Mild cognitive impairmentMild cognitive impairment

[MCI][MCI]

Prof Ashraf AbdouNeuropsychiatry dept

Alexandria univ

Objectives•The concept of MCI•Criteria for diagnosis•Controversies about MCI•Prevalence of MCI•Outcome of MCI•Trials for treatment of

MCI

Cogntive abilities and age

Cognition: means of acquiring and processing information about our selves and our worldIncludes memory and other functions

Cognitive abilities peak in 30s

Plateau through 50s, 60s

Slow decline late 70s

Dementia

Memory deficit+

At least 1 other cognitive area affected

+Interfere with daily

activity

Mrs Um Alsaad a 60-yrs old lady, housewife describing her cognitive health as good till 2 yrs ago she and her children noticed her difficulty recalling where she place objects, her forgetfulness about recent conversations and difficult in remembering names.

She can do all her duties outside and inside the home.

Her MMSE 27

• Kral 1962; Benign senescent forgetfulness.

• NIMH 1986; Age-associated memory impairment (AAMI)

• Int Psychogeriatric association 1994; Age-associated cognitive decline (AACD)

• CSHA 1997; Cognitive impairment no-dementia (CIND)

• AAN 2001; Mild cognitive impairment (MCI)

Development of the concept of MCI

13000 publications till now in pubmed

NormalCognition

Prodromal Dementia

Dementia

Brain Aging

Mild CognitiveImpairment

Stable OrReversibleImpairment

OtherDementias

Alzheimer’sDisease

VascularDementia

Reversible

Mixed Mixed

MCI is Prodromal Dementia

MCI criteria1. Memory complaint,

preferably corroborated by an informant

2. Objective memory impairment for age

3. Normal general cognitive function

4. Intact activity of daily living

5. Not demented

Application of MCI criteria

First criteria refers to the subjective memory complaint.

What if the patient didn’t complaint?

Application of MCI criteriaSecond criteria refers to an

objective memory impairment for age.

–score 1-2 SD below their age-mates

MMSE low sensitivity for MCI

Montreal cognitive assessment [MoCA]

http://www.Mocatest.org

• Third criteria regarding general intellectual function. - General intellectual function ( other nonmemory cognitive domains, e.g. language, executive function, visuospatial skills ) - n o specific instruments or cutoff scores - Neuropsychological testing can be very useful

Application of MCI criteria

• Fourth: A ctivities of daily living The criterion requires that the

No f unctional impairment can be difficult to determine in older s

ubjects who may have several me dical comorbidities and physical li

mitations. • L ast criteria , 'not demented', is

also made on the basis of the clini cian's best judgement.

Application of MCI criteria

Prevalence

P revalence of mild cognitive impairment

vary from1 34% to %•Increase with age•Different assessment tools

Prevalence of MCIPrevalence of MCIAuthor (year)Author (year) N N Age Study Age Study Prevalence Prevalence

(%)(%)

Graham (1997) 1800 >65 CSHAGraham (1997) 1800 >65 CSHA 5.3 5.3

Larrieu (2002)Larrieu (2002) 1265 70-90 PAQUID 1265 70-90 PAQUID 2.8 2.8

Hanninen (2002) 806 60-76 KUPIOHanninen (2002) 806 60-76 KUPIO 5.3 5.3

Lopez (2003) 2470 >75 CHSLopez (2003) 2470 >75 CHS 6.06.0

Fisk (2003) 1790 >65 CSHAFisk (2003) 1790 >65 CSHA 1-31-3

Ganguli (2004) 1248 >65 MoVIESGanguli (2004) 1248 >65 MoVIES 3-4 3-4

• Typical MCI patient is one who has a memory impairment beyond what is felt to be normal for age but is relatively intact in other cognitive domains.

• The concept of MCI has been expanded to include other types of cognitive impairment beyond memory

Clinical Spectrum

Classification of MCI

MCI

Amnestic Non-amnestic

Single domain Multiple domainSingle domain

Multiple domain

Clinical subtypes of mild cognitive impairment

 Flow chart of decision process for makingdiagnosis of subtypes of MCI

Journal of Internal MedicineVol 256 Issue 3 Page 183, Sep2004

Exclusion of systemic or brain diseases that can cause cognitive decline

Depression - Memory function may improve with

treatment of depressionMetabolic disturbance

- Memory function may improve if correctedTraumatic injury

- Memory function often stabilizes after a period of recovery

Vascular disease - Memory function may stabilize or progress

Outcome of MCIOutcome of MCI

MCI

AD

Age

Cog

nitiv

e D

eclin

e

The annual rate of conversion to AD

10 – 15% per year

Outcome

FunctionFunction

AgeAge

Probable ADProbable AD

MCI Amnestic TypeMCI Amnestic Type

NormalNormal

Conversion to AD

Definite ADDefinite AD

Point of conversion

Outcome

Mayo Alzheimer's Disease Research Center

- 220, mean age 79 yrs, F/U 3-6 yrs

- Progressed from normal to

dementia at a rate of 12% per year

• Followed for up to 6 years approximately 80% of them will have converted to dementia

Mild Cognitive Impairment Mild Cognitive Impairment (MCI)(MCI)

MCI →AD 12%/yr Control→AD 1-2%/yr

Petersen RC et al: Arch Neurol 56:303-308, 1999

50

60

70

80

90

100

50

60

70

80

90

100

Initial 12 24 36 48exam Months

Initial 12 24 36 48exam Months

Clinical severity

Type; multiple domain vs single domain

Genetics: Apolipoprtein E-4 carrier

Biomarkers

Radiological

CSF

Outcome

Neuroimaging

Essential part of general evaluation in MCI subject

- Identifying specific and treatable cause of cognitive impairment (DDx)

- Markers for prediction of conversion to AD

Predict future development of AD

- Atrophy Hippocampus & entorhinal cortex ( MRI ) - Evidence deficits in - regional cerebral blood flow as measured by SPECT - regional cerebral glucose as measured by FDG-PET

Neuroimaging

  Arrow highlights the body of the hippocampus. Image on right is from a patient w

ith atrophy.

Arrows mark the entorhinal cortex on MRIArrows mark the entorhinal cortex on MRI.

(CSF) biomarkers

• Invasive procedure•Lack of normative data

no change of these CSF markers with age

•Effect of drugs on change in CSF markers

(CSF) biomarkers

3 cerebrospinal fluid (CSF) biomarkers

- - -total tau (T )

- - -phospho tau (P )

- 42 amino acid form of β- amyloid

(Aβ42)

TREATMENT

•Dopenzil-Vit E-Placebo study 2005

•Galantamine trial; 2004•Rivastigmine trial; 2004•Rofecoxib trial; 2005•Ginko biloba; 2008• 12Folic acid vitamin B trial;

2004• Lithium; some benefit 2011

Fail to show any benefit

Treatment

What to do?

• Exercise

• Healthy food

• Cognitive stimulating activities

• Stop smoking

• Control; DM, HTN, Dyslipedemia

• Treat depression

Tying it all together!Tying it all together!

MCI is a widely MCI is a widely accepted term for accepted term for diagnosis of diagnosis of memory memory impairment not impairment not fulfilling the fulfilling the criteria of dementiacriteria of dementia

Diagnostic criteria Diagnostic criteria need to be need to be standardized, to standardized, to include it in the include it in the current current classifications.classifications.

Tying it all together!Tying it all together!

Biomarkers are Biomarkers are the main focus of the main focus of research nowresearch now

Current treatment Current treatment options are options are control of risk control of risk factors and factors and healthy lifestylehealthy lifestyle