Apolipoprotein E (ApoE) is a vital component of several lipoproteins and plays a major role in lipid metabolism. APOE gene comprises of three alleles determined by two single nucleotide polymorphisms (rs429358 and rs7412) resulting in the protein isoforms, among which ApoE4 is a confirmed risk factor for Alzheimer's Disease. However, the impact of APOE genotypes on Parkinson's Disease Dementia (PDD) is still inconclusive. The PDD diagnostic criteria are very inconsistent, and could be complemented with genetic factors. Our study covers a total of 237 patients diagnosed with Parkinson's Disease (PD) according to UK PD Brain Bank criteria, who were classified as subjects with (PDD, n equals 73) and without (nPDD, n equals 164) dementia, using neuropsychological assessment tests. TaqMan real-time PCR assays were used to determine APOE allele. No statistically significant differences in APOE alleles frequencies between nPDD and PDD patients have been observed. The study results revealed that the APOE polymorphism is not associated with cognitive status in PD patients.

Dementia is one of the most disabling non-motor symptoms in Parkinson’s disease (PD). Unlike in Alzheimer’s disease, the vascular pathology in PD is less documented. Due to the uncertain role of commonly investigated metabolic or vascular factors, e.g., hypertension or diabetes, other factors corresponding to PD dementia have been proposed. Associated dysautonomia and dopaminergic treatment seem to have an impact on diurnal blood pressure (BP) variability, which may presumably contribute to white matter hyperintensities (WMH) development and cognitive decline. We aim to review possible vascular and metabolic factors: Renin-angiotensin-aldosterone system, vascular endothelial growth factor (VEGF), hyperhomocysteinemia (HHcy), as well as the dopaminergic treatment, in the etiopathogenesis of PD dementia. Additionally, we focus on the role of polymorphisms within the genes for catechol-O-methyltransferase (COMT), apolipoprotein E (APOE), vascular endothelial growth factor (VEGF), and for renin-angiotensin-aldosterone system components, and their contribution to cognitive decline in PD. Determining vascular risk factors and their contribution to the cognitive impairment in PD may result in screening, as well as preventive measures.

Parkinson’s disease (PD) is the second most common neurodegenerative disease characterised by both motor- and non-motor symptoms, including cognitive impairment. The aetiopathogenesis of PD, as well as its protective and susceptibility factors, are still elusive. Neuroprotective effects of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors—statins—via both cholesterol-dependent and independent mechanisms have been shown in animal and cell culture models. However, the available data provide conflicting results on the role of statin treatment in PD patients. Moreover, cholesterol is a vital component for brain functions and may be considered as protective against PD. We present possible statin effects on PD under the hypothesis that they may depend on the HMG-CoA reductase gene (HMGCR) variability, such as haplotype 7, which was shown to affect cholesterol synthesis and statin treatment outcome, diminishing possible neuroprotection associated with HMG-CoA reductase inhibitors administration. Statins are among the most prescribed groups of drugs. Thus, it seems important to review the available data in the context of their possible neuroprotective effects in PD, and the HMG-CoA reductase gene’s genetic variability.

Dementia in advanced Parkinson's Disease (PD) is a fatal milestone resulting in reduced life expectancy and nursing home placement. Cognitive impairment and cardiovascular dysautonomia are common and debilitating non-motor symptoms that frequently coexist in PD since the early stages and progress in subsequent years.In particular, blood pressure (BP) abnormalities, including orthostatic hypotension (OH), supine hypertension (SH) and the loss of nocturnal BP fall (non-dipping) in PD have been associated with cognitive deterioration. They usually have multifactorial aetiology, including neuronal (central and peripheral) mechanisms and concomitant intake of medications. BP abnormalities can influence cognition in many ways, including repeated cerebral hypoperfusion leading to cerebral ischaemic lesions, higher burden of white matter hyperintensities, and possible impact on neurodegenerative process in PD. They are often asymptomatic and remain unrecognised, hence 24-hour ambulatory BP monitoring is recommended in patients with clinical symptoms of dysautonomia. Management is challenging and should address the multifactorial nature of BP disturbances. The aim of this review was to present the state of current knowledge regarding the possible relationship between cardiovascular dysautonomia and cognition in PD, its diagnosis and treatment.

The present study investigated associations of two functional MMP12 polymorphisms with PD risk and cognitive impairment in PD. A total of 478 study subjects (241 PD and 237 age and sex matched controls) were included in the study. UPDRS score, Hoehn-Yahr staging and Schwab-England scale were used to assess motor abilities and activity during daily life. All patients were classified into groups with dementia (PDD, n=72) and without dementia (nPDD, n=159) based on the neuropsychological assessment. The two most common functional single nucleotide polymorphisms (SNPs) in MMP12 gene were determined using TaqMan real-time PCR assays. Frequencies of evaluated MMP12 rs2276109 alleles and genotypes were similar in PD and the controls, whereas rs652438G allele genotypes were significantly more frequent among healthy individuals (p=0.013, OR 0.47 (0.26-0.85). The rs2276109 and rs652438 allele and genotype frequencies were not associated with dementia in PD patients. The current results suggest that MMP12 rs652438 but not MMP12 rs2276109 may affect the risk for PD, as the minor G allele genotypes might be a protective factor.