Revised criteria for the clinical diagnosis of dementia with Lewy. Dementia with Lewy bodies. (Dementia with Lewy Bodies)
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1 Dementia with Lewy bodies First described: Okazaki H, 1961, Diffuse intracytoplasmic ganglionic inclusions (Lewy type) associated with progressive dementia and quadriparesis in flexion. J Neuropathol Exp Neurol; 20: Sima AAF et al, 1986 Lewy body dementia without Alzheimer changes, Can J Neurol Sci; 13(supp;):490-7 (Dementia with Lewy Bodies) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Mckeith et al 1996, Neurologu; 47: Revised criteria for the clinical diagnosis of dementia with Lewy bodies (DLB) McKeith IG et al, Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium. Neurology 2005; 65: Central Feature(essential for a diagnosis of possible or probable DLB) Dementia defined as progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational function. Prominent or persistent memory impairment may not necessarily occur in the early stages but is usually evident with progression. Deficits on tests of attention, executive function, and visualspatial ability may be especially prominent. Core features (two core features are sufficient for a diagnosis of probable DLB, one for possible DLB) Fluctuating cognition with pronounced variations in attention and alertness Recurrent visual hallucinations that are typically well formed and detailed Spontaneous features of parkinsonism Suggestive features (if one or more of these is present in the presence of one or more core features, a diagnosis of probable DLB can be made. In the absence of any core features, one or more suggestive features is sufficient for possible DLB. Probable DLB should not be diagnosed on the basis of suggestive features alone) REM sleep behavior disorder Severe neuroleptic sensitivity Low dopamine transporter uptake in basal Low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging
2 Supportive features (commonly present but not proven to have diagnostic specficity) 1. (fluctuating cognitive impairment) : Repeated falls and syncope Transient, unexplained loss of consciousness Severe autonomic dysfunction, e.g. orthostatic hypotension, urinary incontinence Halluciantions in other modalities Systematized delusions Depression Relative preservation of medial temporal lobe structures on CT/MRI scan Generalized low uptake on SPECT/PET perfusion scan with reduced occipital activity Abnormal (low uptake) MIBG nyocardial scintigaphy Prominent slow wave activity on EEG with temproal lobe transient sharp waved ( ) fluctuations A waxing and waning of cognition, functional ability, and arousal Variable attention, incoherent speech, hypersomnolence, impaired awareness of surrondings, staring into space, or appearing glazed or switched off Ferman TJ, Neurol Clin, 2007,25: fluctuation An early and prominent symptom Occurring in 80-90% during the course of disease Prevalence from 10-80% due to poor interrater reliability 50 to 75% McKeith I et al, Lancet Neurol 2004; 3:19-28 Walker MP et al, Demet Geriatr Cogn Disord 2000; 11: * The Mayo Fluctuations Composite Scale (1).Daytime drowsiness and lethargy (2).Daytime sleep of two or more hours (3).Staring into space for long periods (4).Episodes of disorganized speech 3 or 4 yes response indicate fluctuation (occur in 63% of DLB; 12% of AD) Ferman TJ, Neurology 2004; 62:181-7 * May be associated with REM sleep intrusion Clinical Assessment of Fluctuation, cut off value of >=5, in subsample of 40 cases, all 15 DLB had significant fluctuation, none of AD or controls in total 155 cases, 30/37 DLB--81%; 4/22 VD--18%; 5 /61AD 8% One Day Fluctuation Assessment Scale score>=6, 14/15DLB 93%,2/15AD 13%,0/10controls Walker MP et al, British Journal of psychiatry, 2000, 177, %&'()'* (psychiatric symptoms with persistent visual hallucinosis) : 80%
3 Visual hallucinations Recurrent, purely visual, vivid, colorful, 3- dimentional hallucinations of objects, humans or animals Some complain of seeing smoke or fire, or water on surface Detailed, formed VHs are often preceded by visual illusions or vivid dreams Occur early VHs are a marker of more severe cholinergic deficit in DLB Harding A.J., Brain, (2002), 125, Visual hallucinations in Lewy body disease relate to Lewy Bodies in the temporal lobe 25 pathologic diagnosis DLB cases NPI record visual hallucinations and other psychiatric features Oxford textbook of old age psychiatry, 2008 (parkinsonism) : 50-70% Parkinsonism Spontaneous More often Rigidity and bradykinesia than tremor Greater postural instability, gait difficulty, and facial impassivity, but less tremor than PDD More symmetric Posture/action tremor than rest Prominent orthstatic hypotension and constipation Less response to levodopa ) -. / ) ) ) Dopamine transporter imaging McKeith I, Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol, 2007 Apr; 6(4): (123)I-FP-CIT SPECT scan to assess probable (n=94) or possible (n=57) DLB or non-dlb dementia (n=147) --Abnormal scans had a mean sensitivity of 77.7% for detecting clinical probable DLB, with specificity of 90.4% for excluding non-dlb dementia, predominantly due to Alzheimer's disease. --A mean value of 85.7% overall diagnostic accuracy, 82.4% for positive predictive value, and 87.5% for negative predictive value. --The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from Alzheimer's disease.
4 In vivo Demonstration of Dopaminergic Deficit 4. Normal Alzheimer s Imaging with the dopaminergic presynaptic ligand [123I]-2carbomethoxy-3-(4-iodophenyl)- N-(3-fluoropropyl)nortropane (FP- CIT) and single-photon emission tomography. Can also use beta- O Normal CIT, IPT, TRODAT. AD DLB Right Putamen DLB Right Caudate Nucleus Left Caud ate N Left Putamen D Walker et al. Lancet 354: (1999) (20%) (65%) (40%) 1/3 (TIA) / -166"##* "##8755. Exclusion criteria In the presence of cerebrovascular disease, evident as focal neurological signs or on brain imaging In the presence of any other physical illness or brain disorder sufficient to account in part or in total for the clinical picture If parkinsonism only appears for the first time at a stage of severe dementia 9 : ; Parkinson s disease Motor Phase Lewy Bodies in substantia nigra and brainstem Diffuse Lewy Body Disease Neocortical and nigral LB Cell Loss Parkinson s Disease Nigral LB and cell loss PDD and DLB Lewy bodies in nigra, brainstem, limbic system and neorcortex. * Occasionally LBs can be in cortex without brainstem involvement I. McKeith Practical Neurology 7: (2007) PDD vs. DLB clinical manifestations : Similar in: Cognitive profile Attentional performance, Neuropsychiatric features, RBD, Autonomic dysfunction Type and severity of parkinsonism, Neuroleptic sensitivity Response to ChE-I Different in Temporal course (Parkinson s disease dementia PDD) (one-year rule) : DLB PDD
5 4) 6 87 DLB; 138AD; 103normal aging (NA) Impairment in basic attention, visual perception, visual construction and memory (compare DLB with NA) (sensitivity-88.6%; specificity-96.1%) Impaired visual construction and attention plus preserved memory and naming skill(compare DLB with AD)(sensitivity- 83.3%; specificity-91.4%) Ferman TJ et al, Neuropsychological differentiation of dementia with Lewy bodies from normal aging and Alzheimer s disease. Clin Neuropsychol 2006, 20: Central feature-progressive disabling mental impairment Substantial attentional deficits and prominent executive and visuospatial dysfunction Double discrimination: 1.Greater impairment of verbal fluency, visual perception and performance tasks than AD 2.Relative preservation of confrontation naming and short and medium term recall as well as recognition (McKeith IG 2005; Walker Z 1997; Connor DJ 1998; Mormont E 2003; Ferman TJ 2006) --9 pure DLB; 57 mixed DLB/AD; 66 pure AD --worse on tasks of verbal memory at AD pathology cases --worse on tasks of visual spatial skills at LB pathology cases --visual spatial performance but not verbal memory affected at combined pathology cases Johnson DK, et al, Verbal and visuospatial deficits in dementia with Lewy bodies. Neurology 2005; 65: AD, 65AD/LBP, 22LBP, total 135 autopsy cases Neuropsychologic test showed : 1.AD performed worse than the LBP patients on memory measures (Fuld Object Memory Evaluation Delayed Recall; Wechsler Memory Scale Logical Memory Immediate and Delayed Recall) and naming task (Consortium to Establish a Registry for Alzheimer s Disease Naming) 2.LBP cases were more impaired than AD on executive function (Trail Making Test Part B) and attention tasks (Wechsler Adult Intelligence Scale-Revised Digit Span) 3.Decline in MMSE and DRS (Dementia Rating Scale) scores over time were greatest in the AD/LBP cases Kraybill ML et al, Neurology 2005; 64: <= Table A comparison of clinical symptoms in Alzheimer's disease and dementia with Lewy bodies Dementia with Lewy bodies Alzheimer's disease At presentation (%) Ever (%) At presentation (%) Ever (%) Dementia 82 (40-100) Fluctuation 58 (8-85) 75 (45-90) 6 (3-11) 12 (5-19) Visual hallucinations 33 (11-64) 46 (13-80) 13 (3-19) 20 (11-28) Auditory hallucinations 19 (13-30) 19 (0-45) 1 (0-3) 4 (0-13) Depression 29 (7-75) 38 (12-89) 16 (9-38) 16 (12-21) Parkinsonism 43 (10-78) 77 (50-100) 12 (5-30) 23 (19-30) Falls 28 (10-38) 37 (22-50) 9 (5-14) 18 (11-24) Neuroleptic sensitivity 61 (0-100) 15 (0-29) Figures show mean (range). Based upon 261 cases of Alzheimer's disease and 190 cases of dementia with Lewy bodies, with autopsy confirmation of diagnosis. McKeith Ian 2002 The British Journal of Psychiatry 4 : > % +
6 /: )34 ) ) + 6 -,"###. &'A% I. McKeith Practical Neurology 7: (2007) : DLB : McKeith DLB rivastigmine 12mg 20 rivastigmine DLB 2 (63.4% Vs 30.0%) ChEIs FDA (parkinson s disease with dementia) AD ChEIs AD Rabins PV, Blacker D, Rovner BW, et al. American Psychiatric Association: Practice guideline for thetreatment of patients with Alzheimer s disease and other dementias. 2nd edition. Am J Psychiatry 2007;164(suppl 12):5-55.) =2/: BC) -8.=@2/ -> "##D. -".4-3"##(,"##D. -(. -@"##D. 62=2/ : EEF/: EE(#&# /) G 6/// BC:"#43362 (%*5 / 8&%D G 6/// BC4 -.-"##'/7F %. 36 +) 4=2/) BC =2/) -.4 % :66 /= % &'A)$ ( 234 '#H%5 BF Boeve et al Sleep Med. 4(4):281-4 (2003)
7 Think about tapering drugs first Anticholinergic, selegeline, dopamine agonist, levodopa Antihypertensive drugs Consider CEIs Cognition, psychosis, anxiety, apathy Psychosis: low dose quetiapine or clozapine Depression: CEIs, SSRI (avoid TCA) RBD can be treated with Clonazepam mg at bedtime Melatonin 3-12mg at bedtime Quetiapine 12.5mg at bedtime and titrated Parkinsonism: levodopa (may aggravate psychosis) Different from PD Orthostatic Hypotension: fludrocortisone, midodrine
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