Dementia With Lewy Bodies and Parkinson s Disease with Dementia. Morris Freedman MD, FRCPC. Disclosures. Morris Freedman MD, FRCPC

Transcription

1 Dementia With Lewy Bodies and Parkinson s Disease with Dementia Baycrest University of Toronto Research Funding Pfizer, Eli Lilly Disclosures Honoraria for CME Janssen, Novartis, Pfizer, Lundbeck Consulting Janssen, Novartis, Pfizer, Wyeth Dementia with Lewy Bodies Objectives Provide update on criteria for DLB Review cognitive deficits in DLB Contrast cognitive deficits in DLB and AD Describe hallucinations, REM sleep behaviour disorder and fluctuations in DLB Discuss relation between DLB and PDD Review treatment of DLB and PDD

2 Criteria for Probable DLB Dementia plus two of the following Recurrent visual hallucinations Prominent fluctuations Spontaneous features of Parkinsonism McKeith et al. Neurology 65: , 2005 Additional Diagnostic Criteria Suggestive Features REM sleep behavior disorder Severe neuroleptic sensitivity Low DA transporter uptake in basal ganglia on SPECT or PET One or more suggestive features + One or more core features = probable DLB Visual Hallucinations Well-formed People, animals, objects Associated with temporal lobe Lewy bodies Harding et al. Brain 2002 Aarsland et al. J Geriatr Psychiatry Neurol, 2004

3 Case 83 year old physician 3-4 year hx of slight cognitive decline Visual hallucinations Good insight Video Hallucinations Usually Visual Prevalence (%) DLB PDD AD Emre et al. Movement Disorders 2007

4 REM Sleep Behaviour Disorder Loss of muscle paralysis during REM sleep Excessive motor activity when dreaming Video Fluctuations Refer to wide swings in Cognition Attention Alertness Can occur over minutes, hours or days

5 Video Parkinsonism in DLB Seen in 20-25% of cases at diagnosis Supportive Features Include Repeated falls and syncope Transient, unexplained loss of consciousness Severe autonomic dysfunction Hallucinations in other modalities Systematized delusions

6 Cognitive Features in DLB Visuospatial function Memory Attention Language Frontal function Visuospatial Deficits Prominent in DLB Worse compared to AD DLB worse than AD Fragmented letters Object decision Cube analysis MMSE DLB 20.0 AD 21.4 Calderon et al. J Neurol Neurosurg Psychiatry 2001

7 Fragmented Letters DLB worse than AD Fragmented Letters DLB worse than AD State which is a real object Object Decision DLB < AD

8 Copy Free Drawn Case 1 DLB MMSE 27/30

9 Verbal Episodic Memory DLB better than AD Example Immediate and delayed recall (WMS-R) MMSE 20.0 (DLB) and 21.4 (AD) Calderon et al. J Neurol Neurosurg Psychiatry 2001, Visual Episodic Memory DLB may be worse than AD Hard to interpret due to possible confound of poor visuospatial function on testing Metzler-Baddely, Cortex 2007 Anatomical MRI Data Temporal Lobe Atrophy Greater volume loss in AD than DLB Whole temporal lobe Hippocampus Amygdala Barber et al. Neurology, 1999, 2000

10 Semantic Memory Category fluency DLB=AD Calderon et al. J Neurol Neurosurg Psychiatry 2001 Video Attention Prominently affected in DLB

11 Video Bedside Test Frontal Dysfunction Frontal Function DLB worse or equal to AD DLB < AD Establishing set Shifting set DLB=AD Phonemic fluency Similarities Metzler-Baddeley Cortex 2007

12 Cognitive Profile in Early DLB Pronounced deficits in Visuospatial function Attention Frontal function Verbal memory relatively less impaired Relation Between DLB and PDD One-year rule Cognitive profile in PDD similar to DLB PDD and DLB may represent different parts of a spectrum on Lewy body disease Criteria for Probable PDD (paraphrased) Core Features Dx of PD according to specific criteria Dementia syndrome Associated Features At least 2 of impaired attention, executive function, visuospatial function, free recall which usually improves with cueing Emre et al. Movement Disorders 2005

13 Criteria for Probable PDD (paraphrased) Exclusions No features that make dx uncertain, eg relevant vascular disease on imaging and unknown time interval between motor and cognitive symptom onset Emre et al. Movement Disorders 2005 Criteria for Probable PDD (paraphrased) Exclusions No features suggesting another cause of mental impairment which when present makes it impossible to reliably diagnose PDD Emre et al. Movement Disorders 2005 Treatment of DLB and PDD Double-blind Placebo-Controlled Studies Rivastigmine McKeith et al. Lancet 2000 (DLB) Emre et al. NEJN 2004 (PDD)

14 Neuroleptic Sensitivity Avoid neuroleptics in DLB and PDD DLB 53% PDD 39% Aarsland et al J Clin Psychiatry, 2005 Conclusions DLB and PDD are common causes of dementia Cognitive and behavioural profile is different from AD DLB and PDD may represent different parts of a spectrum of Lewy body disease DLB and PDD may improve with cholinesterase inhibitors Avoid neuroleptics