- Parkinson’s disease
- Cognitive impairment
- Dementia with Lewy bodies
Parkinson’s disease (PD) is classically thought of as a movement disorder characterized by tremor, rigidity and postural instability. Nevertheless, there is growing recognition of prominent cognitive impairment in PD and related disorders, which is responsible for substantial disability in these patients. This review will focus on cognitive impairment associated with Lewy body pathology, including PD with dementia (PDD) and dementia with Lewy bodies (DLB). We will review the epidemiology, clinical evaluation, underlying mechanisms and treatment of cognitive impairment in these patients. Despite differences between PDD and DLB, there is clinical, neuropathological and radiological overlap between these disorders, supporting the view that they represent a spectrum of disease. These observations suggest that common targets for diagnosis and treatment of these disorders can be identified.
Copyright © 2008 S. Karger AG, Basel
- Parkinson J: An essay on the shaking palsy. 1817. J Neuropsychiatry Clin Neurosci 2002;14:223–236.
- Weintraub D, Moberg PJ, Duda JE, Katz IR, Stern MB: Effect of psychiatric and other nonmotor symptoms on disability in Parkinson’s disease. J Am Geriatr Soc 2004;52:784–788.
- Starkstein SE, Bolduc PL, Mayberg HS, Preziosi TJ, Robinson RG: Cognitive impairments and depression in Parkinson’s disease: a follow up study. J Neurol Neurosurg Psychiatry 1990;53:597–602.
- Aarsland D, Larsen JP, Tandberg E, Laake K: Predictors of nursing home placement in Parkinson’s disease: a population-based, prospective study. J Am Geriatr Soc 2000;48:938–942.
- Aarsland D, Larsen JP, Karlsen K, Lim NG, Tandberg E: Mental symptoms in Parkinson’s disease are important contributors to caregiver distress. Int J Geriatr Psychiatry 1999;14:866–874.
- Siderowf A, Ravina B, Glick HA: Preference-based quality-of-life in patients with Parkinson’s disease. Neurology 2002;59:103–108.
- Louis ED, Marder K, Cote L, Tang M, Mayeux R: Mortality from Parkinson disease. Arch Neurol 1997;54:260–264.
- Aarsland D, Ballard CG, Halliday G: Are Parkinson’s disease with dementia and dementia with Lewy bodies the same entity? J Geriatr Psychiatry Neurol 2004;17:137–145.
- Lippa CF, Duda JE, Grossman M, Hurtig HI, Aarsland D, Boeve BF, et al: DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers. Neurology 2007;68:812–819.
- McKeith IG: Spectrum of Parkinson’s disease, Parkinson’s dementia, and Lewy body dementia. Neurol Clin 2000;18:865–902.
- McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H, et al: Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005;65:1863–1872.
- Ravina B, Marder K, Fernandez HH, Friedman JH, McDonald WI, Murphy D, et al: Diagnostic criteria for psychosis in Parkinson’s disease: report of an NINDS, NIMH work group. Mov Disord 2007;19:1061–1068.
- Aarsland D, Litvan I, Salmon D, Galasko D, Wentzel-Larsen T, Larsen JP: Performance on the dementia rating scale in Parkinson’s disease with dementia and dementia with Lewy bodies: comparison with progressive supranuclear palsy and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2003;74:1215–1220.
- Ballard CG, Aarsland D, McKeith I, O’Brien J, Gray A, Cormack F, et al: Fluctuations in attention: PD dementia versus DLB with parkinsonism. Neurology 2002;59:1714–1720.
- Serrano C, Garcia-Borreguero D: Fluctuations in cognition and alertness in Parkinson’s disease and dementia. Neurology 2004;63:S31–S34.
- Horimoto Y, Matsumoto M, Nakazawa H, Yuasa H, Morishita M, Akatsu H, et al: Cognitive conditions of pathologically confirmed dementia with Lewy bodies and Parkinson’s disease with dementia. J Neurol Sci 2003;216:105–108.
- Barbas NR: Cognitive, affective, and psychiatric features of Parkinson’s disease. Clin Geriatr Med 2006;22:773–796.
- Cummings JL: The dementias of Parkinson’s disease: prevalence, characteristics, neurobiology, and comparison with dementia of the Alzheimer type. Eur Neurol 1988;28(suppl 1):15–23.
- Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sorensen P: Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol 2003;60:387–392.
- Chan SS, Chiu HF, Lam LC, Leung VP: Prevalence of dementia with Lewy bodies in an inpatient psychogeriatric population in Hong Kong Chinese. Int J Geriatr Psychiatry 2002;17:847–850.
- Perry RH, Irving D, Tomlinson BE: Lewy body prevalence in the aging brain: relationship to neuropsychiatric disorders, Alzheimer-type pathology and catecholaminergic nuclei. J Neurol Sci 1990;100:223–233.
- Shergill S, Mullan E, D’Ath P, Katona C: What is the clinical prevalence of Lewy body dementia? Int J Geriatr Psychiatry 1994;9:907–912.
- Heidebrink JL: Is dementia with Lewy bodies the second most common cause of dementia? J Geriatr Psychiatry Neurol 2002;15:182–187.
- Muslimovic D, Post B, Speelman JD, Schmand B: Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology 2005;65:1239–1245.
- Foltynie T, Brayne CE, Robbins TW, Barker RA: The cognitive ability of an incident cohort of Parkinson’s patients in the UK. The CamPaIGN study. Brain 2004;127:550–560.
- Hughes TA, Ross HF, Musa S, Bhattacherjee S, Nathan RN, Mindham RH, et al: A 10-year study of the incidence of and factors predicting dementia in Parkinson’s disease. Neurology 2000;54:1596–1602.
- Williams LN, Seignourel P, Crucian GP, Okun MS, Rodriguez RL, Skidmore FM, et al: Laterality, region, and type of motor dysfunction correlate with cognitive impairment in Parkinson’s disease. Mov Disord 2007;22:141–145.
- Hughes TA, Ross HF, Musa S, Bhattacherjee S, Nathan RN, Mindham RHS, et al: A 10-year study of the incidence of and factors predicting dementia in Parkinson’s disease. Neurology 2000;54:1596–1602.
- Levy G, Schupf N, Tang MX, Cote LJ, Louis ED, Mejia H, et al: Combined effect of age and severity on the risk of dementia in Parkinson’s disease. Ann Neurol 2002;51:722–729.
- Inzelberg R, Chapman J, Treves TA, Asherov A, Kipervasser S, Hilkewicz O, et al: Apolipoprotein E4 in Parkinson disease and dementia: new data and meta-analysis of published studies. Alzheimer Dis Assoc Disord 1998;12:45–48.
- Stern Y, Marder K, Tang MX, Mayeux R: Antecedent clinical features associated with dementia in Parkinson’s disease. Neurology 1993;43:1690–1692.
- Zgaljardic DJ, Foldi NS, Borod JC: Cognitive and behavioral dysfunction in Parkinson’s disease: neurochemical and clinicopathological contributions. J Neural Transm 2004;111:1287–1301.
- Hurtig HI, Trojanowski JQ, Galvin J, Ewbank D, Schmidt ML, Lee VM, et al: Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson’s disease. Neurology 2000;54:1916–1921.
- Vingerhoets G, Verleden S, Santens P, Miatton M, De Reuck J: Predictors of cognitive impairment in advanced Parkinson’s disease. J Neurol Neurosurg Psychiatry 2003;74:793–796.
- Mosimann UP, Mather G, Wesnes KA, O’Brien JT, Burn DJ, McKeith IG: Visual perception in Parkinson disease dementia and dementia with Lewy bodies. Neurology 2004;63:2091–2096.
- Lee C, Grossman M, Morris J, Stern MB, Hurtig HI: Attentional resource and processing speed limitations during sentence processing in Parkinson’s disease. Brain Lang 2003;85:347–356.
- Grossman M, Kalmanson J, Bernhardt N, Morris J, Stern MB, Hurtig HI: Cognitive resource limitations during sentence comprehension in Parkinson’s disease. Brain Lang 2000;73:1–16.
- Weintraub D, Moberg PJ, Culbertson WC, Duda JE, Katz IR, Stern MB: Dimensions of executive function in Parkinson’s disease. Dement Geriatr Cogn Disord 2005;20:140–144.
- Uekermann J, Daum I, Peters S, Wiebel B, Przuntek H, Muller T: Depressed mood and executive dysfunction in early Parkinson’s disease. Acta Neurol Scand 2003;107:341–348.
- Tiraboschi P, Salmon DP, Hansen LA, Hofstetter RC, Thal LJ, Corey-Bloom J: What best differentiates Lewy body from Alzheimer’s disease in early-stage dementia? Brain 2006;129:729–735.
- Polymeropoulos MH, Lavedan C, Leroy E, et al: Mutation in the α-synuclein gene identified in families with Parkinson’s disease. Science 1997;276:2045–2047.
- Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E: Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003;24:197–211.
- Colosimo C, Hughes AJ, Kilford L, Lees AJ: Lewy body cortical involvement may not always predict dementia in Parkinson’s disease. J Neurol Neurosurg Psychiatry 2003;74:852–856.
- Ballard C, Ziabreva I, Perry R, Larsen JP, O’Brien J, McKeith I, et al: Differences in neuropathologic characteristics across the Lewy body dementia spectrum. Neurology 2006;67:1931–1934.
- Apaydin H, Ahlskog JE, Parisi JE, Boeve BF, Dickson DW: Parkinson disease neuropathology: later-developing dementia and loss of the levodopa response. Arch Neurol 2002;59:102–112.
- Aarsland D, Perry R, Brown A, Larsen JP, Ballard C: Neuropathology of dementia in Parkinson’s disease: a prospective, community-based study. Ann Neurol 2005;58:773–776.
- Savitt JM, Dawson VL, Dawson TM: Diagnosis and treatment of Parkinson disease: molecules to medicine. J Clin Invest 2006;116:1744–1754.
- Pandey UB, Nie Z, Batlevi Y, McCray BA, Ritson GP, Nedelsky NB, et al: HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 2007;447:859–863.
- Lewis SJ, Dove A, Robbins TW, Barker RA, Owen AM: Cognitive impairments in early Parkinson’s disease are accompanied by reductions in activity in frontostriatal neural circuitry. J Neurosci 2003;23:6351–6356.
- Huang C, Mattis P, Tang C, Perrine K, Carbon M, Eidelberg D: Metabolic brain networks associated with cognitive function in Parkinson’s disease. Neuroimage 2007;34:714–723.
- Shaw LM, Korecka M, Clark CM, Lee VM, Trojanowski JQ: Biomarkers of neurodegeneration for diagnosis and monitoring therapeutics. Nat Rev Drug Discov 2007;6:295–303.
- Shimura H, Schlossmacher MG, Hattori N, Frosch MP, Trockenbacher A, Schneider R, et al: Ubiquitination of a new form of α-synuclein by parkin from human brain: implications for Parkinson’s disease. Science 2001;293:263–269.
- Scherzer CR, Eklund AC, Morse LJ, Liao Z, Locascio JJ, Fefer D, et al: Molecular markers of early Parkinson’s disease based on gene expression in blood. Proc Natl Acad Sci USA 2007;104:955–960.
- Brooks DJ: PET and SPECT studies in Parkinson’s disease. Baillieres Clin Neurol 1997;6:69–87.
- Jennings DL, Seibyl JP, Oakes D, Eberly S, Murphy J, Marek K: (123I) β-CIT and single-photon emission computed tomographic imaging versus clinical evaluation in Parkinsonian syndrome: unmasking an early diagnosis. Arch Neurol 2004;61:1224–1229.
- Walker Z, Costa DC, Walker RW, Lee L, Livingston G, Jaros E, et al: Striatal dopamine transporter in dementia with Lewy bodies and Parkinson disease: a comparison. Neurology 2004;62:1568–1572.
- Hilker R, Thomas AV, Klein JC, Weisenbach S, Kalbe E, Burghaus L, et al: Dementia in Parkinson disease: functional imaging of cholinergic and dopaminergic pathways. Neurology 2005;65:1716–1722.
- Rowe CC, Ng S, Ackermann U, Gong SJ, Pike K, Savage G, et al: Imaging β-amyloid burden in aging and dementia. Neurology 2007;68:1718–1725.
- Siderowf A, Newberg AB, Chou KL, Lloyd M, Colcher A, Hurtig H, et al: [99mTc]TRODAT-1 SPECT imaging correlates with odor identification in early Parkinson disease. Neurology 2005;64:1716–1720.
- Hawkes C: Olfaction in neurodegenerative disorder. Mov Disord 2003;18:364–372.
- Burn DJ, McKeith IG: Current treatment of dementia with Lewy bodies and dementia associated with Parkinson’s disease. Mov Disord 2003;18(suppl 6):S72–S79.
- Weintraub D, Siderowf AD, Potenza MN, Goveas J, Morales KH, Duda JE, et al: Association of dopamine agonist use with impulse control disorders in Parkinson disease. Arch Neurol 2006;63:969–973.
- Molloy SA, Rowan EN, O’Brien JT, McKeith IG, Wesnes K, Burn DJ: Effect of levodopa on cognitive function in Parkinson’s disease with and without dementia and dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2006;77:1323–1328.
- Contarino MF, Daniele A, Sibilia AH, Romito LM, Bentivoglio AR, Gainotti G, et al: Cognitive outcome 5 years after bilateral chronic stimulation of subthalamic nucleus in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 2007;78:248–252.
- Lippa CF, Smith TW, Perry E: Dementia with Lewy bodies: choline acetyltransferase parallels nucleus basalis pathology. J Neural Transm 1999;106:525–535.
- Perry EK, Curtis M, Dick DJ, Candy JM, Atack JR, Bloxham CA, et al: Cholinergic correlates of cognitive impairment in Parkinson’s disease: comparisons with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1985;48:413–421.
- Ravina B, Putt M, Siderowf A, Farrar JT, Gillespie M, Crawley A, et al: Donepezil for dementia in Parkinson’s disease: a randomised, double blind, placebo controlled, crossover study. J Neurol Neurosurg Psychiatry 2005;76:934–939.
- Miyasaki JM, Shannon K, Voon V, Ravina B, Kleiner-Fisman G, Anderson K, et al: Practice Parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006;66:996–1002.
- Aarsland D, Mosimann UP, McKeith IG: Role of cholinesterase inhibitors in Parkinson’s disease and dementia with Lewy bodies. J Geriatr Psychiatry Neurol 2004;17:164–171.
- McKeith I, del Ser T, Spano P, Emre M, Wesnes K, Anand R, et al: Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet 2000;356:2031–2036.
- Richard IH, Justus AW, Greig NH, Marshall F, Kurlan R: Worsening of motor function and mood in a patient with Parkinson’s disease after pharmacologic challenge with oral rivastigmine. Clin Neuropharmacol 2002;25:296–299.
- Parkinson Study Group: Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson’s disease. N Engl J Med 1999;340:757–763.
- Rabey JM, Prokhorov T, Miniovitz A, Dobronevsky E, Klein C: Effect of quetiapine in psychotic Parkinson’s disease patients: a double-blind labeled study of 3 months’ duration. Mov Disord 2007;22:313–318.
Andrew Siderowf, MD, MSCE
Department of Neurology, University of Pennsylvania School of Medicine
330 South 9th Street
Philadelphia, PA 19107 (USA)
Tel. +1 215 829 6500, Fax +1 215 829 6606, E-Mail firstname.lastname@example.org
Published online: December 5, 2007
Number of Print Pages : 11
Number of Figures : 0, Number of Tables : 4, Number of References : 73
Vol. 16, No. 1, Year 2008 (Cover Date: December 2007)
Journal Editor: Ip, N.Y. (Hong Kong)
ISSN: 1424–862X (print), 1424–8638 (Online)
For additional information: http://www.karger.com/NSG
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