demensia vaskuler
TRANSCRIPT
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
• OTTO BINSWANGER 1894
• ALOIS ALZHEIMER 1895, 1907
• PIERRE MARIE 1901
• EMIL KRAEPELIN 1910
• C MILLER FISHER 1968
• VC HACHINSKI 1974
HACHINSKI ISCHEMIA SCALE
• FEATURE VALUE– ABRUPT ONSET 2
– STEPWISE DETERIORATION 1
– FLUCTUATING COURSE 2
– NOCTURNAL CONFUSION 1
– RELATIVE PRESERVATION OF PERSONALITY 1
– DEPRESSION 1
– SOMATIC COMPLAINTS 1
– EMOTIONAL INCONTINENCE 1
– HISTORY/PRESENCE OF HYPERTENSION 1
– HISTORY OF STROKES 2
– EVIDENCE OF ARTHEROSCLEROSIS 1
– FOCAL NEUROLOGICAL SYMPTOMS 2
– FOCAL NEUROLOGICAL SIGNS 2
• 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.
Va D
AD
OTHER CELLULARAND TISSUE DEMENTIAS
A little epidemiology• ALL DEMENTIAS
– PREVALENCE OF 1% AT AGE 60; AND DOUBLES EVERY FIVE YEARS, REACHING 32% BY AGE 85.
• ALZHEIMER’S DISEASE– 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– 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– 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.
Va D
AD
OTHER CELLULARAND TISSUE DEMENTIAS
US, CANADA, WESTERN EUROPE
Va D
AD
OTHER CELLULARAND TISSUE DEMENTIAS
JAPAN AND CHINA
NOSOLOGY
• CELLULAR/MOLECULAR– ALZHMEIMER’S DISEASE (B-
AMYLOID )
– DIFFUSE LEWY BODY DISEASE (SYNUCLEIN ?)
– FRONTO-TEMPORAL DEMENTIAS , PSP (TAU ?)
– OTHERS ( MITOCHONDRIAL DISEASES, HEREDITARY PRION DISEASE, WILSON’S DISEASE, ETC.)
• 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• LARGER ARTERY SYNDROMES (MULTI-INFARCT DEMENTIA)
– 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 )– 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
Va D
AD
OTHER CELLULARAND TISSUE DEMENTIAS
How do you differentiate these clinically?How do you separate pure from mixed formsfor 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
• A D– 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.