VASCULAR DEMENTIA (VaD)
A BRIEF REVIEW WITH SPECIAL
EMPHASIS ON CURRENT
CLINICAL IMPACT
MURRAY FLASTER MD, PhD
BARROW NEUROLOGICAL CLINIC
OVERVIEW
• HISTORICAL PERSPECTIVE
• PATHOPHYSIOLOGIC BASIS
• CLINICAL IMPACT
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OTTO BINSWANGER 1894
ALOIS ALZHEIMER 1895, 1907
PIERRE MARIE 1901
EMIL KRAEPELIN 1910
C MILLER FISHER 1968
VC HACHINSKI 1974
HACHINSKI ISCHEMIA SCALE
• FEATURE
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ABRUPT ONSET
STEPWISE DETERIORATION
FLUCTUATING COURSE
NOCTURNAL CONFUSION
RELATIVE PRESERVATION OF PERSONALITY
DEPRESSION
SOMATIC COMPLAINTS
EMOTIONAL INCONTINENCE
HISTORY/PRESENCE OF HYPERTENSION
HISTORY OF STROKES
EVIDENCE OF ARTHEROSCLEROSIS
FOCAL NEUROLOGICAL SYMPTOMS
FOCAL NEUROLOGICAL SIGNS
VALUE
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SCORES OVER 7 SUGGEST A VASCULAR ETIOLOGY
In summary:
• Both diffuse and discrete ischemic brain pathological
change and their impact on cognitive function were
recognized by the turn of the last century.
• In the first seven decades of the 20th century, ischemia
both chronic and acute was thought responsible for the vast
majority of dementia cases.
• A cellular basis for dementia was increasingly recognized
in the later half of the 20th century, while vascular
dementia was recognized primarily in the restricted form
of multi-infarct dementia.
• Today, vascular dementia is recognized as a heterogeneous
group of disorders, each with its own pathophysiologic
characteristics. Any of these processes can contribute to a
dementing illness, and any could in theory overlap with a
cellular dementia.
AD
Va D
OTHER CELLULAR
AND TISSUE DEMENTIAS
A little epidemiology
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ALL DEMENTIAS
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ALZHEIMER’S DISEASE
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PREVALENCE OF “PURE” VASCULAR DEMENTIA 10 - 19% IN US AND WESTERN
COUNTRIES IN GENERAL, BUT PERHAPS DOUBLE THAT RATE IN JAPAN AND
CHINA. MIXED DEMENTIAS INCLUDING A VASCULAR COMPONENT MAY RANGE
FROM 10 TO 40% OF ALL DEMENTIAS.
SUBCORTICAL VASCULAR DEMENTIA
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UP TO 90% OF ALL DEMENTIA CASES INCLUDE SOME SIGNIFICANT DEGREE OF
ALZHEIMER’S PATHOLOGY AND CLINICAL ATTRIBUTES. “PURE” ALZHEIMER’S
CASES COMPRISE UP TO 2/3rds OF THAT TOTAL.
VASCULAR DEMENTIAS
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PREVALENCE OF 1% AT AGE 60; AND DOUBLES EVERY FIVE YEARS, REACHING
32% BY AGE 85.
NO GOOD STATISTICS AVAILABLE, PERHAPS 4% OF ALL DEMENTIAS HAVE SOME
DEGREE OF SUBCORTICAL VASCULAR DEMENTIA, PERHAPS LESS THAN 1% OF
VASCULAR DEMENTIA MEET CRITERIA FOR “PURE” BINSWANGER’S DISEASE.
OVERALL, ALZHEIMER’S DISEASE IS IMPLICATED IN NEARLY 90% OF ALL
DEMENTIA CASES, WHILE VASCULAR DEMENTIA AND LEWY BODY
DISEASE REPRESENT THE SECOND AND THIRD MOST IMPORTANT
CONTRIBUTORS TO THE TOTAL BURDEN OF DISEASE.
AD
Va D
OTHER CELLULAR
AND TISSUE DEMENTIAS
US, CANADA, WESTERN EUROPE
AD
Va D
OTHER CELLULAR
AND TISSUE DEMENTIAS
JAPAN AND CHINA
NOSOLOGY
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CELLULAR/MOLECULAR
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ALZHMEIMER’S DISEASE (BAMYLOID )
– DIFFUSE LEWY BODY
DISEASE (SYNUCLEIN ?)
– FRONTO-TEMPORAL
DEMENTIAS , PSP (TAU ?)
– OTHERS ( MITOCHONDRIAL
DISEASES, HEREDITARY
PRION DISEASE, WILSON’S
DISEASE, ETC.)
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TISSUE/ORGAN/SYSTEMIC
– NORMAL PRESSURE
HYDROCEPALUS
– INFECTION (SYPHILIS, HIV,
HTLVIII, CJD, WHIPPLE’S
ETC.)
– INFLAMMATION (MS,
PARANEOPLASTIC,ETC.)
– HYPOXIC/METABOLIC/TOXIC
(GLOBAL ISCHEMIA, B12
DEFICIENCY ETC.)
– VASCULAR DEMENTIAS
VASCULAR DEMENTIAS
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LARGER ARTERY SYNDROMES (MULTI-INFARCT DEMENTIA)
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CARDIAC, CAROTID, VERTEBRAL OR INTRACRANIAL ATHEROSCLEROTIC
DISEASE.
CORTICAL INFARCTS, LARGER SUBCORTICAL INFARCTS ( AS MIGHT BE SEEN IN
M1 OCCLUSIONS ).
RISK FACTORS/MECHANISMS ARE NUMEROUS: HYPERTENSION,
HYPERLIPIDEMIA,TOBACCO SMOKE, DIABETES, CORONARY ARTERY, DISEASE
ATRIAL FIBRILLATION, CARDIOMYOPATHY, VALVULAR DISEASE, PARADOXIC
EMBOLISM.
SMALL VESSEL SYNDROMES ( SUBCORTICAL DEMENTIA )
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BINSWANGER SYNDROME
LACUNAR STATE ( WITH OR WITHOUT SUBCORTICAL HEMORRHAGES ).
RISK FACTORS: HYPERTENSION, DIABETES, HYPERLIPIDEMIA, TOBACCO
SMOKE.
– VASCULITIDES (ISOLATED CNS, SYSTEMIC, ANTI-CARDIOLIPIN,
MICROANGIOPATHIES SUCH AS TTP)
– CADASIL, (AND NOW CARASIL)
STRATEGIC INFARCT DEMENTIA ( THALAMUS, PCA INARCTION INVOLVING
TEMPORAL LOBE, ANTERIOR LIMB OF INTERNAL CAPSULE ETC.)
HEMORRHAGIC DEMENTIAS ( SUBARACHNOID HEMORRHAGE, SUBDURAL
HEMORRAGE, RECURRENT LOBAR HEMORRHAGE ).
– `CEREBRAL AMYLOID SYNDROMES (DUTCH, BRITISH, ICELANDIC) WITH
HEMMORRHAGE AND ISCHEMIA.
BOLD LETTERING INDICATES CLASS I AND/OR CLASS II SUPPORT
AD
Va D
OTHER CELLULAR
AND TISSUE DEMENTIAS
How do you differentiate these clinically?
How do you separate pure from mixed forms
for clinical or study purposes?
Do these diseases/processes interact?
SEPARATING VASCULAR DEMENTIA FROM ALZHEIMER’S
DISEASE IN THE ABSENCE OF CLINICALLY OBVIOUS
INFARCTIONS
• Va D
– LESS MEMORY LOSS
EARLY ON
– GAIT ABNORMALITIES
EARLY ON
– RIGIDITY EARLY ON
– DYSARTHRIA
– EXECUTIVE
DYSFUNCTION AND
OTHER “FRONTAL LOBE “
BEHAVIORAL CHANGES
OUTPACE MEMORY LOSS
• AD
– MEMORY IMPAIRMENT
PREDOMINATES EARLY
ON
– POOR LEARNING
– APHASIA WITH ANOMIA
FOR DETAIL
– LACK OF MOTOR
ABNORMALITIES ON
NEUROLOGIC EXAM
UNTIL RELATIVELY LATE
IN THE DISEASE PROCESS
THERE REMAINS AN OVERLAP BETWEEN DEMENTIA
SYNDROMES CLINICALLY AND AN OVERLAP IN
RISK FACTORS AND TREATMENT.
• HYPERTENSION AND ANTIHYPERTENSIVE
THERAPY
• HYPERLIPIDEMIA AND STATIN THERAPY
• ANTI-CHOLINERGIC THERAPY
• ATRIAL FIBRILLATION
HYPERTENSION
• METAANALYSIS OF NINE CLASS I STUDIES ( GUEYFFIER et al
1997) SHOWED ANTI-HYPERTENSIVES REDUCED THE
INCIDENCE OF RECURRENT STROKE BY 28%.
• THE EFFICACY OF ANTIHYPERTENSIVES INPRIMARY
STROKE PREVENTION IS ALSO WELL ESTABLISHED.
STROKE RISK CAN BE REDUCED BY 40%.
• MORE LIMITED DATA ( SMALL TRIALS AND POPULATION
STUDIES ) SUPPORT THE NOTION THAT BLOOD PRESSURE
CONTROL REDUCES DEMENTIA INCIDENCE ( BUT THIS
RELATIONSHIP MAY BE COMPLEX ).
HYPERLIPIDEMIA AND STATINS
• STATINS (HMG CO-A INHIBITORS) REDUCE
STROKE RISK BY UP TO 30% (PRAVASTATIN IN
CARE TRIAL AMONG OTHERS).
• POPULATION STUDIES SUGGEST STATINS MAY
ALSO REDUCE THE INCIDENCE OF DEMENTIA
(PRESUMEABLY AD).
• (MORE STUDY IS NEEDED)
ANTI-CHOLINERGICS AND VaD
• BOTH DONEPEZIL (ARICEPT) AND GALANTAMINE
(REMINYL) HAVE SHOWN EFFICACY IN PLACEBO
CONTROLLED TRIALS OF DEMENTIA PATIENTS WITH A
SIGNIFICANT VASCULAR DEMENTIA COMPONENT.
• RIVASTIGMINE (EXELON) MAY ALSO BENEFIT IN A SIMILAR
POPULATION.
• THE SIGNIFICANCE OF THE OVERLAP IN EFFICACY IN BOTH
VaD AND ALZHEIMER’S DISEASE PATIENTS COULD REFLECT
EITHER A COMMON VASCULAR CHOLINERGIC EFFECT, A
COMMON CELLULAR DEFICIENCY BUT PROBABLY NOT
INADEQUATE SEPARATION OF DEMENTIA SUBTYPES.