PDD and LBD

Question 1

What is the pathophysiology of PDD?

Answer 1

Alpha synucleinopathy

Question 2

What are the risk factors for PDD?

Answer 2

1. Advanced age
2. Severity of motor symptoms
3. Duration of illness
   Other
4. Depression
5. Hallucinations
6. Atypical sx (early OH, symmetrical Parkinsonism, partial response to Ldopa)
7. REM disorder

Question 3

What are the cognitive and behavioural features of PDD?

Answer 3

Cognitive
1. Memory (free recall)
2. Attention
3. Executive
4. VS
Behavioural
1. Affective (depression or anxiety)
2. Hallucinations
3. Apathy
4. Delusions
5. Excessive daytime sleepiness

Question 4

Treatment of PDD

Answer 4

1. Reassess meds: anticholinergics, amantadine, TCA, tolterodine, oxybutynin, sedatives
2. Cognitive enhancers
   a. Rivastigmine - improve cognition, function, behaviours, worsens tremors, N/V
   b. Donepezil - at 10 mg, global change
   c. Galantamine (grade C)
   d. Memantine - adjunct or second line mono therapy
3. BPSD
   a. Pimavanserin - dec hall/del
   b. Antipsychotics - quetiapine only
   c. Naltrexone - impulse control disorders

Question 5

What is the pathophysiology of LBD?

Answer 5

Alpha synucleinopathy
Lewy bodies - inclusion bodies, made of alpha synuclein, ubiquitin and p62
Lewy neurites - elongated, beaded nerve processes alpha synuclein
Amyloid plaque - 80% LBD have concomitant AD changes

Question 6

What are the core features of LBD?

Answer 6

1. Fluctuating cognition - variations in attention and alertness
2. Recurrent VH - well formed, detailed
3. REM SBD (may precede cog)
4. 1+ sx of Parkinsonism (rest tremor, bradykinesia, rigidity)

Question 7

Supportive features of LBD

Answer 7

Sensitive to psychotropic drugs
Postural instability
Repeat falls
Syncope
Sev autonomic dysfunction
Hypersomnia
Hyposmia
Mood disturbances
Delusions

Question 8

LBD biomarkers

Answer 8

Indicative
1. Dec dopamine transporter uptake in basal ganglia
2. Dec uptake iodine on MIBG myocardial scintigraphy
3. REM sleep without atonia on sleep study
Supportive
1. Preserved medial temporal lobe
2. Dec uptake on SPECT/PET with dec occipital acitivty
3. Posterior slow wave activity on EEG

Question 9

LBD treatment of extrapyramidal symptoms

Answer 9

Variable response to dopaminergic agents
Can try L dopa but inc risk hallucinations

Question 10

LBD treatment of cognitive impairment

Answer 10

CHEI - rivastigmine and donepezil
Improve cognition, global function and ADLs
Memantine efficacy less clear

Question 11

LBD treatment of BPSD

Answer 11

Non Pharm
1. Rule out underlying medical cause
2. Reduce/eliminate psychoactive medications
3. Reduced PD meds as tolerated (anticholinergic, amantadine, DA, MAO-B, COMT, Ldopa)
Pharm
3. CHEI - rivastigmine for hallucinations, delusion, apathy and anxiety
4. Quetiapine or pimavanserin
5. Clozapine

Question 12

How to differentiate LBD vs. PDD?

Answer 12

Depends on timeline of CI and parkinsonism
LBD - <1 year between onset
PDD - >1 year, usually Parkinsonism then CI

Symmetry - symmetrical and no tremors vs. asymmetric and tremors
Ldopa - mixed response vs. good
VH - early and complex, later and complex
Onset - 75 yo vs. younger
Evolution - 7-10 yrs vs. 15-20 yrs

Question 13

Ddx for LBD

Answer 13

1. PDD
2. PSP
3. Vascular
4. Advanced AD

Question 14

What are reasons to avoid neuroleptics in patients with LBD?

Answer 14

Dopamine blockade resulting in:
1. Neuroleptic hypersensitivity rxn
2. Rigidity
3. Worsening cognition/delirium
4. NMS
5. Worsening EPS, Parkinsonism