clinical global
impression(치매치료)에 유익함
Zhang HF et al. Front Aging
Neurosci. 2016 Dec 6;8:276
Overview of
Systematic Reviews
GBE 치료는 인지 기능과 신경정신학적(neuropsychiatric) 증
상, daily activities 개선을 나타냈으며, 용량의존적이었음.
: 효과는 고용량(1일 240mg)에서 확실하게 나타남.
: 위약군과 이상사례 발현율은 유사하며 알츠하이머 그룹에
서는 어지럼증, 이명, 협심증, 두통에 대한 부작용이 오히려
더 적게 나타남(GBEs seem to be generally safe)
: (결론) GBE는 MCI와 치매에 효과가 있음
BMC Geriatr. 2010 Mar 17;10:14
Systematic Review
알츠하이머, 혈관성, 혼합성 치매 환자에서 GBE에 의한 인지
능에 개선이 있었음.
Gschwind YJ et al. Aging Clin
Exp Res. 2017 Feb 8. doi:
10.1007/s40520-016-0699-y
RCT
MCI 환자에서 dual tasking walking에 대한 GBE의 효과 : 50
명 GBE 120mg b.i.d. vs. 위약(6개월). 이후 6개월 open label
F/U
: GBE 투여군에서 dual-task-related cadence(걸음수)가 유의
하게 증가함
경청해 주셔서 감사합니다.