MILD COGNITIVE IMPAIRMENT

1. Mild cognitive impairment
[MCI]
Prof Ashr af A bdou
Neuropsychiatry dept
Alexandria univ

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

3. Cogntive abilities and age
Cognition: means of acquiring and
processing information about our selves
and our world
Includes memory and other functions
Cognitive abilities peak in 30s
Plateau through 50s, 60s
Slow decline late 70s

4. Dementia
Memory deficit
+
At least 1 other cognitive
area affected
+
Interfere with daily activity

5. 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

6. Development of the concept of
MCI
• 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 nodementia (CIND)
• AAN 2001; Mild cognitive
impairment (MCI)

7. 13000 publications till
now in pubmed

8. MCI is Prodromal Dementia
Normal
Cognition
Dementia
Reversible
Prodromal
Dementia
Brain Aging
Mild Cognitive
Impairment
Stable Or
Reversible
Impairment
Alzheimer’s
Disease
Other
Dementias
Mixed
Vascular
Dementia
Mixed

9. MCI criteria
1. 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

10. Application of MCI criteria
First criteria refers to the
subjective memory
complaint.
What if the patient didn’t
complaint?

11. Application of MCI criteria
Second criteria
refers to an
objective memory
impairment for
age.
–score 1-2 SD
below their agemates
MMSE
low
sensitivity for MCI
Montreal
cognitive
assessment
[MoCA]
http://www.Mocates
t.org

12. Application of MCI criteria
general
intellectual function.
• Third criteria regarding
- General intellectual function (other
nonmemory cognitive domains, e.g.
language, executive function,
visuospatial skills )
- no specific instruments or cutoff
scores
- Neuropsychological testing can be
very useful

13. Application of MCI criteria
• Fourth: Activities of daily living
The criterion requires that the
No
functional impairment can be
difficult to determine in older sub
jects who may have several medi
cal comorbidities and physical li
mitations.
• Last criteria, 'not demented', is
also made on the basis of the clin
ician's best judgement.

14. Prevalence
Prevalence of mild cognitive
impairment
vary from 1% to 34%
•Increase with age
•Different assessment tools

15. Prevalence of MCI
Author (year)
Graham (1997)
N
1800
Age
Study
Prevalence (%)
>65
CSHA
5.3
Larrieu (2002)
1265
70-90
PAQUID
2.8
Hanninen (2002)
806
60-76
KUPIO
5.3
Lopez (2003)
2470
>75
CHS
6.0
Fisk (2003)
1790
>65
CSHA
1-3
Ganguli (2004)
1248
>65
MoVIES
3-4

16. Clinical Spectrum
• 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

17. Classification of MCI
MCI
Amnestic
Single domain
Multiple domain
Non-amnestic
Single domain
Multiple domain

18. Clinical subtypes of mild cognitive impairment

19. Flow chart of decision process for making
diagnosis of subtypes of MCI
Journal of Internal Medicine
Vol 256 Issue 3 Page 183, Sep2004

20. Exclusion of systemic or brain diseases that can cause
cognitive decline
 Depression
- Memory function may improve with
treatment of depression
 Metabolic disturbance
- Memory function may improve if corrected
 Traumatic injury
- Memory function often stabilizes after a
period of recovery
 Vascular disease
- Memory function may stabilize or progress

21. Cognitive Decline
Outcome of MCI
MCI
AD
Age

22. Outcome
The annual rate of
conversion to AD
10 – 15% per year

23. Conversion to AD
Normal
MCI Amnestic Type
Function
Point of conversion
Probable AD
Definite AD
Age

24. 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

25. Mild Cognitive Impairment
(MCI)
MCI →AD 12%/yr
Control→AD 1-2%/yr
100
100
90
90
80
80
70
70
60
60
50
50
Initial
exam
12
24
36
Months
48
Initial
exam
12
24
36
Months
48
Petersen RC et al: Arch Neurol 56:303-308, 1999

26. Outcome
Clinical severity
Type; multiple domain vs single
domain
Genetics: Apolipoprtein E-4 carrier
Biomarkers
Radiological
CSF

27. 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

28. Neuroimaging
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

29. Arrow highlights the body of the
hippocampus. Image on right is from a
patient with atrophy.

30. Arrows mark the entorhinal cortex on MRI.

31. (CSF) biomarkers
• Invasive procedure
• Lack of normative data no
change of these CSF
markers with age
• Effect of drugs on change
in CSF markers

32. (CSF) biomarkers
3 cerebrospinal fluid (CSF)
biomarkers
- total-tau (T- )
- phospho-tau (P- )
- 42 amino acid form of βamyloid (Aβ42)

33. TREATMENT

34. Treatment
• Dopenzil-Vit E-Placebo study
2005
• Galantamine trial; 2004
• Rivastigmine trial; 2004
• Rofecoxib trial; 2005
• Ginko biloba; 2008
• Folic acid vitamin B12 trial; 2004
• Lithium; some benefit 2011
Fail to show any benefit

35. What to do?
• Exercise
• Healthy food
• Cognitive stimulating activities
• Stop smoking
• Control; DM, HTN, Dyslipedemia
• Treat depression

36. Tying it all together!

MCI is a widely
accepted term for
diagnosis of memory
impairment not
fulfilling the criteria of
dementia

Diagnostic criteria
need to be
standardized, to
include it in the
current
classifications.

37. Tying it all together!

Biomarkers are the
main focus of
research now

Current treatment
options are control of
risk factors and
healthy lifestyle