Table 6. Details of included studies.

Aβ: Amyloid-β; Aβ1-42: Amyloid-β 1-42; α-syn: Alpha-synuclein; AD: Alzheimer's disease; AQT: A quick test of cognitive speed; CSF: Cerebrospinal fluid; HC: Healthy control; LB: Lewy body; NfL: Neurofilament light; PD: Parkinson's disease; PDD: Parkinson's disease dementia; PET: Positron emission tomography; Tau: Tubulin-associated unit; p-Tau: Phosphorylated Tau; t-tau: Total Tau; TUG: Timed up and go; UPDRS III: Unified Parkinson's disease rating scale part III; YKL-40: Chitinase-3-like protein 1 (CHI3L1)

Author and year of publication	Type of the study	Purpose of the study and biomarker studied	Number of participants	Results	Conclusions
Baek et al. 2021 [3]	Cohort study	Predicting long-term temporal effects of CSF α-syn, Aβ, t-Tau, p-Tau, and serum NfL by observing and integrating the function between baseline levels and annual changes.	578	Concentrations of α-syn decreased exponentially while t-Tau and p-Tau increased prior to the onset of motor symptoms. The rates of change were higher in those diagnosed with cognitive impairment.	Amyloid burden and cognitive impairment may correlate with changes in biomarker levels. The rapid growth of LB- and AD-type pathologies may feature early cognitive decline. Vulnerability to LB pathologies, neuroaxonal damage, and cognitive impairment was apparent in PD patients with low Aβ1-42. Amyloid-lowering therapy may be useful in delaying pathological progression and cognitive decline in PD.
Hall et al. 2016 [6]	Cohort study	Investigating the use of CSF biomarkers to predict the progression of motor and cognitive decline in patients with PD	111	Over two years, increased levels of α-syn and p-Tau were linked to motor function and cognitive decline as tested with Hoehn and Yahr, UPDRS III, TUG, and AQT.	Over the course of 2 years, evidence indicates an association of cognitive and motor decline with increased levels of α-syn. It's believed that α-syn might act as a biomarker for more intense synaptic degeneration in those with PD.
Hall et al. 2015 [5]	Cohort study	Investigating the changes of CSF Tau protein and α-syn correlate with the progression of cognitive and motor decline in PD.	84	A significant correlation between concentrations of α-syn and Tau in CSF was observed. Levels of α-syn, t-Tau, and p-Tau increased over two years in the PD group whereas there were no observable changes in the HCs. Those with long disease duration exhibited increases in α-syn and Tau levels. The faster motor decline is linked to an increase in p-Tau over two years.	Over the course of two years, CSF levels of α-syn, Tau proteins, NfL, and YKL-40 increased in patients with PD. α-syn and Tau levels, in particular, remain stable in the early phases of PD but increase as the disease progresses. It is suspected that α-syn levels will increase further with neurodegeneration over time.
Kang et al. 2013 [4]	Cross-sectional study	Observing and analyzing the baseline characteristics and relationship to the clinical uses of CSF Tau proteins and α-syn as biomarkers in HCs and drug-naive patients in the early stages of PD.	102	In comparison to HCs, those with PD showed decreased levels of t-Tau, p-Tau, and α-syn. There was a significant correlation between α-syn and Tau levels.	Aβ1-42, t-Tau, p-Tau181, and α-syn levels in CSF can be used to identify early stages of PD when compared to HCs while also reflecting the various clinical features of PD.
Leaver and Poston 2015 [1]	Systematic review	Analyzing the use of CSF protein as biomarkers for prediction of cognitive impairment.	1218	There is limited evidence of the usefulness of Tau protein as a biomarker for predicting PD. Concentrations of α-syn have better potential, however, evidence for the protein as a predictive biomarker is mixed.	Biomarkers in CSF are only one of many under consideration in the diagnosis and prognosis of PDD. Used in combination with genetics, brain network connectivity, and biochemical changes, CSF biomarkers have the potential to predict cognitive decline in PD patients. When also considering demographic and clinical risk, those with the highest risk of PDD can be identified early.
Myers et al. 2022 [2]	Cohort study	Examining the predictive qualities of certain proteins in regards to longitudinal cognitive decline in PD.	204	As predictive biomarkers, α-syn and Tau served poorly while others such as amyloid-β were more effective.	PET scans of CSF levels of B-amyloid appear predictive of cognitive decline. CSF levels of α-syn and Tau protein seemed to indicate cognitive decline.
Pagan et al. 2020 [16]	Randomized controlled trial	Analyzing the effects of nilotinib in exploratory biomarkers in patients with PD.	75	The 150-mg group exhibited decreases in α-syn oligomers and p-Tau concentrations. The 300-mg group showed only a decrease in α-syn levels.	Trials of treatment with nilotinib yielded feasibly safe results. Nilotinib was detectable in CSF and exploratory biomarkers showed a response.
Pagan et al. 2016 [7]	Randomized controlled trial	Assessing the safety and feasibility of nilotinib in the treatment of PD.	75	Doses of 150 mg and 300 mg of nilotinib per day have shown minimal serious adverse effects potentially providing a safe treatment to those with advanced PD.	Collectively, observations indicate the potential of nilotinib as a potential treatment against PDD which warrants further study with larger, randomized, double-blind, placebo-controlled trials.
Skogseth et al. 2015 [15]	Cohort study	Examining the link between CSF biomarkers and PDD and comparing the differences in biomarker concentrations in CSF between patients with PDD and those with only PD	603	Reduced performance on the executive-attention domain and the composite cognition factor in the whole PD group has been linked to reduced concentrations of α-syn.	α-syn pathology is suspected to contribute to cognitive impairment in PD due to an association of concentrations of the protein in CSF with cognition.
Wang et al. 2019 [8]	Narrative review	Studying the pathological states of α-syn and analyzing the antibodies that recognize monomers or oligomers of α-syn.		Antibodies can be used to mark specific posttranslational modifications of α-syn for termination which, due to the protein's contribution towards Tau hyperphosphorylation, may also reduce concentrations of p-Tau.	Antibodies targeting α-syn have the potential to treat PD, however since α-syn is diverse, no antibody can target all post-translational modifications of the protein. Additionally, immunotherapy trials have, thus far, been restricted to the laboratory. Nonetheless, recent interest has sparked studies into more targeted treatments.