Slides 1-2

INTERACTION OF VASCULAR FACTORS
AND ALZHEIMER'S DISEASE

Ingmar Skoog, M.D., Ph.D.
Research Group for Neuropsychiatric Epidemiology

Alzheimer's Disease

Degeneration of specific nerve cells
Accumulation of the beta-amyloid peptide
Senile plaques
Neurofibrillary tangle
Cerebral amyloid angiopathy

Slide 3

CRITERIA FOR ALZHEIMER'S DISEASE (NINCDS-ADRDA)

Probable AD:
progressive worsening of dementia

Possible AD:
presence of a neurologic, psychiatric or systemic disorder sufficient
to produce dementia but not considered to be the cause of the dementia;
variations in the onset, presentation or in the clinical course

Other Causes:
Temporal connection with a neurolgoic, psychiatric or systemic disorder
sufficient to produce and considered to be the cause of the dementia

Slide 4

RISK FACTORS FOR ALZHEIMER'S DISEASE

Old age
Down's syndrome
Family history of dementia
ApoE genotype
Low education
Female sex
Vascular risk factors
Head trauma
Thyroid disease
Family history of Down's syndrome
Psychological stress
Previous depression

Slide 5

VASCULAR RISK FACTORS IN ALZHEIMER'S DISEASE

Hypertension
ApoE e4 allele
Generalized atherosclerosis
Coronary heart disease
Changes in cardiac innervation
Atrial fibrillation
Diabetes mellitus
Stroke
Ischemic white matter lesions
Changes in cerebral microvessels

Skoog 1997

Slide 6

Slide 7

BLOOD PRESSURE IN ALZHEIMER'S DISEASE

Increased before onset

Lower after onset

Slide 8

DENSITY OF SENILE PLAQUES
IN PARAHIPPOCAMPAL GYRUS

Sparks et al.
J. Neurol Sci 1995; 131:162-169

Slide 9

DENSITY OF NEUROFIBRILLARY TANGLES
IN PARAHIPPOCAMPAL GYRUS

Sparks et al.
J. Neurol Sci 1995; 131:162-169

Slide 10

VASCULAR RISK FACTORS IN ALZHEIMER'S DISEASE

Hypertension
ApoE e4 allele
Generalized atherosclerosis
Coronary heart disease
Changes in cardiac innervation
Atrial fibrillation
Diabetes mellitus
Stroke
Ischemic white matter lesions
Changes in cerebral microvessels

Skoog 1997

Slide 11

APOLIPOPROTEIN E (ApoE)

Three different alleles (Apo e2, e3, e4)
Three isoforms (ApoE2, E3, E4)
Six different phenotypes

ApoE4 associated with:

Cholesterol
LDL
Coronary heart disease
Atherosclerosis
Alzheimer's disease

Slide 12

SERUM CHOLESTEROL 1959-75
IN RELATION TO ALZHEIKMER'S DISEASE 1989

Adjusted for ApoE e4 allele
Notkola et al. Neuroepidemiologi 1998; 17:14-20

Slide 13

VASCULAR RISK FACTORS IN ALZHEIMER'S DISEASE

Hypertension
ApoE e4 allele
Generalized atherosclerosis
Coronary heart disease
Changes in cardiac innervation
Atrial fibrillation
Diabetes mellitus
Stroke
Ischemic white matter lesions
Changes in cerebral microvessels

Skoog 1997

Slide 14

Slide 15

VASCULAR RISK FACTORS IN ALZHEIMER'S DISEASE

Hypertension
ApoE e4 allele
Generalized atherosclerosis
Coronary heart disease
Changes in cardiac innervation
Atrial fibrillation
Diabetes mellitus
Stroke
Ischemic white matter lesions
Changes in cerebral microvessels

Skoog 1997

Slide 16

CORONARY HEART DISEASE AND ALZHEIMER'S

• Increased incidence of AD in women with
  myocardial infarction
  Aronson et al, Neurology 1990
• Increased amounts of cortical senile plaques
  in individuals with coronary heart disease
  Sparks et al, Neurobiol Aging 1990
  Soneira et al, Clinical Anatomy 1996

Slide 17

VASCULAR RISK FACTORS IN ALZHEIMER'S DISEASE

Hypertension
ApoE e4 allele
Generalized atherosclerosis
Coronary heart disease
Changes in cardiac innervation
Atrial fibrillation
Diabetes mellitus
Stroke
Ischemic white matter lesions
Changes in cerebral microvessels

Skoog 1997

Slide 18

CARDIAC INNERVATION IN ALZHEIMER'S DISEASE

Increased sympathetic innervation

Decreased parasympathetic innervation

Slide 19

A RELATIVELY HYPERSYMPATHETIC
HYPOPARASYMPATHETIC STATE

Early Alzheimer's disease

Early hypertension

Slide 20a-b

VASCULAR RISK FACTORS IN ALZHEIMER'S DISEASE

Hypertension
ApoE e4 allele
Generalized atherosclerosis
Coronary heart disease
Changes in cardiac innervation
Atrial fibrillation
Diabetes mellitus
Stroke
Ischemic white matter lesions
Changes in cerebral microvessels

Skoog 1997

Slide 21

ATRIAL FIBRILLATION AND ALZHEIMER'S DISEASE

Ott et al.
Stroke 1997; 28:316-321

Slide 22

VASCULAR RISK FACTORS IN ALZHEIMER'S DISEASE

Hypertension
ApoE e4 allele
Generalized atherosclerosis
Coronary heart disease
Changes in cardiac innervation
Atrial fibrillation
Diabetes mellitus
Stroke
Ischemic white matter lesions
Changes in cerebral microvessels

Skoog 1997

Slide 23

DIABETES MELLITUS AND ALZHEIMER'S DISEASE

Diabetes mellitus
Ott et al. Rotterdam Study
Diabetologia 1996; 39:1392-1397

Leibson et al. Rochester
Am J Epidemiol 1997; 145:301-308

Insulin resistance syndrome
Kuusisto et al. Kuopio
Brit Med J 1997; 315:1045-1049

Slide 24

VASCULAR RISK FACTORS IN ALZHEIMER'S DISEASE

Hypertension
ApoE e4 allele
Generalized atherosclerosis
Coronary heart disease
Changes in cardiac innervation
Atrial fibrillation
Diabetes mellitus
Stroke
Ischemic white matter lesions
Changes in cerebral microvessels

Skoog 1997

Slide 25-28

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