In vivo cholinergic basal forebrain atrophy predicts cognitive decline in de novo Parkinson’s disease

The role of cerebrospinal fluid (CSF) biomarkers such as CSF α-synuclein and CSF tau in predicting cognitive decline in Parkinson’s disease (PD) continues to be inconsistent. Here, using a cohort of de novo PD patients with preserved cognition from the Parkinson’s Progression Markers Initiative (PPMI), we show that the SNCA rs356181 single nucleotide polymorphism (SNP) modulates the effect of these CSF biomarkers on cortical thinning. Depending on this SNP’s genotype, cortical atrophy was associated with either higher or lower CSF biomarker levels. Additionally, this SNP modified age-related atrophy. Importantly, the integrity of the brain regions where this phenomenon was observed correlated with cognitive measures. These results suggest that this genetic variation of the gene encoding the α-synuclein protein, known to be involved in the development of PD, also interferes in its subsequent neurodegeneration. Overall, our findings could shed light on the so far incongruent association of common CSF biomarkers with cognitive decline in PD.

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White Matter Hyperintensities and Cognitive Decline in de Novo Parkinson’s Disease Patients

10.1101/230896 ◽

2017 ◽

Author(s):

Mahsa Dadar ◽

Yashar Zeighami ◽

Yvonne Yau ◽

Seyed-Mohammad Fereshtehnejad ◽

Josefina Maranzano ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

White Matter ◽

Cognitive Decline ◽

White Matter Hyperintensities ◽

De Novo ◽

Cognitive Test ◽

Cortical Thinning

AbstractObjectiveWhite Matter Hyperintensities (WMHs) are associated with cognitive decline in normative aging and Alzheimer’s disease. However, the pathogenesis of cognitive decline in Parkinson’s disease (PD) is not directly related to vascular causes, and therefore the role of WMHs in PD remains unclear. If WMH has a higher impact on cognitive decline in PD, vascular pathology should be assessed and treated with a higher priority in this population. Here we investigate whether WMH leads to increased cognitive decline in PD, and if these effects relate to cortical thinningMethodsTo investigate the role of WMHs in PD, it is essential to study recently-diagnosed/non-treated patients.De novoPD patients and age-matched controls (NPD=365,NControl=174) with FLAIR/T2-weighted scans at baseline were selected from Parkinson’s Progression Markers Initiative (PPMI). WMHs and cortical thickness were measured to analyse the relationship between baseline WMHs and future cognitive decline (follow-up:4.09±1.14 years) and cortical thinning (follow-up:1.05±0.10 years).ResultsHigh WMH load (WMHL) at baseline in PD was associated with increased cognitive decline, significantly more than i) PDs with low WMHL and ii) controls with high WMHL. Furthermore, PD patients with higher baseline WMHL showed more cortical thinning in right frontal lobe than subjects with low WMHL. Cortical thinning of this region also predicted decline in performance on a cognitive test.InterpretationPresence of WMHs inde novoPD patients predicts greater future cognitive decline and cortical thinning than in normal aging. Recognizing WMHs as a potential predictor of cognitive deficit in PD provides an opportunity for timely interventions.

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The NGF superfamily of neurotrophins: Potential treatment for Alzheimer's and Parkinson's disease

Behavioral and Brain Sciences ◽

10.1017/s0140525x00037432 ◽

1995 ◽

Vol 18 (1) ◽

pp. 63-65 ◽

Cited By ~ 1

Author(s):

Elliott J. Mufson ◽

Teresa Sobreviela

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Forebrain ◽

Tyrosine Kinase Receptors ◽

Potential Treatment ◽

Neuron Degeneration ◽

Cholinergic Basal Forebrain ◽

The Family ◽

Substantia Nigra Neuron ◽

Tissue Grafts

AbstractStein & Glasier suggest embryonic neural tissue grafts as a potential treatment strategy for Alzheimer's and Parkinson's disease. As an alternative, we suggest that the family of nerve growth factor-related neurotrophins and their trk (tyrosine kinase) receptors underlie cholinergic basal forebrain (CBF) and dopaminergic substantia nigra neuron degeneration in these diseases, respectively. Therefore, treatment approaches for these disorders could utilize neurotrophins.

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White matter hyperintensities are linked to future cognitive decline in de novo Parkinson's disease patients

NeuroImage Clinical ◽

10.1016/j.nicl.2018.09.025 ◽

2018 ◽

Vol 20 ◽

pp. 892-900 ◽

Cited By ~ 27

Author(s):

Mahsa Dadar ◽

Yashar Zeighami ◽

Yvonne Yau ◽

Seyed-Mohammad Fereshtehnejad ◽

Josefina Maranzano ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

White Matter ◽

Cognitive Decline ◽

White Matter Hyperintensities ◽

De Novo

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Serum Neurofilament Dynamics Predicts Cognitive Progression in de novo Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-212535 ◽

2021 ◽

pp. 1-11

Author(s):

Ling-Zhi Ma ◽

Can Zhang ◽

Han Wang ◽

Ya-Hui Ma ◽

Xue-Ning Shen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Decline ◽

Cox Regression ◽

De Novo ◽

Rate Of Change ◽

Neurofilament Light ◽

Baseline Serum ◽

Axon Damage ◽

High Concentrations

Background: Neurofilament light (NfL) can reflect the extent of neuron/axon damage, thus providing an opportunity to examine the severity and progression of the diseases with such damage. Objective: Whether serum NfL can be used as an indicator to monitor the cognitive progress of de novo Parkinson’s disease (PD) remains unclear. Methods: In this research, 144 healthy controls and 301 de novo PD patients from Parkinson’s Progression Markers Initiative (PPMI) were recruited. Linear mixed effects models were used to examine the associations of baseline/longitudinal serum NfL with cognitive decline. Cox regression was used to detect cognitive progression in PD participants. Results: We found PD patients had higher serum NfL than controls at baseline (p = 0.031), and NfL increase was faster in PD group (p < 0.001). Both baseline serum NfL and its rate of change predicted measurable cognitive decline in early PD (MoCA, β= –0.014, p < 0.001; β= –0.002, p < 0.001, respectively). Additionally, we observed that NfL levels were also able to predict progression in different diagnostic groups and Amyloid- PD and Amyloid+PD groups. After an average follow-up of 6.37±1.84 years, the baseline NfL of the third tertile of high concentrations was associated with a future high risk of PD dementia (adjusted HR 6.33, 95% CI 2.62–15.29, p < 0.001). Conclusion: In conclusion, our results indicated that the serum NfL concentration could function as an easily accessible biomarker to monitor the severity and progression of cognitive decline in PD.

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Latent Cognitive Phenotypes in De Novo Parkinson’s Disease: A Person-Centered Approach

Journal of the International Neuropsychological Society ◽

10.1017/s1355617717000406 ◽

2017 ◽

Vol 23 (7) ◽

pp. 551-563 ◽

Cited By ~ 3

Author(s):

Denise R. LaBelle ◽

Ryan R. Walsh ◽

Sarah J. Banks

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Decline ◽

Latent Class ◽

De Novo ◽

Demographic Data ◽

Functional Independence ◽

Cognitive Change ◽

Cognitive Profiles ◽

Consistent Performance

AbstractObjectives: Cognitive impairment is an important aspect of Parkinson’s disease (PD), but there is considerable heterogeneity in its presentation. This investigation aims to identify and characterize latent cognitive phenotypes in early PD. Methods: Latent class analysis, a data-driven, person-centered, cluster analysis was performed on cognitive data from the Parkinson’s Progressive Markers Initiative baseline visit. This analytic method facilitates identification of naturally occurring endophenotypes. Resulting classes were compared across biomarker, symptom, and demographic data. Results: Six cognitive phenotypes were identified. Three demonstrated consistent performance across indicators, representing poor (“Weak-Overall”), average (“Typical-Overall”), and strong (“Strong-Overall”) cognition. The remaining classes demonstrated unique patterns of cognition, characterized by “Strong-Memory,” “Weak-Visuospatial,” and “Amnestic” profiles. The Amnestic class evidenced greater tremor severity and anosmia, but was unassociated with biomarkers linked with Alzheimer’s disease. The Weak-Overall class was older and reported more non-motor features associated with cognitive decline, including anxiety, depression, autonomic dysfunction, anosmia, and REM sleep behaviors. The Strong-Overall class was younger, more female, and reported less dysautonomia and anosmia. Classes were unrelated to disease duration, functional independence, or available biomarkers. Conclusions: Latent cognitive phenotypes with focal patterns of impairment were observed in recently diagnosed individuals with PD. Cognitive profiles were found to be independent of traditional biomarkers and motoric indices of disease progression. Only globally impaired class was associated with previously reported indicators of cognitive decline, suggesting this group may drive the effects reported in studies using variable-based analysis. Longitudinal and neuroanatomical characterization of classes will yield further insight into the evolution of cognitive change in the disease. (JINS, 2017, 23, 551–563)

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Potential Sex-Specific Effects of Apolipoprotein E ɛ4 on Cognitive Decline in Early Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-202288 ◽

2020 ◽

pp. 1-9

Author(s):

Ryul Kim ◽

Sangmin Park ◽

Dallah Yoo ◽

Young Ju Suh ◽

Jin-Sun Jun ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Decline ◽

Apolipoprotein E ◽

De Novo ◽

Sensitivity Analyses ◽

Specific Effects ◽

E4 Allele ◽

Generalized Linear Mixed Effects

Background/Objective: To compare the longitudinal trajectories of cognition according to the presence of the apolipoprotein E (APOE) ɛ4 allele in male and female Parkinson’s disease (PD) patients. Methods: This study included a total of 361 patients with recently diagnosed de novo PD (mean age [standard deviation], 61.4 [9.8] years). The patients were classified into the following groups: APOE ɛ4 + /M (n = 65), APOE ɛ4-/M (n = 173), APOE ɛ4 + /F (n = 25), and APOE ɛ4-/F (n = 98). Cognitive decline was assessed annually over 5 years of follow-up using the Montreal Cognitive Assessment (MoCA). To assess the sex-specific impacts of the APOE ɛ4 status on cognitive decline, we used generalized linear mixed effects (GLME) models separately for men, women, and the two sexes combined. Results: In the sex-stratified GLME models adjusted for covariates, the interaction results showed that the males with APOE ɛ4 had a steeper rate of cognitive decline than those without APOE ɛ4. In contrast, there was no significant interaction between APOE ɛ4 and time on longitudinal MoCA performance in the females. The main effect of APOE ɛ4 on the change in the MoCA score was not significant for either men or women. When the data from both men and women were used, the APOE ɛ4 + /M group exhibited a steeper rate of cognitive decline than did the APOE ɛ4 + /F and APOE ɛ4-/F groups. These results were consistent with those of sensitivity analyses. Conclusion: Sex may be considered when APOE ɛ4-related vulnerability to early cognitive decline is evaluated in PD patients.

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Cholinergic Basal Forebrain Volumes Predict Gait Decline in Parkinson's Disease

Movement Disorders ◽

10.1002/mds.28453 ◽

2020 ◽

Author(s):

Joanna Wilson ◽

Alison J. Yarnall ◽

Chesney E. Craig ◽

Brook Galna ◽

Sue Lord ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Forebrain ◽

Cholinergic Basal Forebrain

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