1. MCI in Lewy Body Disorders: Definition, Frequency, Progression and Differentiation from Other MCI
Alexander I. Tröster, Ph.D.
Department of Neurology
University of North Carolina, Chapel Hill

2. Overview Nomenclature of Lewy body disorders
Factors leading to consideration of “MCI” as an entity in Parkinson’s disease (PD)
Potential benefits of identifying MCI in PD
Frequency and subtypes of MCI in PD
Conversion of MCI to PDD and DLB
Dementia and the neuropsychological characteristics of the PDD prodrome
Comparisons of neuropsychological characteristics of early PDD/DLB and Alzheimer’s disease
Challenges facing the concept of MCI in Lewy body disorders
Tröster 2009

3. Nomenclature of Lewy Body Disorders DLB/PDD Work Group (Lippa et al
Parkinson’s disease (PD)
Parkinson’s disease with dementia (PDD)
Dementia with Lewy bodies (DLB)
Lewy body dementias
Distinction in temporal sequence of onset of motor symptoms and dementia in PDD and DLB retained in recent criteria (12 Month Rule)
Tröster 2009

4. Cognitive Impairment in PD
Cognitive changes in PD without dementia recognized for decades
Cognitive changes near time of diagnosis recognized only recently (Foltynie et al. 2004, Muslimovic et al., 2005)
First to refer to MCI in PD was review by Fernandez et al. 2005
Tröster 2009

5. Possible Factors Prompting Consideration of MCI in PD
Acknowledgement of MCI heterogeneity and subtypes (Petersen 2004)
Recognition of a) heterogeneous, and b) very early cognitive decrements in PD (Muslimovic et al. 2005)
Neuropathologic staging of PD compatible with pre-diagnostic non-motor symptoms (Braak et al.2003)
Tröster 2009

6. Possible Advantages of MCI Diagnosis in PD
Early detection and treatment of cognitive decline, and consequent enhancement of functioning
Evaluation of DLB/PDD distinction
Greater precision in identifying course of cognitive decline, risk factors for these declines, and underlying mechanisms
Tröster 2009

7. Evaluation and MCI Subtypes
Tröster 2009

8. Montreal Cognitive Assessment (MOCA) Nasreddine et al. 2005
Tröster 2009

9. MCI Subtypes and Frequency in Parkinson’s Disease

10. Cognitive Impairment in Newly Diagnosed PD Muslimovic et al. 2005
24% (27) 3+ tests impaired; 38% 2+ tests impaired
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14. Progression of MCI to Parkinson’s Disease with Dementia (PDD)

15. Tröster 2009

16. MCI Progression to Dementia in PD
Foltynie et al. (2004) did not define MCI but found 36% of newly diagnosed PD had cognitive impairment per one or more of MMSE and CANTAB Tower and Pattern Recognition
Follow-up 3-5 years later (Williams-Gray et al. 2007) found the cognitive groupings were not informative of subsequent dementia, but dementia was associated with deficits on cognitive tests of “posterior” cortical functions (semantic fluency, pattern recognition, pentagon copying).
Tröster 2009

17. Dementia and the Neuropsychological Characteristics of the PDD Prodrome

18. A Transition in Grouping PD Patients by Cognitive Impairment
Tröster 2009

19. Neuropsychological Predictors of PDD Studies with Limited Assessment Instruments
Piccirilli et al. (1989):
6/8 with (but only 1/22 without) “frontal dysfunction” per Luria tasks at baseline developed dementia at 4-year follow-up
Biggins et al. (1992):
Baseline WAIS Verbal & MMSE (but not WMS or WAIS Picture Completion) lower in 10 patients (of 82) developing dementia (54 months) than in 41 patients not developing dementia over 36 months
Tröster 2009

20. Jacobs et al. (1995): Mahieux et al. (1998):
Neuropsychological Predictors of PDD Studies with Multiple Assessment Instruments
Jacobs et al. (1995):
23 of 111 (122) developed dementia
at least 1 year follow-up
predictors: lexical and semantic verbal fluency (without covariates, also immediate recall)
Mahieux et al. (1998):
19 of 81 (89) developed dementia
3.5 year follow-up
predictors: WAIS-R Picture Completion, Stroop interference, and lexical verbal fluency
Tröster 2009

21. Neuropsychological Predictors of PDD Studies with Multiple Assessment Instruments
Woods & Tröster (2003)
20 developed dementia after 1 year, 18 studied and compared to 18 PD not developing dementia
PDD had poorer baseline performance in:
Memory (CVLT Immediate recall & recognition)
Executive function (WCST Perseverative Errors)
Working memory (Digits backwards)
Each of the 4 scores had good sensitivity in predicting PDD, but ≥ 2 of 4 scores impaired per ROC curve had 0.75 overall predictive power
Tröster 2009

22. Progression of MCI to Dementia with Lewy Bodies (DLB)

23. Progression from MCI to DLB
No MCI studies with DLB focus; two MCI studies incidentally/secondarily mention DLB
Jicha et al. (2006)
34 amnestic-MCI developing dementia came to autopsy
1 had final clinical diagnosis of DLB
3 had neuropathologic diagnosis of Lewy body disease
Fischer et al. (2007)
141 MCI and 440 normal followed 30 mos.
Possible DLB in 10 patients with AD
Baseline: 4 normal, 4 non-amnestic MCI, 2 amnestic MCI
Tröster 2009

24. Neuropsychological Differentiation of LBD MCI and Other MCI

25. Retrospective Comparison of MCI-AD and MCI-DLB Jicha et al. 2009
Neuropathological database search
15 neuropathologically confirmed DLB (without significant comorbidity); 9 with predementia cognitive decline data
12 of 16 neuropathologically confirmed AD with predementia cognitive decline data
MCI required memory complaint and impairment with intact functioning
MCI-DLB: worse phonemic fluency
MCI-AD: worse immediate paragraph recall
Trends
MCI-DLB slower on Trailmaking Part A
MCI-AD worse on BNT, delayed wordlist recall
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26. Neuropsychological Comparisons of DLB, PDD and AD & Inferences about MCI Characteristics
Caution needed in assuming neuropsychological differences in early dementia parallel those in MCI
Assumes rate of progression of different deficits is similar
Assumes linear progression of deficits
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27. Neuropsychological Comparison of DLB/PDD vs. AD
AD involves greater impairment of memory, especially verbal (e.g., Noe et al., 2004; Simard et al. 2002), probably related to greater temporal lobe pathology
AD hallmarks: rapid rates of forgetting and intrusions
DLB involves greater visuoperceptual and constructional deficits (e.g., Simard et al. 2003; Calderon et al. 2001), which may be linked to posterior cortical hypometabolism and vissal hallucinations
Tröster 2009

28. Neuropsychological Comparison of DLB/PDD vs. AD
DLB/PDD perform worse than AD on complex attention tasks (Stroop, Trailmaking) (Calderon et al. 2001) but not on simple tasks (e.g., digit span) (Salmon et al. 1996)
DLB/PDD perform worse on executive function tasks (e.g., card sorting) than AD (Simard et al. 2000; Paolo et al. 1995). Executive dysfunction linked to basal forebrain cholinergic deficits
Language data more equivocal: same naming and fluency deficits in AD and DLB, worse naming in AD, worse letter fluency in DLB
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29. Summary of MCI in LBD

30. Summary of MCI in LBD
MCI is present in 19% to 53% of PD, with most reports in the 20%-30% range
In PD, MCI single domain more common than multiple domain
Executive/attention seems most common domain of MCI in PD
Executive/attention, and to lesser extent, immediate recall impairments are associated with development of dementia
Virtually nothing known about MCI in DLB
LBD MCI is neuropsychological differentiable from MCI/early AD
Tröster 2009

31. Challenges to MCI in LBD

32. Challenges to the Concept of MCI in LBD
Problems of studying MCI especially in DLB – low yield of DLB in MCI up to now. Will subtyping help? Should we start with MCI with parkinsonism?
Many clinicians and patients think of MCI as a disease (or early AD) vs. a syndrome, thus risking confusion and fear of AD in PD
Should behavioral abnormalities be considered in MCI given the PDD criteria?
Tröster 2009

33. Challenges to the Concept of MCI in LBD
Definition of MCI: which tests, which scores?
How will MCI diagnosis aid treatment in PD?
Role of PD medications in producing and alleviating/masking MCI?
Should we call it PDCI analogous to vascular CI?
Is memory impairment primary or secondary – affects definition of single vs. multiple domain MCI?
Are subtypes too gross for prognostic purposes?
Tröster 2009