- •What is the primary question addressed by this study?Do Parkinson's disease neuropsychiatric symptoms (depression, anxiety, and psychosis) correlate with neuronal loss/gliosis and Lewy body pathology in the substantia nigra and locus coeruleus?
- •What is the main finding of this study?Depression and psychosis, but not anxiety, were associated with neuronal loss/gliosis in the substantia nigra after controlling for disease duration and dementia. No neuropsychiatric symptoms were associated with Lewy body score.
- •What is the meaning of the finding?Neuronal loss/gliosis may be a better histopathological marker for neuropsychiatric symptoms in Parkinson's disease than Lewy body pathology.
The pathological hallmarks of Parkinson's disease include intraneuronal Lewy bodies, neuronal loss, and gliosis. We aim to correlate Parkinson's disease neuropsychiatric symptoms, (e.g., depression, psychosis, and anxiety) with the severity of neuropathology in the substantia nigra and locus coeruleus.
The brains of 175 participants with a primary pathologic diagnosis of Parkinson's disease were analyzed semi-quantitatively to ascertain the burden of neuronal loss and gliosis and Lewy body pathology within the locus coeruleus and substantia nigra. Participants’ history of anxiety, depression, and psychosis were determined using a chart-extracted medical history or record of formal psychiatric evaluation.
Of the sample, 56% (n = 98), 50% (n = 88), and 31.25% (n = 55) of subjects had a diagnosis of psychosis, depression, and anxiety, respectively. Psychosis (χ2 = 7.1, p = 0.008, df = 1) and depression (χ2 = 7.2, p = 0.007, df = 1) were associated with severe neuronal loss and gliosis in the substantia nigra but not in the locus coeruleus. No association was observed between anxiety and neuronal loss and gliosis in either region. No neuropsychiatric symptoms were associated with Lewy body score. After controlling for disease duration and dementia, psychosis (odds ratio [OR]: 3.1, 95% confidence interval [CI]: 1.5–6.4, χ2 = 9.4, p = 0.012, df = 1) and depression (OR: 2.6, 95% CI: 1.3–5.0, χ2 = 7.9, p = 0.005, df = 1) remained associated with severe neuronal loss and gliosis in the substantia nigra.
These results suggest that psychosis and depression in Parkinson's disease are associated with the underlying neurodegenerative process and demonstrate that cell loss and gliosis may be a better marker of neuropsychiatric symptoms than Lewy body pathology.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to The American Journal of Geriatric Psychiatry
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- The incidence of Parkinson's disease: a systematic review and meta-analysis.Neuroepidemiology. 2016; 46: 292-300
- EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson's disease.Eur J Neurol. 2013; 20: 16-34
- Non-motor features of Parkinson disease.Nat Rev Neurosci. 2017; 18: 435-450
- Neuropsychiatric symptoms in Parkinson's disease.Mov Disord. 2009; 24: 2175-2186
- The lewy body in Parkinson's disease and related neurodegenerative disorders.Mol Neurobiol. 2012; 47: 495-508
- The neuropathologic basis of different clinical subgroups of parkinson's disease.J Neuropathol Exp Neurol. 1991; 50: 743-755
- Post mortem studies in Parkinson's disease–is it possible to detect brain areas for specific symptoms?.J Neural Transm Suppl. 1999; : 1-29
- The neuropathological basis for depression in Parkinson's disease.Park Relat Disord. 2009; 15: 144-148
- Depression and Parkinson's disease: role of the locus coeruleus.Eur Psychiatry. 2015; 30: 641
- Depression in Parkinson's disease: Loss of dopamine and noradrenaline innervation in the limbic system.Brain. 2005; 128: 1314-1322
- Testing an aetiological model of visual hallucinations in Parkinson's disease.Brain. 2011; 134: 3299-3309
- Effect of psychiatric and other nonmotor symptoms on disability in Parkinson's disease.J Am Geriatr Soc. 2004; 52: 784-788
- Anxiety disorders in Parkinson's disease.Adv Neurol. 2005; 96: 42-55
- Idiopathic Parkinson's disease: Possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen.J Neural Transm. 2003; 110: 517-536
- Alpha-synuclein pathology does not predict extrapyramidal symptoms or dementia.Ann Neurol. 2005; 57: 82-91
- Lewy body pathology in normal elderly subjects.J Neuropathol Exp Neurol. 2009; 68: 816-822
- Disentangling the Relationship between Lewy bodies and nigral neuronal loss in Parkinson's disease.J Parkinsons Dis. 2011; 1: 277-286
- Motor score of the unified Parkinson disease rating scale as a good predictor of lewy body-associated neuronal loss in the substantia nigra.Arch Neurol. 2006; 63: 584-588
- A stable proportion of Lewy body bearing neurons in the substantia nigra suggests a model in which the Lewy body causes neuronal death.Neurobiol Aging. 2010; 63: 584-588
- Gait function and locus coeruleus Lewy body pathology in 51 Parkinson's disease patients.Park Relat Disord. 2016; 33: 102-106
- Diagnosis and management of dementia with Lewy bodies.Neurology. 2017; 89: 88-100
- Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium.Neurology. 2005; 65: 1863-1872
- A simple sequentially rejective multiple test procedure.Scand J Stat. 1979; 6: 65-70
- Visual hallucinations in Parkinson's disease: a review and phenomenological survey.J Neurol Neurosurg Psychiatry. 2001; 70: 727-733
- The psychosis spectrum in Parkinson disease.Nat Rev Neurol. 2017; 13: 81-95
- Structural and functional neuroimaging in patients with Parkinson's disease and visual hallucinations: a critical review.Park Relat Disord. 2015; 21: 683-691
- Clinical correlates of selective pathology in the amygdala of patients with Parkinson's disease.Brain. 2002; 125: 2431-2445
- Increased substantia nigra echogenicity correlated with visual hallucinations in Parkinson's disease: a Chinese population-based study.Neurol Sci. 2020; 41: 661-667
- Delusions and visual hallucinations in a patient with Parkinson's disease with dementia showing pronounced Lewy body pathology in the nucleus basalis of Meynert.Neuropathology. 2019; 13: 1-10
- Acute severe depression induced by intraoperative stimulation of the substantia nigra: a case report.Parkinsonism Relat Disord. 2008; 14: 253-256
- Etiological mechanisms of post-stroke depression: a review.Neurol Res. 2009; 31: 904-909
- The neurobiology and control of anxious states.Prog Neurobiol. 2003; 70: 83-244
- Depression and anxiety in Parkinson's disease: possible effect of genetic variation in the serotonin transporter.J Geriatr Psychiatry Neurol. 1999; 12: 49-52
- Inconsistencies and controversies surrounding the amyloid hypothesis of Alzheimer's disease.Acta Neuropathol Commun. 2014; 2: 135
- Contribution of somal Lewy bodies to neuronal death.Brain Res. 1997; 775: 24-29
Published online: December 21, 2020
Accepted: December 12, 2020
Received in revised form: November 30, 2020
Received: August 30, 2020
© 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.