CSF amyloid β 1-42 predicts cognitive decline in Parkinson disease

Abstract

Objective: Cognitive decline associated with Parkinson disease (PD) is common and highly disabling. Biomarkers that help identify patients at risk for cognitive decline would be useful additions to the clinical management of the disease. Methods:A total of 45 patients with PD were enrolled in this prospective cohort study and had at least 1 yearly longitudinal follow-up evaluation. CSF was collected at baseline and cognition was assessed at baseline and follow-up visits using the Mattis Dementia Rating Scale (DRS-2). CSF was tested for amyloid ␤ 1-42 (A␤ 1-42 ), p-tau 181p , and total tau levels using the Luminex xMAP platform. Mixed linear models were used to test for associations between baseline CSF biomarker levels and change in cognition over time.Results: Lower baseline CSF A␤ 1-42 was associated with more rapid cognitive decline. Subjects with CSF A␤ 1-42 levels Յ192 pg/mL declined an average of 5.85 (95% confidence interval 2.11-9.58, p ϭ 0.002) points per year more rapidly on the DRS-2 than subjects above that cutoff, after adjustment for age, disease duration, and baseline cognitive status. CSF total tau and p-tau 181p levels were not significantly associated with cognitive decline. Conclusions:

Homovanillic acid in CSF of mild stage Parkinson's disease patients correlates with motor impairment

“…So far, this sort of repeated samples is usually not permitted; however, few recent investigations utilized longitudinal measurements (Siderowf et al, 2010;Hall et al, 2015), obtained at baseline and after 3 years, in order to study if changes of CSF biomarkers correlate with motor progression.…”

CFS Biomarkers in Parkinson’s Disease

“…Authors showed also a significant association between CSF levels of A 1-42 , A 1-40 , A 1-38 and memory impairment. A recent prospective study in a cohort of 45 PD patients with 1-year follow-up showed that lower levels of A 1-42 at baseline were associated with a more rapid cognitive decline (Siderowf et al, 2010). Another recent study reported an association between low levels of A 1-42 levels in 22 non-demented PD patients and worse performance at Digit Symbol test .…”

“…The spreading of Lewy body pathology to neocortical regions altogether with AD-type pathology in terms of -amyloid deposits, have been implicated in the pathogenesis of cognitive decline in PD (Braak et al, 2005;Ballard et al, 2006), suggesting an interplay between synucleinopathies and tauopathies. Recently, a growing amount of investigations in PD has focused on CSF biomarkers traditionally used in AD, namely -amyloid 1-42 (A 1-42 ), total tau, hyperphosphorylated tau, in order to improve the ability to detect risk for cognitive impairment and dementia (Sjögren et al, 2002;Mollenhauer et al, 2006;Parnetti et al, 2008;Compta et al, 2009;Alves et al, 2010;Siderowf et al, 2010;Montine et al, 2010;Leverenz et al, 2011) (table 2). Tau protein, a microtubule associated protein, in its phosphorylated form represents the major component of the neurofibrillary tangles (Grundke-Iqbal et al, 1986).…”

“…Studies report normal CSF levels of tau and phosphorylated tau in PD (Blennow et al, 1995;Parnetti et al, 2008;Alves et al, 2010;, whereas unchanged or slightly decreased levels of A 1-42 have been reported (Sjögren et al, 2002;Mollenhauer et al, 2006;Bibl et al, 2006;Parnetti et al, 2008;Compta et al, 2009;Alves et al, 2010;Siderowf et al, 2010;Montine et al, 2010;Leverenz et al, 2011;Shi et al, 2011). More recently, several studies have been published reporting a possible association between low A 1-42 levels and cognitive impairment in PD (Compta et al, 2009;Alves et al, 2010;Siderowf et al, 2010;Montine et al, 2010;Leverenz et al, 2011). Lower levels of CSF A 1-42 were found in 20 PD-patients with dementia compared to 20 PDpatients and 30 controls, whereas higher concentrations of CSF tau and phosphorylated tau were associated with impaired memory and naming, suggesting an underlying AD pathology in PDD (Compta et al, 2009).…”

Clinically Useful Biomarkers for Parkinson’s Disease

“…In PD, studies have shown normal or decreased levels of CSF Aβ42 in PD [32]. Low levels of Aβ42 in non-demented PD patients have been shown to be associated with future cognitive decline and an increased risk of developing dementia and memory impairment [33].…”