Neuropathology of Dementia

Question 1

What is Dementia ?/

Answer 1

• Multiple cognitive defects, including memory impairment
• Impairs occupational or social functioning
• Represents a decline from a previously high level of functioning
• Absence of delerium or depression
• Mild cognitive impairment (MCI)

Question 2

Mild Cognitive Impairment

Answer 2

• Cognitive impairment on testing
• Daily functioning preserved
• 15% of MCI patients deteriorate to AD per year

Question 3

What do dementia syndromes depend on ?

Answer 3

Anatomical region affected

Question 4

• Temporo-parietal

Answer 4

e.g. Alzheimer’s disease) • Early memory symptoms

Question 5

Fronto-temporal

Answer 5

e.g. Frontotemporal dementias) • Executive functions, behaviour, language disturbance

Question 6

subcortical

Answer 6

eg. Vascular dementia

• Reduced speed and efficiency of cognition

Question 7

What is the biggest risk factor for dementia ??

Answer 7

Age

Question 8

Causes of dementia - not all neurodegenerative

Answer 8

Neurodegenerative Diseases • Alzheimers
• Dementia with Lewy Bodies • Picks Disease
• MND inclusion dementia
• FTDP-17
• Dementia lacking distinctive histology • Progressive supranuclear palsy
• Argyrophilic grain disease
• Corticobasal degeneration
• Huntington’s disease Etc. • Vascular Diseases
• Vascular dementia
• Infectious/Inflammatory/Immune • Prion diseases
• Neurosyphilis, AIDS
• Multiple sclerosis
• Toxic and Metabolic

Question 9

The history of Alzheimers

Answer 9

1907- Auguste D 
Clinical features – 
-	Recent memory 
-	Visuospatial 
-	Language 
-	Attention 
MCI

Question 10

Risk factors of Alzheimers Disease

Answer 10

• Age
• Family history
• Cardiovascular disease
• Diabetes
• Low educational attainment (cognitive reserve hypothesis) • Head injury
• High serum homocysteine

Question 11

Alzheimers Disease Pathology

Answer 11

Cerebral atrophy
• Neurofibrillary tangles
• Plaques – diffuse and neuritic -Cerebral amyloid angiopathy
• Granulovacuolar degeneration - Hirano bodies
• Neuropil threads
• Synaptic loss
• Neuronal loss
• Gliosis / microglial reaction

Question 12

Plaques

Answer 12

Diffuse and neuritic plaques
Extracellular
Contain β-amyloid
Detectable by immunohistochemistry to Aβ and silver stains

Question 13

Neuritic Plaques

Answer 13

surrounded by dystrophic neurites which label with tau

Question 14

Neuritic/compact plaques

Answer 14

have fibrillar Aβ – β-pleated sheet structure detectable by Congo red staining or thioflavine S

Question 15

Neuroanatomical Progression of ABeta

Answer 15

1. Isocortical
2. Allocortical (entorhinal,
   hippocampus, cingulate)
3. Diencephalon and basal ganglia
4. Brainstem
5. Cerebellum

Question 16

Neurofibrillary Tangle

Answer 16

• Intracellular – within neurones
• Found, with plaques, in normal ageing
• Detectable by silver stains or antibodies to abnormally phosphorylated tau protein
• EM – contain paired helical filaments (22nm)
• Distribution in AD is hierarchical

Question 17

Tau deposits

Answer 17

Tau deposits not specific to AD but usually present without Beta amyloid plaques

Question 18

Braak Staging for Neurofibrillary Tangles

Answer 18

Braak staging – 6 stages 
• Entorhinal 
• Limbic
• Neocortical 
•Progression implicit 
•Threshold for dementia not predictable 
•Overlap between demented and non- demented elderly