Alzheimer’s Disease

Question 1

Alzheimers Pathology

Answer 1

APP(Amyloid protein precursor). —> B secretase—-> Beta product

G-secretase + Beta product = AB42 + AB40

AB42 (bad)—amyloidogenic protein—misfolds—> NFT + SNP

NFT = intracellular, no. correlates c severity

SNP= Extracellular, no. correlates c age

SNPs—-> sits on Brain BV—CEREBRAL AMYLOID ANGIOPATHY

A product and AB40= non toxic

Question 2

Role of Tau protein in pathogenesis of AD

Answer 2

Tau proteins are neuroprotective—stabilize the microtubules

In AD they get hyper po4—lt NEURODG.

Question 3

Genetic mutations responsible for AD

Answer 3

Chr 21, 14 , 1 , 19

a) 21
- Extra APP gene
- If downs live >40y—Very high risk AD

b) 14
- PRE-SENELIN 1 (PS1)
- Increases G secretase activity
- MCC of EARLY ONSET AD (45y)
- Duration 6-7 y
- Most severe form

c) 1
- PRESENELIN 2 (PS2)
- onset 53 y
- duration 11 y

d) 19
- APOE4 gene
- Avoids clearance of Amyloid protein

Question 4

Factors decreasing risk of AD

Answer 4

NSAIDS

APOE2***

SMOKING

Ability to use complex language in adulthood

Question 5

Factors increasing risk of AD

Answer 5

F/H/o AD inheritance
ApoE4
Female
Age > 70
Al, Hg
BOXER
DM, HTN

ELEVATED HOMOCYSTEINE (Hypercoag)
Decreased fruits veggies

Question 6

C/f of AD

6 A

Answer 6

Earliest - Atrophy of HIPPOCAMPUS
(Long term memory loss- ‘A’mnesia)

TEMPORAL LOBE ATROPHY
-Enterorhinal cortex
-Perirhinal cortex
(‘A’nosmia)

PARIETAL LOBE ATROPHY
-‘A’praxia

ATROPHY OF ASSOC AREAS OF NEOCORTEX

• ‘A’phasia
• ‘A’nosognosia (unaware of disease)

‘A’SPIRATION PNEUMONIA (mccd)

Question 7

Non cognitive symptoms of AD

Answer 7

Positive- Irritability Agitation

Negative- Depression Apathy

Psychotic- Delusion

Question 8

Diagnosis of AD

Answer 8

AcH= DECREASED

Grading- CDS SCALE (Clinical dementia grading)

Bx- 1)NFT

   2) SNP
   3) CAA
   4) Granulo-vacuolar Degeneration

Question 9

Types of APRAXIA (ref notebook for expl)

SIBIL

Answer 9

Complex Motor Deficit NOT attributable to Pyramidal/EP/ Cerebellor/ Sensory dysfunction

Speech

Ideomotor

Buccofacial

Ideational

Limb kinetic

Question 10

Large vessel CAA name and types

C2AF

Answer 10

CORTICAL DEMENTIA

AD

FTD

CJD Dementia

Chronic SDH Dementia

Question 11

Small vessel Dementia name and types

PHPHM

Answer 11

SUB CORTICAL DEMENTIA

PSP

HIV Dementia

PD

Huntingtons

MS

Question 12

Examples of mixed Dementias

Answer 12

VASCULAR DEMENTIA

Question 13

Rx AD

Answer 13

1)AchE inhibitors

RIVASTIGMINE
DONEPEZIL

Prevent degeneration of NUCLEUS BASALIS MYERDENET (Ach)

2) NMDA inhibitors

MEMANTINE

Question 14

FTD other name

Answer 14

PICKS DISEASE

Question 15

Age and sex of FTD and inheritance

Answer 15

AD (10%)

50-60 m>f

> 65 f>m

Question 16

Mutations in FTD

Answer 16

Chr 9 (mc) - C9ORF72 gene

GGGGCC hexanucleotide repeat

Chr 17- MAPT gene

Question 17

What happens in FTD

Answer 17

Frontal/ Temporal lobe are atrophied

localized atrophy

Question 18

Clinical types of FTD and it c/f and lesion location

BSN

Answer 18

BEHAVIOURAL Variant (mc)

• Apathy, Disinhibition (Psycho symptoms)
• Medial and Orbital areas of Frontal L

SEMANTIC Variant

• Cannot decode words/ obj names
• Temporal lobe

NONFLUENT/Agrammatic variant

• Inability to produce a word
• Frontal lobe

Question 19

AD vs FTD

Answer 19

Amnesia+++. +

Apraxia+. -

Ach dec. n

Question 20

Primary Progressive aphasia types

SAL

Answer 20

Semantic- Wernickes
Agrammatic- Brocas
Logopenic- Conduction