Impulse Control Disorders, Psychosis, and Cognitive Impairment in Parkinson Disease

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CATEGORY 1 CME

Premiere Date: June 20, 2025

Expiration Date: December 20, 2026

This activity offers CE credits for:

1. Physicians (CME)

2. Other

All other clinicians either will receive a CME Attendance Certificate or may choose any of the types of CE credit being offered.

ACTIVITY GOAL

To understand the epidemiology of Parkinson disease symptoms.

LEARNING OBJECTIVES

1. Discuss the epidemiology of neuropsychiatric symptoms of Parkinson disease.

2. Describe the assessment of neuropsychiatric symptoms of Parkinson disease.

3. Enumerate the evidence-based treatments for neuropsychiatric symptoms of Parkinson disease.

TARGET AUDIENCE

This accredited continuing education (CE) activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve their care for patients with mental health disorders.

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This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Physicians’ Education Resource,® LLC and Psychiatric Times®. Physicians’ Education Resource, LLC, is accredited by the ACCME to provide continuing medical education for physicians.

Physicians’ Education Resource, LLC, designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits.™ Physicians should claim only the credit commensurate with the extent of their participation in the activity.

This activity is funded entirely by Physicians’ Education Resource, LLC. No commercial support was received.

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Editor’s Note: Please see the April CME article for more information on depression, apathy, and anxiety in Parkinson disease.

Neuropsychiatric symptoms (NPS) are common among individuals with Parkinson disease (PD), with cross-sectional studies indicating prevalence rates of 70% to 89%.¹ Although common, these symptoms are often underrecognized and not adequately treated, adding to the disability caused by the illness.² NPS that are seen among individuals with PD include depression, apathy, anxiety, impulse control disorders (ICDs), psychosis, and cognitive impairment including dementia. Depression, apathy, and anxiety were covered in Part 1 of this CME activity.

Psychosis

A meta-analysis by Chendo et al found that among individuals with PD, the pooled frequency of psychosis (hallucinations, delusions, and minor psychotic phenomena, including sense of presence, passage hallucinations, and illusions) was 20.7%.³ In another study, the investigators noted that visual hallucinations were present in approximately a quarter to a third of individuals with PD and auditory hallucinations were seen in about 20% of the individuals. Minor phenomena were seen in approximately 17% to 72% of the individuals and delusions were noted among 5% of the people with PD.⁴ According to data, further factors associated with the development of PD psychosis (PDP) can be found in the Table.⁴

TABLE. Factors Associated With Development of Parkinson Disease Psychosis⁴

Results of 1 study showed that among individuals with PD and hallucinations at baseline (33%), the occurrence of the hallucinations increased to 44% at 18 months and 63% at 48 months (P <.0001).⁵ The investigators found that time was the only significant factor influencing the development of hallucinations over the 48-month period. In many of these cases, hallucinations may become worse. One study found that hallucinations worsened in 95% of cases during a 3-year follow-up period. A recent meta-analysis also found a significant positive association between psychosis and cognitive impairment (standardized mean difference [SMD], 0.44), and psychosis and disease progression (SMD, 0.46).⁶

Results of another meta-analysis showed that individuals with PDP have worse functioning on all major cognitive domains when compared with individuals with PD, but without psychosis including global cognition (Hedges g = —0.57), processing speed (Hedges g = —0.58), executive functions (Hedges g = —0.56), episodic memory (Hedges g = —0.58), and perception (Hedges g= —0.55) as the most likely affected domains.⁷ Another meta-analysis found that individuals with PDP had lower grey matter volume (GMV) in parietal-temporo-occipital regions and the GMV loss in PDP was associated with local gene expression of 5-HT1a (P = .012) and 5-HT2a receptors (P = .002) but not dopaminergic receptors.⁸

The consensus guidelines developed by the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health working group for the diagnosis of PDP indicate that for making a diagnosis of PDP, a confirmed diagnosis of PD with the onset of 1 or more PDP-associated symptoms including hallucinations, illusions, delusions, or false sense of presence with a duration of at least 1 month should be present.⁹ It is also important to rule out secondary causes of psychosis including medical, psychiatric, medication effects, and substance use disorders. A diagnosis of PDP can be made if the psychotic symptoms continue despite removal of other potential reasons for psychosis.¹⁰ Part 1 of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (UPDRS) and the enhanced Scale for the Assessment of Positive Symptoms in PD that are completed with the patients and their caregivers can assist in the diagnosis of PDP.

One meta-analysis found that cholinesterase inhibitors (CHIs) improved delusions (SMD, −0.14; P = .04) and hallucinations (SMD, —0.08; P = .01) among individuals with PD.¹¹ Although there were no significant differences noted among the various CHIs, rivastigmine showed the largest effect size for both delusions (SMD, —0.11; P = .03) and hallucinations (SMD, —0.10; P = .01). The investigators also found a significant effect size for CHIs on the total neuropsychiatric score (SMD, —0.18; P = .002). They also noted a significant interaction between the treatment effect and the baseline neuropsychiatric total score (P = .02) when compared with placebo, indicating that an increase in baseline neuropsychiatric score increased the effect size in favor of medication treatment. A significant interaction between treatment outcome of total neuropsychiatric score and baseline Mini Mental State Examination (MMSE) score was noted (P = .008), indicating that a decrease in baseline MMSE score increased the effect size in favor of medication treatment when compared with placebo.

In another network meta-analysis, Yunusa et al found that on the Clinical Global Impression Scale for Severity, pimavanserin (SMD, —4.81), clozapine (SMD, —4.25), and quetiapine (SMD, —1.15) significantly improved severity of psychotic symptoms when compared with placebo.¹² On the Scale for Assessment of Positive Symptoms for Parkinson Disease, pimavanserin (OR, 1.16) improved psychotic symptoms when compared with placebo. On the UPDRS, clozapine (SMD, −0.69), pimavanserin (SMD, —0.01), and quetiapine (SMD, 0.00) did not impair motor functioning. Quetiapine (SMD, 0.60) impaired cognition (MMSE scores) when compared with placebo. Results of this study found that pimavanserin and clozapine were most efficacious and safe with pimavanserin having the greatest probability of being efficacious when used among individuals with PDP. Pimavanserin is FDA approved for the treatment of PDP.

In a second network meta-analysis, Srisurapanont et al found that clozapine (SMD, —1.31) and pimavanserin (SMD, —0.30) were superior to the placebo in treating psychotic symptoms among individuals with PD, whereas quetiapine (SMD, 0.47) was found to be inferior to placebo.¹³ Clozapine was ranked first in reducing psychotic symptoms (P-score = 1.00), followed by pimavanserin (P-score = 0.73). Clozapine was ranked first (P-score = 0.81) in preventing the worsening of abnormal movements. The authors concluded that clozapine emerged as the medication with the highest efficacy (large treatment effect) and exhibited minimal motor adverse effects, had high acceptability and moderate overall tolerability. Pimavanserin was ranked second in terms of efficacy (small-to-moderate treatment effect) and was associated with moderate motor adverse effects, overall tolerability, and acceptability.

One meta-analysis that evaluated data from 5 studies found that electroconvulsive therapy (ECT) was effective in treating psychotic symptoms among individuals with PD (SMD, 1.64, P <.001).¹⁴ Results of this study also showed that cognition improved after ECT among these individuals (SMD, 0.21; P = .002).

Available evidence from these studies indicates that pimavanserin and clozapine are first-line medications to treat psychotic symptoms among individuals with PD. Quetiapine can be considered as a second-line medication to treat symptoms of PDP. CHIs, especially rivastigmine, may also be useful in treatment of PDP. ECT can be used for the treatment of psychotic symptoms that are not amenable to treatment with pimavanserin, clozapine, and/or quetiapine.

ICDs

ICDs are characterized by an inability to resist an inappropriate drive, resulting in repetitive behaviors that can lead to harmful consequences to the individual.¹⁵ The most common ICDs include pathological gambling, compulsive sexual behavior, compulsive eating, and compulsive shopping. ICDs are seen in approximately 18.5% of individuals with PD.¹⁶ Impulsive-compulsive behaviors (ICBs) refer to repetitive, excessive, and compulsive behaviors that are driven by some strong desire and are often difficult to control. ICBs are seen in approximately 14.64% of individuals with PD.¹⁷

Available evidence indicates that the ICD worsens quality of life, activities of daily living, and emotional well-being (P <.004) among individuals with PD.¹⁸ One meta-analysis found that when compared with individuals who have PD and no ICD, individuals with PD and ICD had worse abstraction ability/concept formation (Hedges g = —0.40), set shifting (Hedges g = —0.59 and —0.46), visuospatial/constructional ability (Hedges g = —0.42), and decision-making (Hedges g = 0.54).¹⁹

One meta-analysis that included data from 15 studies found that risk factors for individuals with PD developing ICD were younger age (SMD, —0.39, P <.01), male sex (OR, 1.64; P <.01), smoking habit (OR, 2.28; P = .02), dopamine receptor agonist (DA) use (OR, 3.41; P <.01), DA equivalent daily dose (SMD, 0.42; P = .003), levodopa equivalent daily dose (total LEDD; SMD, 0.32; P <.01), and amantadine use (OR, 2.26; P <.01).²⁰

ICBs have been noted to be more common among Caucasians (17.9%) than among Asians (12.4%) with PD.¹⁷ Risk factors for ICBs among individuals with PD are younger age (P <.0001), male sex (OR, 1.64; P = .001), longer course of PD (P = .005), higher depression scores (Hamilton Depression Rating Scale, P = .007), more levodopa dosage (P = .02), DA use (P <.00001), higher average dose (levodopa, P = .0003; DA, P <.00001), as well as more amantadine use (P = .0004). One meta-analysis also found that rapid eye movement behavior disorder was associated with a more than 2-fold greater risk of developing ICBs (OR, 2.12; P <.01).²¹

A meta-analysis found that there were no significant changes in any cortical or subcortical regions among individuals with PD and ICD.²² However, there was increased activity noted in the ventral striatum and orbitofrontal cortex and decreased activity in anterior cingulate cortex (ACC) among these individuals. Additionally, clusters of hyperactivation in ventral striatum and of hypoactivation in ACC were also noted in the meta-analysis. These findings indicate strongly that ICD in PD is related to a dysfunction of limbic divisions of the striatum and of the prefrontal cortex. One meta-analysis found that there was no significant impairment identified in reward processing in patients with PD and ICD when compared with patients with PD and without ICD (SMD, −0.02; 95% CI, —0.43-0.39).

A diagnosis of ICD is made via a clinical interview with the individual with PD and their caregivers.²³ Questionnaire for ICDs in PD and Questionnaire for ICDs in PD Rating Scale are validated scales with a sensitivity of 96% and 94%, respectively, in identifying ICDs among individuals with PD.²⁴

Although there are no meta-analyses that have evaluated the treatments for ICDs among individuals with PD, treatment recommendations include reducing or even withdrawing DAs as a first-line strategy.²⁵ The use of intrajejunal levodopa that provides continuous drug delivery to the body or using amantadine, which acts as a dopaminergic and glutamatergic modulator, may benefit some individuals with ICD without aggravating motor functions. Limited data also indicate some benefit from valproate, zonisamide, naloxone, apomorphine, and bromocriptine among individuals with ICD. Clozapine may be beneficial for the treatment of refractory ICDs among individuals with PD.²⁶ Although the data are limited, a few studies also recommend subthalamic nucleus deep brain stimulation as a treatment for ICDs.²⁵ Low-frequency repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex has also been noted to be beneficial among individuals with PD and ICBs.²⁷ One randomized controlled trial that compared up to 12 sessions of a cognitive behavior therapy (CBT)-based intervention to a waiting list control condition with standard medical care indicated that ICBs improved significantly in the treatment group when compared with controls (P = .03).²⁸

These studies indicate that discontinuation of DAs and the use of CBT may be first options for treating ICDs/ICBs among individuals with PD. Medications such as clozapine and treatments such as rTMS may be useful among refractory cases of ICDs/ICBs.

Cognitive Impairment

Among individuals with PD, cognitive impairment is one of the major nonmotor symptoms.²⁹ Cognitive impairment presents insidiously among individuals with PD and includes impairments in planning, working memory, executive dysfunction, attention, semantic verbal fluency, and visual spatial ability. Individuals with PD may subsequently develop mild cognitive impairment (MCI), which may progress to dementia. Results of a meta-analysis found that postural-instability-gait disorder (RR, 3.76), hallucinations (RR, 3.09), orthostatic hypotension (RR, 2.98), cerebrovascular disease (RR, 1.52), diabetes (RR, 1.47), obesity (RR, 1.38), cardiac disease (RR, 1.35), and alcohol consumption (RR, 1.32) increase the risk for cognitive impairment among individuals with PD.³⁰

One meta-analysis found that the pooled prevalence of MCI was 40%, with a higher frequency for the multiple domain subtype (31%) of MCI to be seen among individuals with PD.³¹ Risk factors for developing MCI in PD were older age (Hedges g = 0.36), male sex (Hedges g = 0.10), lower levels of education (Hedges g = —0.29), a longer disease duration (Hedges g = 0.18), use of higher LEDD (Hedges g = 0.25), higher Hoehn and Yahr stage (Hedges g = 0.33), higher UPDRS motor scores (Hedges g = 0.40), postural instability/gait difficulty motor subtype vs tremor dominant subtype (46% vs 35%; P <.001), depression (Hedges g = 0.29), apathy (Hedges g = 0.41), and a poorer quality of life (Hedges g = 0.18). One meta-analysis that included data from 39 studies found that within 3 years, 25% of individuals with PD and normal cognition converted to PD-MCI, and 2% converted to dementia.³² Of those with PD-MCI, 20% converted to dementia, while 28% reverted to a state of normal cognitive function. The investigators noted that the conversion rates to MCI and dementia were higher and reversion rates were lower when the follow-up was equal to or longer than 3 years. A meta-analysis revealed that among all the cognitive domains (Hedges g = 0.47), measures of executive functioning (Hedges g = 0.70) predicted the conversion of individuals with PD-MCI to PD dementia (PDD).³³

One meta-analysis found that the global pooled dementia frequency among individuals with PD was 26.3%.³⁴ The pooled frequency of dementia was greater among individuals aged 75 years or older (43.4%), less than or equal to 4 years of education (29.2%), 15 years or longer of PD duration (40.9%), and greater than 3 on the Hoehn and Yahr stage (45.9%). A recent meta-analysis found that the pooled incidence rate of PDD was 4.45 per 100 person-years at risk, equating to a 4.5% annual risk of dementia in a PD-prevalent population.³⁵ The relative risk of PDD was estimated to be 3.25 times greater than in healthy controls. Another meta-analysis found that the development of PDD was positively associated with older age (OR, 1.07), male sex (OR, 1.33), higher UPDRS part III scores (RR, 1.04), presence of hallucinations (OR, 2.47), REM sleep behavior disorder (OR, 8.38), smoking (ever vs never: RR, 1.93), and hypertension (OR, 1.57).³⁶ An inverse association was found between education (RR, 0.94) and the development of PDD. One meta-analysis that included data from 17 studies analyzed the influence of the APOE gene on PDD onset from 3 aspects: 5 genotypes vs ε3/3, ε2+/ε4+ vs ε3/3, and ε4+ vs ε4−, and found that the risk factors for PDD include the genotypes ε3/4 (OR, 1.47) and ε4/4 (OR, 2.93; 95% CI, 1.20-7.14).³⁷ The risk of PDD was 1.61 times greater in ε4+ individuals when compared with ε3/3 individuals (OR, 1.61; P = .0003). Among individuals with PD, the dementia risk of those with ε4+ was 1.72 times greater than that of those with ε4− (OR, 1.72; P <.00001).

It is important to regularly evaluate cognitive functioning among individuals with PD given the prevalence of cognitive impairment among them.³⁸ The presence of a cognitive disorder can be identified using validated screening tools or through a formal neuropsychological assessment. It is also important to complete a full medical examination including laboratory workup to rule out the potential medical causes for cognitive impairment. The International Parkinson and Movement Disorder Society recommends 3 rating scales based on their clinimetric properties to measure global cognitive performance among individuals with PD.³⁹ These 3 scales are the Montreal Cognitive Assessment (MoCA), the Mattis Dementia Rating Scale Second Edition, and the Parkinson’s Disease-Cognitive Rating Scale. The MoCA is the most frequently used cognitive screening tool in clinical practice and research studies among individuals with PD. Available evidence indicates that normed neuropsychological tests across multiple cognitive domains can consistently detect cognitive deficits among individuals with PD, but relative PD performance is significantly affected by the inclusion and the type of healthy controls vs the use of published norms only.⁴⁰ It is important that the selection of tests be done based on the presence of adequate local population norms.

Currently, there are no FDA-approved nonpharmacologic or pharmacologic treatments for MCI among individuals with PD.⁴¹ Preliminary evidence indicates that cognitive training and physical exercise may have short-term benefits on executive functioning among individuals with PD.³⁸ Multidomain computer-based cognitive training at a frequency of 2 or 3 times per week over 3 to 12 weeks may improve executive functions, memory, processing speed, and attention.³⁸ Aerobic exercise, resistance exercise, and combined physical and cognitive training may show short-term benefits on global cognition, processing speed, sustained attention, mental flexibility, and memory among individuals with PD.³⁸

Just oral rivastigmine is FDA approved for the treatment of mild-to-moderate PDD.³⁸ One meta-analysis found that among individuals with PDD, when compared with placebo, CHI treatment improved scores on the Alzheimer Disease Cooperative Study—Clinical Global Impression of Change (P <.0001).⁴² For cognitive function, a pooled estimate of the effect of CHIs on measures of cognitive function showed therapeutic benefit (SMD, —0.34; P <.00001). There was also a positive effect of CHIs on the MMSE (weighted mean difference [WMD], 1.09; P = .0008). For activities of daily living, combined data for the Alzheimer Disease Cooperative Study—Clinical Global Impression of Change and the UPDRS rating scales favored treatment with CHIs (SMD, —0.20; P = .03). For safety and tolerability, those taking a CHI were more likely to experience an adverse event (OR, 1.64; P = .0003) and to drop out (OR, 1.94; P = .0006). Adverse events were more common among those taking rivastigmine (OR, 2.28; P <.0001) but not those taking donepezil (OR, 1.24; P = .25). Tremors (OR, 2.71; P = .002), but not falls (P = .39), were more common in the treatment group but it did not have a significant impact on the UPDRS (total and motor scores, P = .71). Fewer deaths occurred in the treatment group than in the placebo group (OR, 0.28; P = .03).

Another meta-analysis that included data from 10 trials found that CHIs and memantine produced small global effects on clinicians’ global impression of change (WMD, —0.40 to WMD, —0.65).⁴³ However, just CHIs and not memantine improved cognition on the MMSE (WMD, 1.04 to 2.57 vs 0.45). Rivastigmine showed an increased risk of adverse events when compared with placebo (RR, 1.19), although these were mild or moderate, and the risk disappeared on serious adverse events.

A third meta-analysis study that only included participants with PD found that CHIs significantly slowed MMSE decline (MD, —1.123; P = .0010) without any effect on risk of falls (OR, 1.134; P = .681).⁴⁴ The rates of tremors (OR, 2.805; P = .001) and adverse drug reactions (OR, 1.86; P <.0001) were significantly increased in patients receiving CHIs compared with placebo. When compared with placebo, the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (SMD, —0.266; P <.0001), global assessment (SMD, —0.287, P <.0001), and behavioral disturbances (SMD, —0.152; P = .025) improved in the CHI group without any effect on disability (SMD, —0.134; P = .053). There were no significant differences between the 2 groups on the UPDRS part III scores (SMD, 0.054; P = .805). The death rate was reduced in the CHI group when compared with placebo (OR, 0.295; P = .017).

In a fourth meta-analysis, investigators determined that individuals with PDD who received donepezil (SMD, 0.51; P <.00001) or rivastigmine (SMD, 0.45; P <.00001) found benefits on global cognitive scores when compared with placebo.⁴⁵ On the Clinical Global Impressions of Change scale, significant improvements were noted in participants who received rivastigmine when compared with placebo (RR, 1.37). Rivastigmine in PDD provided a significant benefit for tremor when compared with placebo (MD, —2.32; P <.00001). Just individuals treated with rivastigmine experienced significantly more adverse events when compared with placebo (RR, 1.18; P = .0001).

These studies indicate that nonpharmacologic treatments such as cognitive training and physical exercise may have short-term benefits on cognition among individuals with PD. Oral rivastigmine is the only FDA-approved agent for the treatment of mild-to-moderate PDD, although other CHIs may be of benefit among individuals with PDD.

Concluding Thoughts

NPS are seen commonly among individuals with PD. These include depression, apathy, anxiety, ICDs, psychosis, and cognitive impairment including dementia. Despite being common, the NPS are poorly identified and poorly treated among individuals with PD. NPS worsen morbidity and quality of life among individuals with PD. Available evidence indicates benefits for nonpharmacologic treatments, pharmacotherapeutic agents, and for brain stimulation techniques among individuals with PD who have NPS. Earlier identification and appropriate treatment of individuals with PD who have NPS will significantly improve the lives of these individuals and those of their caregivers.

Dr Tampi is professor and chairman of the Department of Psychiatry at Creighton University School of Medicine and Catholic Health Initiatives Health Behavioral Health Services in Omaha, Nebraska. He is also an adjunct professor of psychiatry at Yale School of Medicine, New Haven, Connecticut. Ms Snyder is a medical student at Creighton University School of Medicine, Omaha, NE.

References

1. Dlay JK, Duncan GW, Khoo TK, et al. Progression of neuropsychiatric symptoms over time in an incident Parkinson’s disease cohort (ICICLE-PD). Brain Sci. 2020;10(2):78.

2. Jones S, Torsney KM, Scourfield L, et al. Neuropsychiatric symptoms in Parkinson’s disease: aetiology, diagnosis and treatment. BJPsych Advances. 2020;26(6):333-342.

3. Chendo I, Silva C, Duarte GS, et al. Frequency and characteristics of psychosis in Parkinson’s disease: a systematic review and meta-analysis. J Parkinsons Dis. 2022;12(1):85-94.

4. Fénelon G, Alves G. Epidemiology of psychosis in Parkinson’s disease. J Neurol Sci. 2010;289(1-2):12-17.

5. Goetz CG, Leurgans S, Pappert EJ, et al. Prospective longitudinal assessment of hallucinations in Parkinson’s disease. Neurology. 2001;57(11):2078-2082.

6. Burchill E, Watson CJ, Fanshawe JB, et al. The impact of psychiatric comorbidity on Parkinson’s disease outcomes: a systematic review and meta-analysis. Lancet Reg Health Eur. 2024;39:100870.

7. Pisani S, Gosse L, Wieretilo R, et al. Cognitive and executive impairments in Parkinson’s disease psychosis: a Bayesian meta-analysis. J Neurol Neurosurg Psychiatry. 2024;95(3):277-287.

8. Pisani S, Gunasekera B, Lu Y, et al. Grey matter volume loss in Parkinson’s disease psychosis and its relationship with serotonergic gene expression: a meta-analysis. Neurosci Biobehav Rev. 2023;147:105081.

9. Ravina B, Marder K, Fernandez HH, et al. Diagnostic criteria for psychosis in Parkinson’s disease: report of an NINDS, NIMH work group. Mov Disord. 2007;22(8):1061-1068.

10. Pagan FL, Schulz PE, Torres-Yaghi Y, Pontone GM. On the optimal diagnosis and the evolving role of pimavanserin in Parkinson’s disease psychosis. CNS Drugs. 2024;38(5):333-347.

11. d’Angremont E, Begemann MJH, van Laar T, Sommer IEC. Cholinesterase inhibitors for treatment of psychotic symptoms in Alzheimer disease and Parkinson disease: a meta-analysis. JAMA Neurol. 2023;80(8):813-823.

12. Yunusa I, Rashid N, Seyedin R, et al. Comparative efficacy, safety, and acceptability of pimavanserin and other atypical antipsychotics for Parkinson’s disease psychosis: systematic review and network meta-analysis. J Geriatr Psychiatry Neurol. 2023;36(5):417-432.

13. Srisurapanont M, Suradom C, Suttajit S, et al. Second-generation antipsychotics for Parkinson’s disease psychosis: a systematic review and network meta-analysis. Gen Hosp Psychiatry. 2024;87:124-133.

14. Takamiya A, Seki M, Kudo S, et al. Electroconvulsive therapy for Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2021;36(1):50-58.

15. Bugalho P, Oliveira-Maia AJ. Impulse control disorders in Parkinson’s disease: crossroads between neurology, psychiatry and neuroscience. Behav Neurol. 2013;27(4):547-557.

16. Macías-García P, Rashid-López R, Cruz-Gómez ÁJ, et al. Neuropsychiatric symptoms in clinically defined Parkinson’s disease: an updated review of literature. Behav Neurol. 2022;2022:1213393.

17. Cao L, Xu T, Zhao G, et al. Risk factors of impulsive-compulsive behaviors in PD patients: a meta-analysis. J Neurol. 2022;269(3):1298-1315.

18. Phu AL, Xu Z, Brakoulias V, et al. Effect of impulse control disorders on disability and quality of life in Parkinson’s disease patients. J Clin Neurosci. 2014;21(1):63-66.

19. Santangelo G, Raimo S, Barone P. The relationship between impulse control disorders and cognitive dysfunctions in Parkinson’s disease: a meta-analysis. Neurosci Biobehav Rev. 2017;77:129-147.

20. Liu B, Luo W, Mo Y, et al. Meta-analysis of related factors of impulse control disorders in patients with Parkinson’s disease. Neurosci Lett. 2019;707:134313.

21. Lu HT, Shen QY, Zhao QZ, et al. Association between REM sleep behavior disorder and impulsive-compulsive behaviors in Parkinson’s disease: a systematic review and meta-analysis of observational studies. J Neurol. 2020;267(2):331-340.

22. Santangelo G, Raimo S, Cropano M, et al. Neural bases of impulse control disorders in Parkinson’s disease: a systematic review and an ALE meta-analysis. Neurosci Biobehav Rev. 2019;107:672-685.

23. Weintraub D, Claassen DO. Impulse control and related disorders in Parkinson’s disease. Int Rev Neurobiol. 2017;133:679-717.

24. Weintraub D, Hoops S, Shea JA, et al. Validation of the questionnaire for impulsive-compulsive disorders in Parkinson’s disease. Mov Disord. 2009;24(10):1461-1467.

25. Zhang JF, Wang XX, Feng Y, et al. Impulse control disorders in Parkinson’s disease: epidemiology, pathogenesis and therapeutic strategies. Front Psychiatry. 2021;12:635494.

26. Bonfils NA, Benyamina A, Aubin HJ, Luquiens A. Clozapine use for refractory impulse control disorders in Parkinson’s disease: a case report. Psychopharmacology (Berl). 2015;232(19):3677-3679.

27. Nardone R, De Blasi P, Höller Y, et al. Repetitive transcranial magnetic stimulation transiently reduces punding in Parkinson’s disease: a preliminary study. J Neural Transm (Vienna). 2014;121(3):267-274.

28. Okai D, Askey-Jones S, Samuel M, et al. Trial of CBT for impulse control behaviors affecting Parkinson patients and their caregivers. Neurology. 2013;80(9):792-799.

29. Fang C, Lv L, Mao S, et al. Cognition deficits in Parkinson’s disease: mechanisms and treatment. Parkinsons Dis. 2020;2020:2076942.

30. Guo Y, Xu W, Liu FT, et al. Modifiable risk factors for cognitive impairment in Parkinson’s disease: a systematic review and meta-analysis of prospective cohort studies. Mov Disord. 2019;34(6):876-883.

31. Baiano C, Barone P, Trojano L, Santangelo G. Prevalence and clinical aspects of mild cognitive impairment in Parkinson’s disease: a meta-analysis. Mov Disord. 2020;35(1):45-54.

32. Saredakis D, Collins-Praino LE, Gutteridge DS, et al. Conversion to MCI and dementia in Parkinson’s disease: a systematic review and meta-analysis. Parkinsonism Relat Disord. 2019;65:20-31.

33. Wallace ER, Segerstrom SC, van Horne CG, et al. Meta-analysis of cognition in Parkinson’s disease mild cognitive impairment and dementia progression. Neuropsychol Rev. 2022;32(1):149-160.

34. Severiano E Sousa C, Alarcão J, Pavão Martins I, Ferreira JJ. Frequency of dementia in Parkinson’s disease: a systematic review and meta-analysis. J Neurol Sci. 2022;432:120077.

35. Gibson LL, Weintraub D, Lemmen R, et al. Risk of dementia in Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2024;39(10):1697-1709.

36. Xu Y, Yang J, Shang H. Meta-analysis of risk factors for Parkinson’s disease dementia. Transl Neurodegener. 2016;5:11.

37. Pang S, Li J, Zhang Y, Chen J. Meta-analysis of the relationship between the APOE gene and the onset of Parkinson’s disease dementia. Parkinsons Dis. 2018;2018:9497147.

38. Aarsland D, Batzu L, Halliday GM, et al. Parkinson disease-associated cognitive impairment. Nat Rev Dis Primers. 2021;7(1):47.

39. Skorvanek M, Goldman JG, Jahanshahi M, et al; members of the MDS Rating Scales Review Committee. Global scales for cognitive screening in Parkinson’s disease: critique and recommendations. Mov Disord. 2018;33(2):208-218.

40. Hoogland J, van Wanrooij LL, Boel JA, et al; IPMDS Study Group. Detecting mild cognitive deficits in Parkinson’s disease: comparison of neuropsychological tests. Mov Disord. 2018;33(11):1750-1759.

41. Sun C, Armstrong MJ. Treatment of Parkinson’s disease with cognitive impairment: current approaches and future directions. Behav Sci (Basel). 2021;11(4):54.

42. Rolinski M, Fox C, Maidment I, McShane R. Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson’s disease dementia and cognitive impairment in Parkinson’s disease. Cochrane Database Syst Rev. 2012;2012(3):CD006504.

43. Wang HF, Yu JT, Tang SW, et al. Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson’s disease, Parkinson’s disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis. J Neurol Neurosurg Psychiatry. 2015;86(2):135-143.

44. Pagano G, Rengo G, Pasqualetti G, et al. Cholinesterase inhibitors for Parkinson’s disease: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2015;86(7):767-773.

45. Meng YH, Wang PP, Song YX, Wang JH. Cholinesterase inhibitors and memantine for Parkinson’s disease dementia and Lewy body dementia: a meta-analysis. Exp Ther Med. 2019;17(3):1611-1624.