In previous studies among patients with Parkinson disease (PD) who were administered the Apathy Evaluation Scale (AES), between 12% and 51% evidenced clinically significant apathy. Although apathy is a risk factor for dementia, its causes and clinical correlates have not been adequately studied. In particular, side of onset of disease, though a likely predictor of apathy and dementia, has not been thoroughly investigated.
Methods:
A total of 30 mid-stage patients with PD and 35 community-dwelling elderly control patients (CPs) were administered the AES (self version) along with a battery of cognitive and neuropsychiatric assessments. Persons close to patients with PD and CPs completed the AES—other (informant) version about the patient or CP. Multiple linear regression analysis examined predictors of apathy severity after controlling for mood, levodopa dosage equivalents (LDEs), gender, age, and disease severity (Hoehn–Yahr [H-Y] stage).
Results:
Patients with right-onset disease more frequently exhibited apathy and evidenced significantly higher total AES scores than left-onset patients with PD or CPs (P < .03). Of all the patients, 42% with right-onset PD versus 11.1% of the patients with left-onset PD exhibited clinically significant levels of apathy. There were no differences for self versus informant scores for right-onset patients with PD. The AES scores were not correlated with depression, stress, anxiety, LDEs, gender, age, and H-Y stage. There were no gender differences for any AES variables.
Conclusion:
Clinically significant levels of apathy are much more likely to occur in patients with right-onset disease. These patients may be at greater risk of PD-related dementia.
LevyR. Apathy: a pathology of goal-directed behavior: a new concept of the clinic and pathophysiology of apathy. Rev Neurol (Paris). 2012;168(8-9):585–597.
3.
LevyRDuboisB. Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb Cortex. 2006;16(7):916–928.
4.
BenoitMRobertPH. Imaging correlates of apathy and depression in Parkinson’s disease. J Neurol Sci. 2011;310(1-2):58–60.
5.
LevyMLCummingsJLFairbanksLAApathy is not depression. J Neuropsychiatry Clin Neurosci. 1998;10(3):314–319.
6.
DursoR. Dementia in Parkinson disease. In: McNamaraP, ed. Dementia: Volume 2: Science and Biology. Santa Barbara, CA: Praeger Publishers; 2011:159–182.
7.
HarrisE. Relation of apathy to dementia in patients with Parkinson’s disease. In: McNamaraP, ed. Dementia: Volume 2: Science and Biology. Santa Barbara, CA: Praeger Publishers; 2011:221–236.
8.
StarksteinSEMaybergHSLeiguardaR, et al. A prospective longitudinal study of depression, cognitive decline, and physical impairments in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 1992;55(5):377–382.
9.
Kirsch-DarrowLFernandezHFMarsiskeM, et al. Dissociating apathy and depression in Parkinson disease. Neurol. 2006;67(1):33–38.
10.
CuboEBenito-LeonJCoronellCArmestoD. Clinical correlates of apathy in patients recently diagnosed with Parkinson’s disease: the ANIMO study. Neuroepidemiology. 2012;38(1):48–55.
11.
KosticVSFilippiM. Neuroanatomical correlates of depression and apathy in Parkinson’s disease: magnetic resonance imaging studies. J Neurol Sci. 2011;310(1-2):61–63.
12.
ReijndersJSScholtissenBWeberWE, et al. Neuroanatomical correlates of apathy in Parkinson’s disease: a magnetic resonance imaging study using voxel-based morphometry. Mov Disord. 2010;25(14):2318–2325.
13.
HughesAJDanielSEKilfordLLeesAJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinic-pathological study of 100 cases. J Neurol Neurosurg Psychiatr. 1992;55(3):181–184.
14.
American Psychiatric Association (APA). Diagnostic and Statistical Manual for Mental Disorders, Text Revision. 4th ed.Washington, DC: American Psychiatric Association; 2000.
15.
Jimenez-ShahedJBakerKDavidsonAJankovicJ. The role of dopaminergic medication doses in impulse control disorders in Parkinson’s disease. Mov Disord. 2008;23(suppl 1):S82.
16.
UittiRJBabaYWhaleyNR, et al. Parkinson’s disease: handedness predicts asymmetry. Neurol. 2005;64(11):1925–1930.
17.
GoetzCGTilleyBCShaftmanSRMovement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008;23(15):2129–2170.
18.
FolsteinMFolsteinSMcHughP. “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–198.
19.
PagonabarragaJKulisevskyJLlebariaGParkinson’s disease-cognitive rating scale: a new cognitive scale specific for Parkinson’s disease. Mov Disord. 2008;23(7):998–1005.
20.
LovibondSHLovibondPF. Manual for the Depression Anxiety Stress Scales. Sydney: The Psychology Foundation of Australia, Inc.; 1995.
21.
McNamaraPDursoRHarrisE. “Machiavellianism” and frontal dysfunction: evidence from Parkinson’s disease (PD). Cogn Neuropsychiatry. 2007;12(4):285–300.
22.
McNamaraPStavitskyKDursoRHarrisE.The impact of clinical and cognitive variables on social functioning in Parkinson's disease: patient versus examiner estimates. Parkinsons Dis2010. pii 263083:6 pages.
23.
McNamaraPStavitskyKHarrisE, et al. Mood, side of motor symptom onset and pain complaints in Parkinson’s disease. Int J Geriatr Psychiatry. 2010;25(5):519–524.
24.
AntonyMMBielingPJCoxBJ, et al. Psychometric properties of the 42-item and 21-item versions of the Depression Anxiety Stress Scales (DASS) in clinical groups and a community sample. Psychol Assess. 1998;10(2):176–181.
25.
CrawfordJRHenryJD. The Depression Anxiety Stress Scales (DASS): normative data and latent structure in a large non-clinical sample. Br J Clin Psychol. 2003;42(pt 2):111–131.
26.
GoldenCJFreshwaterSM. The Stroop Color and Word Test: A Manual for Clinical and Experimental Uses. Chicago, IL: Stoelting Co.; 2002.
27.
ButterfieldLCCiminoCROelkeLE, et al. The independent influence of apathy and depression on cognitive functioning in Parkinson’s disease. Neuropsychology. 2010;24(6):721–730.
28.
PluckGCBrownRG. Apathy in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2002;73(6):636–642.
29.
RabkinJGFerrandoSJvan GorpW, et al. Relationships among apathy, depression, and cognitive impairment in HIV/AIDS. J Neuropsychiatry Clin Neurosci. 2000;12(4):451–457.
30.
BrückAPortinRLindellAPositron emission tomography shows that impaired frontal lobe functioning in Parkinson’s disease is related to dopaminergic hypofunction in the caudate nucleus. Neurosci Lett. 2001;311(2):81–84.
31.
Kirsch-DarrowLZahodneLBMarsiskeM, et al. The trajectory of apathy after deep brain stimulation: from pre-surgery to 6 months post-surgery in Parkinson’s disease. Parkinsonism Rel Disord. 2011;17(3):182–188.
32.
OguruMTachibanaHTodaK, et al. Apathy and depression in Parkinson disease. J Geriatr Psychiatry Neurol. 2010;23(1):35–41.
33.
StarksteinSEMerelloMJorgeR, et al. The syndromal validity and nosological position of apathy in Parkinson’s disease. Mov Disord. 2009;24(8):1211–1216.
34.
DrijgersRLDujardinKReijndersJS, et al. Validation of diagnostic criteria for apathy in Parkinson’s disease. Parkinsonism Rel Disord. 2010;16(10):656–660.
35.
CummingsJL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurol. 1997;48(suppl 6):S10–S16.
36.
PedersenKFAlvesGAarslandDLarsenJP. Occurrence and risk factors for apathy in Parkinson disease: a 4-year prospective longitudinal study. J Neurol Neurosurg Psychiatry. 2009;80(11):1279–1282.
37.
PedersenKFAlvesGBrønnickK, et al. Apathy in drug-naïve patients with incident Parkinson’s disease: the Norwegian ParkWest study. J Neurol. 2010;257(2):217–223.
38.
DujardinKSockeelPDevosDCharacteristics of apathy in Parkinson’s disease. Mov Disord. 2007;22(6):778–784.
39.
DujardinKSockeelPDelliauxM, et al. Apathy may herald cognitive decline and dementia in Parkinson’s Disease. Mov Disord. 2009;24(16):2391–2397.
40.
SockeelPDujardinKDevosD, et al. The Lille Apathy Rating Scale (LARS), a new instrument for detecting and quantifying apathy: validation in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2006;77(5):579–584.
41.
RobertPHClairetSBenoitMThe apathy inventory: assessment of apathy and awareness in Alzheimer’s disease, Parkinson’s disease and mild cognitive impairment. Int J Geriatr Psychiatry.2002;17(12):1099–1105.
42.
Martinez-CorralMPagonabarragaJLlebariaGFacial emotion recognition impairment in patients with Parkinson’s Disease and isolated apathy. [published online ahead of print July 28, 2010]Parkinsons Dis. Article ID 930627.
43.
LevyRCzerneckiV. Apathy and the basal ganglia. J Neurol. 2006;253(suppl 7):54–61.
44.
CramerCKFriedmanJHAmickMM. Olfaction and apathy in Parkinson’s disease. Parkinsonism Rel Disord. 2010;16(2):124–126.
45.
AgidYCerveraPHirschEBiochemistry of Parkinson’s disease 28 years later: a critical review. Mov Disord. 1989;4(suppl 1):S126–S144.
46.
IsellaVMelziPGrimaldiMClinical, neuropsychological, and morphometric correlates of apathy in Parkinson’s disease. Mov Disord. 2002;17(2):366–371.
DelgadoM. Reward-related responses in the human striatum. Ann N Y Acad Sci. 2007;1104:70–88.
49.
HaaxmaCAHelmichRCBormGF, et al. Side of symptom onset affects motor dysfunction in Parkinson’s disease. Neuroscience. 2010;170(4):1282–1285.
50.
KempsterPAGibbWRGSternGMLeesAJ. Asymmetry of substantia nigra neuronal loss in Parkinson’s disease and its relevance to the mechanism of levodopa related motor fluctuations. J Neurol Neurosurg Psychiatry. 1989;52(1):72–76.
51.
DethySvan BlercomNDamhautP, et al. Asymmetry of basal ganglia glucose metabolism and dopa responsiveness in parkinsonism. Mov Disord. 1998;13(2):275–280.
52.
DjaldettiRZivIMelamedE. The mystery of motor asymmetry in Parkinson’s disease. Lancet Neurol. 2006;5(9):796–802.
53.
DjaldettiRTrevesTAZivI, et al. Use of a single [123I]-FP-CIT SPECT to predict the severity of clinical symptoms of Parkinson disease. Neurol Sci. 2009;30(4):301–305.
54.
DjaldettiRLorberboymMKarmonY, et al. Residual striatal dopaminergic nerve terminals in very long-standing Parkinson’s disease: a single photon emission computed tomography imaging study. Mov Disord. 2011;26(2):327–330.
55.
MorrishPKSawleGVBrooksDJ. Clinical and [18F]dopa PET findings in early Parkinson’s disease. J Neurol Neurosurg Psychiatry1995; 59:597–600.
56.
HarrisE. Neurocognition and self-regulation of the agentic self in patients with Parkinson’s disease(Doctoral dissertation). Boston University, Boston, MA, 2011.
57.
BlakemoreS-JFrithC. Self-awareness and action. Curr Opin Neurobiol. 2003;13(2):219–224.
58.
FrithCDBlakemoreS-JWolpertDM. Abnormalities in the awareness and control of action. Philos Trans R Soc Lon B Biol Sci. 2000;355(1404):1771–1788.
59.
GallagherS. Philosophical conceptions of the self: implications for cognitive science. Trends Cogn Sci. 2000;4(1):14–21.
60.
HaggardP. Human volition: towards a neuroscience of will. Nat Rev Neurosci. 2008;9(12):934–946.
HaggardPClarkSKalogerasJ. Voluntary action and conscious awareness. Nat Neurosci. 2002;5(4):382–385.
63.
McNamaraP. The Cognitive Neuropsychiatry of Parkinson’s Disease. Cambridge, MA: The MIT Press; 2011.
64.
MooreJHaggardP. Awareness of action: inference and prediction. Conscious Cogn. 2008;17(1):136–144.
65.
MooreJWWegnerDMHaggardP. Modulating the sense of agency with external cues. Conscious Cogn. 2009;18(4):1056–1064.
66.
MooreJWSchneiderSASchwingenschuhP, et al. Dopaminergic medication boosts action-effect binding in Parkinson’s disease. Neuropsychologia. 2010;48(4):1125–1132.
67.
SynofzikMVosgerauGNewenA. Beyond the comparator model: a multifactorial two-step account of agency. Conscious Cogn. 2008;17(1):219–239.
68.
CooperRPSchwartzMFYulePShalliceT. The simulation of action disorganization in complex activities of daily living. Cogn Neuropsychol. 2005;22(8):959–1004.
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