Lecture 2

Question 1

What is dementia and AD?

Answer 1

 problem-solving or language.
 Gradual onset & progressive
 AD is the commonest cause of dementia but not all dementia is due to AD.

Question 2

Alois Alzheimer - 1906

Answer 2

 Post-mortem: the cerebral cortex was thinner and senile plaque, previously only encountered in elderly people, were found along with neurofibrillary tangles.

Question 3

Alzheimers Pathology

Answer 3

Amyloid Plaques around neuronal bodies

Question 4

Test for plaques

Answer 4

A) Plaque evident on routine H&E stained section of frontal cortex;
(B) tangle in a hippocampal pyramidal neuron on routine H&E stained section;
(D) immunohistochemistry against Aβ highlights plaques;
(E) immunohistochemistry against tau highlights tangles;

Question 5

 Pathology overlap

Answer 5

 25% of all patients with AD develop parkinsonism.
 50% of all cases of PD develop AD-type dementia after 65 years of age (Hansen et al. 1990).
 70% of patients with sporadic AD display Parkinson’s pathology (Lippa et al. 1998; Trojanowski et al. 1998; Hamilton 2000

Question 6

 NINCDS– ADRDA criteria -1984

Answer 6

 (1) the clinical diagnosis of AD could only be designated as “probable” while the patient was alive and could not be made definitively until AD confirmed at PM
 (2) the clinical diagnosis of AD could be assigned only when the disease had advanced to the point of causing significant functional disability and met the threshold criterion of dementia.

Question 7

Psychiatric changes in AD

Answer 7

 Subtle behaviour changes: inattentiveness, mild cognitive dulling, social withdrawal, emotional withdrawal and agitation
 Apathy (most freq change), disengagement
 Psychotic symptoms: delusions (delusions of theft) or hallucinations
 Agitation, anxiety.

Question 8

Specific clinical phenotype

Answer 8

 Presence of an early and significant episodic memory impairment (isolated or associated with other cognitive or behavioural changes that are suggestive of a mild cognitive impairment that includes the following features:
 Gradual and progressive change in memory function reported by patient or informant over more than 6 months
 Objective evidence of an amnestic syndrome of the hippocampal type,* based on significantly impaired performance on an episodic memory test with established specificity for AD, such as cued recall with control of encoding test

Question 9

In vivo evidence of AD Pathology

Answer 9

 Decreased Aβ1–42 together with increased T-tau or P-tau in CSF
 Increased tracer retention on amyloid PET
 AD autosomal dominant mutation present (in PSEN1, PSEN2, or APP)

Question 10

AD affects what brain regions

Answer 10

Early degenrationof medial temporal lobe before degeneration spreads to temporal neocortex, frontal and parietal association areas.

Question 11

Cognitive Profile in AD

Answer 11

 Episodic memory: frequent intrusions and repetition errors, and high numbers of false positive errors in recall
 Complex attention/executive function
 Disproportionate impairment of category fluency as compared to phonemic fluency

Question 12

Differentials

Answer 12

 Vascular/Mixed Dementia
 Sub-cortical-frontal pattern (attention difficulties, motor/cognitive slowing and executive problems) and visuo-spatial difficulties
 Dementia with Lewy Bodies
 Fluctuating cognition, pronounced disturbances in attention and concentration, working memory and early visuoperceptual deficits, visual hallucinations and spontaneous Parkinsonism
 Depressive pseudo dementia

Question 13

Sub-types of dementia

Answer 13

 Alzheimer’s disease (AD) - 62%
 Vascular dementia (VaD) - 17%
 Mixed dementia (AD & VaD) - 10%
 Dementia with Lewy Bodies (DLB) - 4%
 Fronto-temporal lobe dementias - 2%
 Parkinson’s dementia - 2%
 Other types - 3%

Question 14

Non- memory dysfunction in AD

Answer 14

(I) Apraxia / visuospatial dysfunction 12%:
(II) Language dysfunction- 9%
(III) Aphasic-apraxic-agnosic syndrome
(IV) Posterior cortical atrophy (PCA- 1%):
(V) Dysexecutive syndrome- 2

Question 15

(I) Apraxia / visuospatial dysfunction 12%:

Answer 15

difficulties in spatial orientation, resulting in getting lost
(II) or problems in praxis, for example dressing apraxia

Question 16

(III) Aphasic-apraxic-agnosic syndrome-

Answer 16

%: Combination of language impairment, dyspraxia and agnosia and often mild memory impairment.

Question 17

(IV) Posterior cortical atrophy

Answer 17

Progressive vision problems in reading, visual agnosia or components of Balint syndrome (ocular apraxia, simultanagnosia, optic apraxia)

Question 18

(V) Dysexecutive syndrome

Answer 18

Prominent executive dysfunction with or without behavioural change

Question 19

Preclinical AD (“amnesic prodrome”): MCI

Answer 19

 Memory impairment is first cognitive marker of AD
 Poor performance on episodic memory tests (new learning and retention)
 General cognitive function is preserved, activities of daily living are intact and there is no evidence of dementia
 Score above 24/30 on the MMSE
 High risk for developing AD

Question 20

Medication –

Answer 20

 Acetyl choline esterase inhibitors

 Memantine (anti-glutamate)

Question 21

 Diagnostic tests:

Answer 21

 Structure (MRI or CT)

 Pathology- non-invasive (amyloid & tau imaging)

Question 22

Vascular/Mixed Dementia

Answer 22

Sub-cortical-frontal pattern (attention difficulties, motor/cognitive slowing and executive problems) and visuo-spatial difficulties

Question 23

Dementia with Lewy Bodies

Answer 23

Fluctuating cognition, pronounced disturbances in attention and concentration, working memory and early visuoperceptual deficits, visual hallucinations and spontaneous Parkinsonism