Monoamine neurotransmitters play essential roles in the regulation of arousal and sleep. Impaired metabolism of monoamine neurotransmitters could result in the accumulation of neurotoxic aldehyde metabolites and, hence, neuronal degeneration. Aldehyde dehydrogenases play an important role in the metabolism of the neurotoxic aldehyde metabolites, including the aldehyde metabolites of dopamine, serotonin, and noradrenaline. Deficient aldehyde dehydrogenase 2 (ALDH2) has been suggested to result in the accumulation of these biogenic aldehydes. An ALDH2 single nucleotide polymorphism (SNP), rs671 (A), results in significantly reduced ALDH2 enzyme activity. A total of 83 Parkinson’s disease (PD) patients were recruited in this study. In addition to the genotypes of rs671, the patients were assessed with the PD sleep scale-2nd version (PDSS-2) and the Epworth sleepiness scale (ESS) for symptoms of daytime and nocturnal sleep disturbances. The patients carrying rs671 (A) had more frequent dozing while lying down to rest in the afternoon (ESS item5) (F = 7.308, p = 0.008) than the rs671 (GG) patients. The patients with rs671 (A) reported a trend toward more frequent difficulty staying asleep than the patients with rs671 (GG). (F = 3.278, p = 0.074). The results indicate that patients carrying allele rs671 (A) are more likely to experience impairment in the regulation of arousal and sleep. The results also support the hypothesis that the accumulation of neurotoxic monoamine neurotransmitter aldehyde metabolites secondary to reduced ALDH2 enzyme activity may cause more severe monoaminergic neuronal loss and, hence, more severe symptoms in the regulation of wakefulness and sleep.

Background and Purpose: Small vessel disease (SVD) imaging markers are related to ischemic and hemorrhage stroke and to cognitive dysfunction. This study aimed to clarify the relationship between SVD imaging markers and subcortical vascular dementia in severe SVD burden.Methods: A total of 57 subjects with multiple lobar cerebral microbleeds (CMBs) and four established SVD imaging markers were enrolled from the dementia and stroke registries of a single center. Visual rating scales that are used to semi-quantify SVD imaging changes were analyzed individually and compositely to make correlations with cognitive domains and subcortical vascular dementia.Results: Dementia group had higher subcortical and total white matter hyperintensities (WMHs) and SVD composite scores than non-dementia group. Individual imaging markers correlated differently with one another and had distinct cognitive correlations. After adjusting for demographic factors, multivariate logistic regression indicated associations of subcortical WMHs (odds ratio [OR] 2.03, CI 1.24–3.32), total WMHs (OR 1.43, CI 1.09–1.89), lacunes (OR 1.18, CI 1.02–1.35), cerebral amyloid angiopathy-SVD scores (OR 2.33, CI 1.01–5.40), C₁ scores (imaging composite scores of CMB and WMH) (OR 1.41, CI 1.09–1.83), and C₂ scores (imaging composite scores of CMB, WMH, perivascular space, and lacune) (OR 1.38, CI 1.08–1.76) with dementia.Conclusions: SVD imaging markers might have differing associations with cognitive domains and dementia. They may provide valuable complementary information in support of personalized treatment planning against cognitive impairment, particularly in patients with a heavy SVD load.

(1) Background: The correlation between dysosmia with quality of life (QoL) in patients with PD was rarely reported. The study aimed to examine the effect of dysosmia on motor function and QoL in PD. (2) Methods: This cross-sectional study, performed between October 2016 and February 2021, recorded the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT), the Montreal Cognitive Assessment (MoCA), the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS UPDRS), and the 39-item Parkinson’s Disease Questionnaire (PDQ-39) in patients with PD. UPSIT = 19 was applied to separate the total anosmia and non-anosmia groups. (3) Results: 243 patients with PD were recruited. The total anosmia group had higher MDS UPDRS total, part II, and part III scores than the non-anosmia group. They also had worse scores on the dimensions of activities of daily living (ADL) and cognition of the PDQ-39 than the non-anosmia group. The UPSIT score correlated MDS UPDRS part III score (p < 0.0001), PDQ-39 ADL quartile (p = 0.0202), and Dopamine transporter scan (p = 0.0082) in the linear regression. (4) Conclusions: Dysosmia in PD predicted a phenotype with defective motor function, ADL, and cognition QoL. The findings supported the olfactory transmission of α-synuclein to the cortices, substantia nigra.