Professional Documents
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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
FEATURE
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
2 1 2 1 1 1 1 1 1 2 1 2 2
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
A little epidemiology
ALL DEMENTIAS
PREVALENCE OF 1% AT AGE 60; AND DOUBLES EVERY FIVE YEARS, REACHING 32% BY AGE 85. UP TO 90% OF ALL DEMENTIA CASES INCLUDE SOME SIGNIFICANT DEGREE OF ALZHEIMERS PATHOLOGY AND CLINICAL ATTRIBUTES. PURE ALZHEIMERS CASES COMPRISE UP TO 2/3rds OF THAT TOTAL. 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. 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 BINSWANGERS DISEASE.
ALZHEIMERS DISEASE
VASCULAR DEMENTIAS
OVERALL, ALZHEIMERS 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
AD Va D
NOSOLOGY
CELLULAR/MOLECULAR
ALZHMEIMERS DISEASE (BAMYLOID ) DIFFUSE LEWY BODY DISEASE (SYNUCLEIN ?) FRONTO-TEMPORAL DEMENTIAS , PSP (TAU ?) OTHERS ( MITOCHONDRIAL DISEASES, HEREDITARY PRION DISEASE, WILSONS DISEASE, ETC.)
TISSUE/ORGAN/SYSTEMIC
NORMAL PRESSURE HYDROCEPALUS INFECTION (SYPHILIS, HIV, HTLVIII, CJD, WHIPPLES 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.
AD Va D
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 ALZHEIMERS 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 ).
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)
THE SIGNIFICANCE OF THE OVERLAP IN EFFICACY IN BOTH VaD AND ALZHEIMERS DISEASE PATIENTS COULD REFLECT EITHER A COMMON VASCULAR CHOLINERGIC EFFECT, A COMMON CELLULAR DEFICIENCY BUT
PROBABLY NOT INADEQUATE SEPARATION OF DEMENTIA SUBTYPES.