Development of standardized regression-based formulas to assess meaningful cognitive change in early Parkinson’s disease

Abstract Objective Longitudinal assessment of cognitive and emotional functioning in patients with Parkinson’s disease (PD) is helpful in tracking progression of the disease, developing treatment plans, evaluating outcomes, and educating patients and families. Determining whether change over time is meaningful in neurodegenerative conditions, such as PD, can be difficult as repeat assessment of neuropsychological functioning is impacted by factors outside of cognitive change. Regression-based prediction formulas are one method by which clinicians and researchers can determine whether an observed change is meaningful. The purpose of the current study was to develop and validate regression-based prediction models of cognitive and emotional test scores for participants with early-stage idiopathic PD and healthy controls (HC) enrolled in the Parkinson’s Progression Markers Initiative (PPMI). Methods Participants with de novo PD and HC were identified retrospectively from the PPMI archival database. Data from baseline testing and 12-month follow-up were utilized in this study. In total, 688 total participants were included in the present study (NPD = 508; NHC = 185). Subjects from both groups were randomly divided into development (70%) and validation (30%) subsets. Results Early-stage idiopathic PD patients and healthy controls were similar at baseline. Regression-based models were developed for all cognitive and self-report mood measures within both populations. Within the validation subset, the predicted and observed cognitive test scores did not significantly differ, except for semantic fluency. Conclusions The prediction models can serve as useful tools for researchers and clinicians to study clinically meaningful cognitive and mood change over time in PD.

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Striatal DAT and extrastriatal SERT binding in early-stage Parkinson's disease and dementia with Lewy bodies, compared with healthy controls: An 123I-FP-CIT SPECT study

NeuroImage Clinical ◽

10.1016/j.nicl.2019.101755 ◽

2019 ◽

Vol 22 ◽

pp. 101755 ◽

Cited By ~ 8

Author(s):

Merijn Joling ◽

Chris Vriend ◽

Pieter G.H.M. Raijmakers ◽

Jessica J. van der Zande ◽

Afina W. Lemstra ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dementia With Lewy Bodies ◽

Early Stage ◽

Lewy Bodies ◽

Healthy Controls

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Apathy as a behavioural marker of cognitive impairment in Parkinson’s disease: a longitudinal analysis

Journal of Neurology ◽

10.1007/s00415-019-09538-z ◽

2019 ◽

Vol 267 (1) ◽

pp. 214-227 ◽

Cited By ~ 3

Author(s):

Glen P. Martin ◽

Kathryn R. McDonald ◽

David Allsop ◽

Peter J. Diggle ◽

Iracema Leroi

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Cognitive Decline ◽

Psychiatric Symptoms ◽

Cognitive Change ◽

Longitudinal Change ◽

Random Intercept ◽

Behavioural Factors ◽

Over Time

Abstract Background Understanding the longitudinal course of non-motor symptoms, and finding markers to predict cognitive decline in Parkinson’s disease (PD), are priorities. Previous work has demonstrated that apathy is one of the only behavioural symptoms that differentiates people with PD and intact cognition from those with mild cognitive impairment (MCI-PD). Other psychiatric symptoms emerge as dementia in PD develops. Objective We explored statistical models of longitudinal change to detect apathy as a behavioural predictor of cognitive decline in PD. Methods We followed 104 people with PD intermittently over 2 years, undertaking a variety of motor, behavioural and cognitive measures. We applied a linear mixed effects model to explore behavioural factors associated with cognitive change over time. Our approach goes beyond conventional modelling based on a random-intercept and slope approach, and can be used to examine the variability in measures within individuals over time. Results Global cognitive scores worsened during the two-year follow-up, whereas the longitudinal evolution of self-rated apathy scores and other behavioural measures was negligible. Level of apathy was negatively (− 0.598) correlated with level of cognitive impairment and participants with higher than average apathy scores at baseline also had poorer cognition. The model indicated that departure from the mean apathy score at any point in time was mirrored by a corresponding departure from average global cognitive score. Conclusion High levels of apathy are predictive of negative cognitive and behavioural outcomes over time, suggesting that apathy may be a behavioural indicator of early cognitive decline. This has clinical and prognostic implications.

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Brain iron deposition is linked with cognitive severity in Parkinson’s disease

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-322042 ◽

2020 ◽

Vol 91 (4) ◽

pp. 418-425 ◽

Cited By ~ 10

Author(s):

George Edward Calver Thomas ◽

Louise Ann Leyland ◽

Anette-Eleonore Schrag ◽

Andrew John Lees ◽

Julio Acosta-Cabronero ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Brain Tissue ◽

Iron Content ◽

Rating Scale ◽

Early Stage ◽

Multiple Comparisons ◽

Cognitive Change ◽

Risk Scores ◽

Tissue Iron

BackgroundDementia is common in Parkinson’s disease (PD) but measures that track cognitive change in PD are lacking. Brain tissue iron accumulates with age and co-localises with pathological proteins linked to PD dementia such as amyloid. We used quantitative susceptibility mapping (QSM) to detect changes related to cognitive change in PD.MethodsWe assessed 100 patients with early-stage to mid-stage PD, and 37 age-matched controls using the Montreal Cognitive Assessment (MoCA), a validated clinical algorithm for risk of cognitive decline in PD, measures of visuoperceptual function and the Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 (UPDRS-III). We investigated the association between these measures and QSM, an MRI technique sensitive to brain tissue iron content.ResultsWe found QSM increases (consistent with higher brain tissue iron content) in PD compared with controls in prefrontal cortex and putamen (p<0.05 corrected for multiple comparisons). Whole brain regression analyses within the PD group identified QSM increases covarying: (1) with lower MoCA scores in the hippocampus and thalamus, (2) with poorer visual function and with higher dementia risk scores in parietal, frontal and medial occipital cortices, (3) with higher UPDRS-III scores in the putamen (all p<0.05 corrected for multiple comparisons). In contrast, atrophy, measured using voxel-based morphometry, showed no differences between groups, or in association with clinical measures.ConclusionsBrain tissue iron, measured using QSM, can track cognitive involvement in PD. This may be useful to detect signs of early cognitive change to stratify groups for clinical trials and monitor disease progression.

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Reduced habit-driven errors in Parkinson’s Disease

10.31234/osf.io/b25tf ◽

2018 ◽

Author(s):

Colin Bannard ◽

Mariana Leriche ◽

Oliver Bandmann ◽

Christopher Brown ◽

Elisa Ferracane ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Diagnosis ◽

Early Stage ◽

Healthy Controls ◽

Error Type ◽

Simple Motor ◽

Classification Of Error

Parkinson’s Disease can be understand as a disorder of motor habits. A prediction of this theory is that early stage Parkinson’s patients will display fewer errors caused by interference from previously over-learned behaviours. We test this prediction in the domain of skilled typing, where actions are easy to record and errors easy to identify. We describe a method for categorising errors as simple motor errors or habit-driven errors. We test Spanish and English participants with and without Parkinson’s, and show that indeed patients make fewer habit errors than healthy controls, and, further, that classification of error type increases the accuracy of discriminating between patients and healthy controls. As well as being a validation of a theory-led prediction, these results offer promise for automated, enhanced and early diagnosis of Parkinson’s Disease.

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Parkinson’s Disease Motor Subtypes Change with the Progression of the Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up

Journal of Parkinson s Disease ◽

10.3233/jpd-213004 ◽

2021 ◽

pp. 1-21

Author(s):

Diego Santos García ◽

Hector Canfield ◽

Teresa de Deus Fonticoba ◽

Carlos Cores Bartolomé ◽

Lucía Naya Ríos ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Daily Living ◽

Cognitive Status ◽

Postural Instability ◽

Change Over Time ◽

Factors Associated ◽

Baseline Visit ◽

Over Time

Background: Motor phenotype (MP) can be associated with a different prognosis in Parkinson’s disease (PD), but it is not fixed and can change over time. Objective: Our aim was to analyze how the MP changed over time and to identify factors associated with the changes in PD patients from a multicenter Spanish PD cohort. Methods: PD patients who were recruited from January-2016 to November-2017 (baseline visit; V0) and evaluated again at a 2-year±30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this study.MP was calculated at both visits based on Jankovic classification in TD (tremor dominant), IND (indeterminate), or PIGD (postural instability and gait difficulty). Sociodemographic and clinical data were collected, including serum biomarkers. Results: Five hundred eleven patients (62.57±8.59 years old; 59.2%males) were included in the study. At V0, MP was: 47.4%(242/511) TD; 36.6%(187/511) PIGD; 16%(82/511) IND. Up to 38%(194/511) of the patients changed their phenotype from V0 to V2, being the most frequent from TD to IND (8.4%) and from TD to PIGD (6.7%). A worse cognitive status (OR = 0.966) and less autonomy for activities of daily living (OR = 0.937) at V0 and a greater increase in the globalNMS burden (OR = 1.011) from V0 to V2 were associated with changing from TD to another phenotype after 2-year follow-up. Conclusion: The MP in PD can change over time. With disease progression, the percentage of cases with non-tremoric MP increases. PD patients who changed from TD to postural instability and gait difficulty increased NMS burden significantly.

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Diagnostic accuracy of glabellar tap sign for Parkinson’s disease

Journal of Neural Transmission ◽

10.1007/s00702-021-02391-3 ◽

2021 ◽

Author(s):

Simo Nuuttila ◽

Mikael Eklund ◽

Juho Joutsa ◽

Elina Jaakkola ◽

Elina Mäkinen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Diagnostic Value ◽

Clinical Test ◽

Diagnostic Validity ◽

Healthy Controls ◽

Validity And Reliability ◽

Dopaminergic Activity ◽

Over Time

AbstractGlabellar tap or reflex (GR) is an old bedside clinical test used in the diagnostics of Parkinson’s disease (PD), but its diagnostic value is unclear. This study examines the diagnostic validity and reliability of GR in PD in relation to brain dopaminergic activity. GR was performed on 161 patients with PD, 47 patients with essential tremor (ET) and 40 healthy controls immediately prior to dopamine transporter (DAT) [123I]FP-CIT SPECT scanning. The binding ratios were investigated with consideration of the GR result (normal/abnormal). In addition, the consistency of the GR was investigated with 89 patients after a mean follow-up of 2.2 years. PD and ET patients had higher GR scores than healthy controls (p < 0.001), but there was no difference in GR between PD and ET patients (p = 0.09). There were no differences in the ratio of abnormal to normal GRs between the PD and ET groups (73% vs. 64% abnormal, respectively, p = 0.13) or in DAT binding between PD patients with abnormal and normal GRs (p > 0.36). Over follow-up, the GR changed from abnormal to normal in 20% of PD patients despite the presence of clinically typical disease. The sensitivity and specificity of GR for differentiating PD from ET were 78.3% and 36.2%, respectively. Although GR has been used by clinicians in the diagnostics of PD, it does not separate PD from ET. It also shows considerable inconsistency over time, and abnormal GR has no relationship with dopamine loss. Its usefulness should be tested for other clinical diagnostic purposes.

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Circulating CircRNAs Panel Acts as a Biomarker for the Early Diagnosis and Severity of Parkinson’s Disease

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.684289 ◽

2021 ◽

Vol 13 ◽

Author(s):

Lingling Zhong ◽

KeJu Ju ◽

Ainian Chen ◽

Hua Cao

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Diagnosis ◽

Disease Progression ◽

Clinical Symptoms ◽

Early Stage ◽

Healthy Controls ◽

Training Set ◽

The Central Nervous System

Parkinson’s disease (PD) is a chronic and progressive degenerative disease of the central nervous system. Degenerative neuropathy can occur in patients with PD even before typical clinical symptoms appear in the preclinical stage. Therefore, if the early diagnosis of degenerative diseases can be timely and the correlation with the disease progression can be explored, the disease progression will be slowed down and the quality of life of patients will be improved. In this study, the circRNA microarray was employed to screen the dysregulated circRNA in plasma samples of PD. Four circRNAs (circ_0085869, circ_0004381, circ_0017204, and circ_0090668) were obtained with increased levels in PD patients by cross comparison and preliminary verification in PD comparing with healthy controls. Further validation found the circRNA panel was consistent with the training set. The ROC curve also revealed a high diagnostic ability of circ_0004381 and circ_0017204 in predicting the early stage of PD from healthy controls. circ_0085869, circ_0004381, circ_0017204, and circ_0090668 also presented a high ability to distinguish the late stage of PD from early stage. In conclusion, circulating circRNA panel might be a potential fingerprint for predicting the early diagnosis of PD and may act as a biomarker for disease progression.

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Pre- and Postsynaptic Dopamine SPECT in Idiopathic Parkinsonian Diseases: A Follow-Up Study

BioMed Research International ◽

10.1155/2013/143532 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 7

Author(s):

Susanna Jakobson Mo ◽

Jan Linder ◽

Lars Forsgren ◽

Henrik Holmberg ◽

Anne Larsson ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Multiple System Atrophy ◽

Progressive Supranuclear Palsy ◽

Healthy Controls ◽

Follow Up Study ◽

The Mean ◽

One Year ◽

Over Time

We prospectively evaluated the diagnostic contribution of123I-FP-Cit (DAT) and123I-IBZM (IBZM) SPECT in 29 patients with Parkinson's disease (PD) (74.4±4.2years) and 28 patients with atypical parkinsonian diseases (APD) (74.3±9.2years). Twelve had multiple system atrophy (MSA) and 16 progressive supranuclear palsy (PSP). Sixteen age-matched healthy controls (HC) were included. DAT and IBZM SPECTs were made at baseline and after 1 year in all PD patients and in 20 (DAT) and 18 (IBZM) of the APD patients, and after 3 years in 22 (DAT) and 17 (IBZM) of the PD patients and in 10 (DAT) and 10 (IBZM) of the APD patients. The relative DAT uptake decrease was faster in PD and PSP than in HC and MSA. In PSP the DAT uptake was lower than in MSA after 1 year but not after 3 years. Baseline IBZM uptake was not significantly different between patients and HC or between PD and APD. One year after initiated dopaminergic treatment the mean IBZM uptake in the MSA patients remained high compared to PSP and after 3 years compared to PD, PSP, and HC. Thus, the pattern of uptake of these ligands over time may be of value in discriminating between these diagnoses.

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Cognitive Change in Newly-Diagnosed Patients with Parkinson's Disease: A 5-Year Follow-up Study

Journal of the International Neuropsychological Society ◽

10.1017/s1355617713000295 ◽

2013 ◽

Vol 19 (6) ◽

pp. 695-708 ◽

Cited By ~ 48

Author(s):

Mark Broeders ◽

Daan C. Velseboer ◽

Rob de Bie ◽

Johannes D. Speelman ◽

Dino Muslimovic ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Decline ◽

Age At Onset ◽

Cognitive Change ◽

Healthy Controls ◽

Newly Diagnosed ◽

Cognitive Changes ◽

Cognitive Domains ◽

Healthy Elderly

AbstractCognitive change is frequently observed in patients with Parkinson's disease (PD). However, the exact profile and extent of cognitive impairments remain unclear due to the clinical heterogeneity of PD and methodological issues in many previous studies. In this study, we aimed to examine the severity, frequency, and profile of cognitive changes in newly diagnosed PD patients over 5 years. At baseline and after 3 and 5 years, a hospital-based sample of PD patients (n = 59) and healthy controls (n = 40) were given neuropsychological tests covering six cognitive domains. Patients showed greater decline over time than healthy controls on all cognitive domains, except for attention. The profile of decline showed that psychomotor speed and memory were most affected. At the individual level 53% of the patients showed more cognitive decline than controls. Age at onset and memory impairment at baseline predicted cognitive decline. Cognitive functions in PD patients show greater decline in most domains than in healthy elderly over the course of 5 years. Due to selection bias as a result of attrition, the actual degree of decline may be greater than reported here. (JINS, 2013, 19, 1–14)

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