What can biomarkers tell us about cognition in Parkinson's disease?

Abstract

Cognitive decline is common in Parkinson's disease (PD), even in the early motor stage, and this non-motor feature impacts quality of life and prognosis tremendously. In this article, we discuss marker candidates for cognitive decline in PD from different angles, including functional and structural imaging techniques, biological fluid markers in cerebrospinal fluid, and blood genetic predictors, as well as gait as a surrogate marker of cognitive decline. Specifically, imaging-based markers of cognitive impairment in PD include cortical atrophy, reduced cortical metabolism, loss of cortical cholinergic and frontal dopaminergic function, as well as an increased cortical amyloid load. Reduced β-amyloid(1-42) in cerebrospinal fluid and lower plasma levels of epidermal growth factor are predictors for cognitive decline in PD. In addition, genetic variation in the apolipoprotein E (APOE), catechol-O-methyltransferase (COMT), microtubule-associated protein tau (MAPT), and glucocerebrosidase (GBA) genes may confer risk for cognitive impairment in PD; and gait disturbance may also indicate an increased risk for dementia. Other marker candidates have been proposed and are discussed. All of the current studies are hampered by gaps in our knowledge about the molecular causes of cognitive decline, which will have to be considered in future biomarker studies.

Decrease in Aβ42 predicts dopa-resistant gait progression in early Parkinson disease

“…Evidence that motor changes precede cognitive changes is common in older adults 38 and has fueled an interest in the role of gait as a clinical biomarker of cognitive decline. 6 The shared pathologic mechanisms of gait and cognitive decline support the potential of gait characteristics as clinical biomarkers of cognitive decline in PD 14,39 and work is under way investigating this.…”

“…5 CSF proteins (e. g., b-amyloid [Ab] 40 and Ab42; total and p-tau 181 ), traditionally biomarkers of dementia and dementia risk, [6][7][8][9] have also been implicated in motor impairment, highlighting a role for pathologic protein accumulation other than Lewy body and PD-specific a-synuclein (aSyn). Crosssectional studies in early and advanced PD show an association between CSF biomarkers and postural instability and gait (PIGD) phenotype.…”

Increase of EEG Spectral Theta Power Indicates Higher Risk of the Development of Severe Cognitive Decline in Parkinson’s Disease after 3 Years

“…The risk of dementia is about 80% for the patients living for more than 20 years with PD (Hely et al, 2008). Early and correct identification of the patients with the risk of severe cognitive decline is a challenging problem of neurology, which has led to the suggestion of various markers of cognitive decline in PD (Mollenhauer et al, 2014). Quantitative electroencephalography (qEEG) – digital processing of EEG recordings to obtain numerical and graphical data – showed that the power (the square of amplitudes of electrical activity) of the brain in PD patients with cognitive impairment is increased in the frequency range below 8 Hz, and decreased in the range above 8 Hz (Caviness et al, 2007; Fonseca et al, 2009; Babiloni et al, 2011).…”

Is There Any Relationship between Apolipoprotein E Polymorphism and Idiopathic Parkinson’s Disease?

“…Forty-two percent of patients with Parkinson's disease showed senile plaques and neurofibrillary tangles in the cerebral cortex [14]. Fourth, the level of cerebrospinal biomarkers such as Amyloid-beta and Tau protein is changed in both degenerative diseases and the levels have a correlation with the severity of cognitive impairment in Parkinson's disease [15]. Pathological studies suggest two kinds of pathological changes related to cognitive decline.…”