Cognitive

impairment:etiology&pathophysiol
ogy

Cognitive impairment and in the elderly

*cognitive impairment can be defined as any decline in
cognitive ability and subdivided into acute reversible and
chronic irreversible forms ( Marcantonio, 2000)
*A number of epidemiological studies show strong
associations between elevations in middle
life blood pressure and the prevalence of later life cognitive
impairment and dementia(Launer et al 1995, syst-eur 1998)
*cerebrovascular risk factors are associated with
accelerated brain atrophy, abnormalities of cerebral white
matter and silent stroke that could impact on cognitive
performance( Swan GE et al 2000)

High blood pressure precedes the

development of dementia
Non-demented
SBP
mmHg
180

DBP
mmHg
110

170

100

160

90

150

80

140

70
70

75

80

Age (years)

85

70

Onset of Alzheimers
disease after 79
Onset of vascular
dementia after 79

75

80

85

Age (years)
Skoog et al 1996

Cognitive impairment and the

elderly
multiple studies consistently show
significant associations between the
extent of brain atrophy or white matter
hyperintensity (WMH) volumes and
diminished cognitive performance [],
including deficits in tests of attention and
mental processing( DeGroot et al 2000)

Mild Cognitive impairment and

stroke
significant associations between cognitive
impairmentincluding incident dementiaand
clinically silent cerebral infarctions(Vermeer SE
et al 2003)
Mild Cognitive Impairment (MCI) has become
increasingly recognized as common to later life
defined as isolated memory impairment in an
otherwise healthy individual,

Mild cognitive impairment and stroke

individuals over a wide range of cognitive performance from
normal to dementia and found increased volumes of WMH were
associated with cognitive impairment, including memory loss
(Wu et al 2002)
older male veteran twins:memory impairments sufficient for MCI
were found to have significantly greater WMH volumes and
higher blood pressure than subjects with normal memory(Lopez
et al 2003)
strong interaction between evidence of cerebrovascular brain
injury and hippocampal atrophy, increase the likelihood of
clinical dementia(Wu et al 2002)
cerebrovascular disease might accelerate the process by which
individuals transition from MCI to dementia.
(DeCarli 2004)

STROKE AND DEMENTIA

CATEGORY

CLINICAL PRESENTATION

lacunar infarctions

progressive dementia, focal

deficits, or apathetic, frontal-lobelikesyndrome,may have no stroke
history

single strategic infarctions

sudden onset aphasia, agnosia,

anterograde amnesia, frontal lobe
syndrome

multiple infarctions

step-wise appearance of cognitive

& motor deficits

mixed AD-vascular
dementia

progressive dementia with remote

or concurrent history of stroke

white matter infarctions

(Binswanger's disease)

dementia, apathy, agitation,

bilateral cortico-spinal/bulbar signs

Cognitive State and WMH Volume

Wu, et al. Neurology 2003

Effect of WMH + Hippocampal

Atrophy on Dementia Risk
Odds Ratio

Normal Hippocampus, Normal WMH *

Atrophied Hippocampus, Low WMH
Normal Hippocampus,High WMH
Atrophied Hippocampus, High WMH

1.0
14.212
13.028
44.667

95% Confidence Interval

[3.19 63.40]
[2.95 57.56]
[8.43 236.57]

* Reference group

Wu, et al. Neurology 2003

Traditional View of the Dementias

MECHANISM

PATHOLOGY

SYNDROME

Abnormal
APP Metabolism

Senile Plaques
Neurofibrillary Tangles

Alzheimers
Dementia

Cerebral Vascular
Disease

Cerebral Infarction

Vascular
Dementia

Cognitive impairment in STROKE

Mild Cognitive Impairment

Petersen RC

Memory complaint corroborated by

an informant
Normal general cognitive function
Normal activities of daily living
Memory impairment in relation to
age and education
Not demented

Mild Cognitive Impairment

Cognitive Performance
Normal

MCI

Dementia

MCI refers to the state of cognition and

functional ability between normal aging and
very mild AD
(Petersen, 2001)

Pre-dementia syndromes

Age Associated Memory Impairment (AAMI)

Age Related Memory Decline (ARMD)
Age Related Cognitive Decline (ARCD)
Benign Senescent Forgetfulness (BSF)
Cognitive Impairment No Dementia (CIND)
Memory Impairment
Mild Cognitive Disorder (MCD)
Mild Cognitive Impairment (MCI)
Mild Neurocognitive Disorder (MND)
Questionable dementia (QD)

Aging, AAMI (ARCD), MCI, and AD

1 SD

Elderly

Young

Frequency

A
B
AD

MCI AAMI
Cognitive Performance

Adapted from Ferris and Kluger. Aging, Neuropsychology and Cognition, 1996.

Dementia is a Multifactorial
Disorder

INJURY FACTORS

PROTECTIVE FACTORS

Major Mutations
Susceptibility Genes
Head Injury
Depression
Withdrawal of Trophic Factors
Vascular Risk Factors
Et cetera
Neuronal Injury
Functional Impairment
Dementia

Aging

Genetics
Education
Trophic Factors
Anti-hypertensives
Antioxidants
Antiinflamatories
Et cetera
Neuronal Survival
Functional Maintenance
Cognitive Health

Cerebrovascular Risk Factors

and Dementia in SALSA

Prevalence of Diabetes = 32.4 %

OBSERVATIONAL STUDY ON COGNITIVE

FUNCTION IN THE ELDERLY LIVING IN SOME
NURSING HOMES IN JAKARTA 1996

RESULTS:
PROBABLE DEMENTIA WERE NOTED IN 20.7%
OF CASES (MMSE SCORE 0-19) AND PROBABLE
BORDERLINE DEMENTIA IN 10.7%(MMSE SCORE 20-23)
IT WAS ESTIMATED THAT USING HACHINSKI
SCORE, DEMENTIA OF ALZHEIMER-TYPE WERE
31.9% AND VASCULAR DEMENTIA WERE ESTIMATED 55.3%.

Impact of Stroke on Dementia

OR for Dementia
(95th CL)
Present

2.12 (1.06-4.25)

Number
1

1.69 (0.70-4.09)

2+

2.67 (1.08-6.61)

Volume
1st Quartile

0.92 (0.28-3.07)

2nd Quartile

2.31 (0.70-7.64)

3rd Quartile

2.84 (0.85-9.45)

4th Quartile

3.35 (0.95-11.75)

Bennett et al, Neurology 2003

CONCLUSION