Minor hallucinations reflect early gray matter loss and predict subjective cognitive decline in Parkinson's disease

ABSTRACT Objective: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in Parkinson’s disease (PD) are considered as the risk factors for dementia (PDD). Posterior cortically based functions, such as visuospatial and visuoperceptual (VS-VP) processing, have been described as predictors of PDD. However, no investigations have focused on the qualitative analysis of the Judgment of Line Orientation Test (JLOT) and the Facial Recognition Test (FRT) in PD-SCD and PD-MCI. The aim of this work was to study the VS-VP errors in JLOT and FRT. Moreover, these variables are considered as predictors of PDD. Method: Forty-two PD patients and 19 controls were evaluated with a neuropsychological protocol. Patients were classified as PD-SCD and PD-MCI. Analyses of errors were conducted following the procedure described by Ska, Poissant, and Joanette (1990). Follow-up assessment was conducted to a mean of 7.5 years after the baseline. Results: PD-MCI patients showed a poor performance in JLOT and FRT total score and made a greater proportion of severe intraquadrant (QO2) and interquadrant errors (IQO). PD-SCD showed a poor performance in FRT and made mild errors in JLOT. PD-MCI and QO2/IQO errors were independent risk factors for PDD during the follow-up. Moreover, the combination of both PD-MCI diagnosis and QO2/IQO errors was associated with a greater risk. Conclusions: PD-MCI patients presented a greater alteration in VS-VP processing observable by the presence of severe misjudgments. PD-SCD patients also showed mild difficulties in VS-SP functions. Finally, QO2/IQO errors in PD-MCI are a useful predictor of PDD, more than PD-MCI diagnosis alone.

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Subjective cognitive decline and progression to dementia in Parkinson’s disease: a long-term follow-up study

Journal of Neurology ◽

10.1007/s00415-019-09197-0 ◽

2019 ◽

Vol 266 (3) ◽

pp. 745-754 ◽

Cited By ~ 10

Author(s):

Iván Galtier ◽

Antonieta Nieto ◽

Jesús N. Lorenzo ◽

José Barroso

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Decline ◽

Subjective Cognitive Decline ◽

Follow Up Study ◽

Long Term Follow Up

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Side of motor onset is associated with hemisphere-specific memory decline and lateralized gray matter loss in Parkinson's disease

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2015.02.008 ◽

2015 ◽

Vol 21 (5) ◽

pp. 465-470 ◽

Cited By ~ 18

Author(s):

Eun-Young Lee ◽

Suman Sen ◽

Paul J. Eslinger ◽

Daymond Wagner ◽

Lan Kong ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gray Matter ◽

Memory Decline ◽

Specific Memory ◽

Gray Matter Loss ◽

Motor Onset

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Cognitive and cortical thinning patterns of subjective cognitive decline in patients with and without Parkinson's disease

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2014.06.011 ◽

2014 ◽

Vol 20 (9) ◽

pp. 999-1003 ◽

Cited By ~ 13

Author(s):

Jin Yong Hong ◽

Hyuk Jin Yun ◽

Mun Kyung Sunwoo ◽

Jee Hyun Ham ◽

Jong-Min Lee ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Decline ◽

Subjective Cognitive Decline ◽

Cortical Thinning

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Neural correlates and predictors of subjective cognitive decline in patients with Parkinson’s disease

Neurological Sciences ◽

10.1007/s10072-021-05734-w ◽

2021 ◽

Author(s):

Anja Ophey ◽

Fabian Krohm ◽

Elke Kalbe ◽

Andrea Greuel ◽

Alexander Drzezga ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Regression Analysis ◽

Cognitive Decline ◽

Fdg Pet ◽

Neural Correlates ◽

Motor Symptom ◽

Angular Gyrus ◽

Subjective Cognitive Decline ◽

Control Group

Abstract Background Subjective cognitive decline (SCD) may occur very early in the course of Parkinson’s disease (PD) before the onset of objective cognitive decline. Data on neural correlates and determinants of SCD in PD are rare. Objective The aim of the present study was to identify neural correlates as well as sociodemographic, clinical, and neuropsychological predictors of SCD in patients with PD. Methods We retrospectively analyzed 30 patients with PD without cognitive impairment (23% female, 66.90 ± 7.20 years, UPDRS-III: 19.83 ± 9.29), of which n = 12 patients were classified as having no SCD (control group, PD-CG) and n = 18 as having SCD (PD-SCD). Neuropsychological testing and 18-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) were conducted. SCD was assessed using a questionnaire covering multiple cognitive domains. Results SCD subscores differed significantly between PD-CG and PD-SCD and correlated significantly with other scales measuring related concepts. FDG-PET whole-brain voxel-wise regression analysis revealed hypometabolism in middle frontal, middle temporal, and occipital areas, and the angular gyrus as neural correlates of SCD in PD. Next to this hypometabolism, depressive symptoms were an independent significant determinant of SCD in a stepwise regression analysis (adjusted R2 = 50.3%). Conclusion This study strengthens the hypothesis of SCD being an early manifestation of future cognitive decline in PD and, more generally, early pathological changes in PD. The early identification of the vulnerability for future cognitive decline constitutes the basis for successful prevention and delay of this non-motor symptom.

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Cholinergic circuit genes in the healthy brain are differentially expressed in regions that exhibit gray matter loss in Parkinson’s disease

10.1101/2019.12.17.875880 ◽

2019 ◽

Author(s):

Arlin Keo ◽

Oleh Dzyubachyk ◽

Jeroen van der Grond ◽

Anne Hafkemeijer ◽

Wilma D.J. van de Berg ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gray Matter ◽

Gray Matter Volume ◽

Brain Regions ◽

Protective Role ◽

Anterior Cingulate ◽

Ras Signaling ◽

Clinical Events ◽

Gray Matter Loss

AbstractStructural covariance networks are able to identify functionally organized brain regions by gray matter volume covariance. In Parkinson’s disease, the posterior cingulate network and anterior cingulate network showed decreased gray matter and therefore we examined the underlying molecular processes of these anatomical networks in the healthy brain. Whole brain transcriptomics from post-mortem samples from healthy adults, revealed upregulation of genes associated with serotonin, GPCR, GABA, glutamate, and RAS signaling pathways in these PD-related regions. Our results also suggest involvement of the cholinergic circuit, in which genes NPPA, SOSTDC1, and TYRP1 may play a protective role. Furthermore, both networks were associated with memory and neuropsychiatric disorders that overlap with Parkinson’s disease symptoms. The identified genes and pathways contribute to healthy functions of the posterior and anterior cingulate networks and disruptions to these functions may in turn contribute to the pathological and clinical events observed in Parkinson’s disease.

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Subjective cognitive decline predicts future deterioration in cognitively normal patients with Parkinson's disease

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2013.11.017 ◽

2014 ◽

Vol 35 (7) ◽

pp. 1739-1743 ◽

Cited By ~ 21

Author(s):

Jin Yong Hong ◽

Mun Kyung Sunwoo ◽

Seok Jong Chung ◽

Jee Hyun Ham ◽

Ji E. Lee ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Decline ◽

Subjective Cognitive Decline ◽

Cognitively Normal

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Cerebrospinal fluid N-224 tau helps discriminate Alzheimer’s disease from subjective cognitive decline and other dementias

Alzheimer s Research & Therapy ◽

10.1186/s13195-020-00756-6 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Claudia Cicognola ◽

Oskar Hansson ◽

Philip Scheltens ◽

Hlin Kvartsberg ◽

Henrik Zetterberg ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Cerebrospinal Fluid ◽

Cognitive Decline ◽

Subjective Cognitive Decline ◽

Study Cohort ◽

Not Otherwise Specified ◽

T Tau

Abstract Background Elevated cerebrospinal fluid (CSF) concentrations of total tau (T-tau) and phosphorylated tau at Thr181 (P-tau181) protein are typical of Alzheimer’s disease (AD). However, the T-tau assay measures only the mid-region of the protein, while tau in CSF is instead composed of a series of fragments. One fragment species in particular, N-224, shows increased levels in AD compared to controls. In this multicentre study, we performed a clinical validation of the N-224 assay in cohorts including patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, non-AD dementias and controls. Methods Cohorts consisted of 30 SCD and 30 probable AD from the Amsterdam Dementia Cohort (cohort 1) and 539 controls, 195 SCD, 232 MCI, 137 AD and 253 non-AD from the Swedish BioFINDER study (cohort 2). All samples had AD core biomarkers (Aβ42, T-tau, P-tau181) measurements. N-224 was measured with an in-house ultrasensitive Simoa assay. Results N-224 levels were significantly higher in AD compared to SCD (cohort 1: p = 0.003) and in AD compared to all other diagnostic groups in cohort 2 (control, SCD, MCI and non-AD, p < 0.0001). Within the non-AD group, N-224 showed significantly lower concentrations compared to AD in Parkinson’s disease (PD, p < 0.0001), Parkinson’s disease dementia (PDD, p = 0.004), progressive supranuclear palsy (PSP, < 0.0001), multiple system atrophy (MSA, p = 0.002) and parkinsonisms not otherwise specified (NOS, p = 0.007). In cohort 1, higher concentrations of N-224 were associated to lower Mini-Mental State Examination (MMSE) scores (R2 = 0.318, β = 0.564, p ≤ 0.0001) and could accurately identify a pathological (< 24) MMSE score (p < 0.0001, AUC = 0.824). Conclusions N-224 tau can distinguish AD subjects from SCD and can discriminate subgroups of non-AD dementias from AD. Therefore, N-224 may be a useful addition to the tau biomarker toolbox for the study of tau species in CSF and for better understanding disease pathogenesis.

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Cingulate networks associated with gray matter loss in Parkinson’s disease show high expression of cholinergic genes in the healthy brain

European Journal of Neuroscience ◽

10.1111/ejn.15216 ◽

2021 ◽

Author(s):

Arlin Keo ◽

Oleh Dzyubachyk ◽

Jeroen van der Grond ◽

Anne Hafkemeijer ◽

Wilma D.J. van de Berg ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gray Matter ◽

High Expression ◽

Gray Matter Loss

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Cognitive function in men with non-motor features of Parkinson’s disease

BMJ Neurology Open ◽

10.1136/bmjno-2020-000112 ◽

2021 ◽

Vol 3 (1) ◽

pp. e000112

Author(s):

Mario H Flores-Torres ◽

Katherine C Hughes ◽

Samantha Molsberry ◽

Xiang Gao ◽

Jae H Kang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Cognitive Function ◽

Cognitive Decline ◽

Smoking Status ◽

Cognitive Interview ◽

Coffee Consumption ◽

Subjective Cognitive Decline ◽

Prodromal Phase

ObjectiveSubtle cognitive deficits can occur during the prodromal phase of Parkinson’s disease (PD), commonly in conjunction with hyposmia. However, little is known about the association between cognitive function and other features suggestive of prodromal PD. We evaluated the association of non-motor prodromal PD features, including hyposmia, constipation and probable REM sleep behaviour disorder (pRBD), with objective measures of cognitive function and self-reported cognitive decline.MethodsThe study population comprised 804 men who responded to a telephone cognitive interview in 2016–2017. Participants included 680 individuals with hyposmia, of whom 45 had confirmed PD, and 124 men without hyposmia. Among these men, we evaluated objective cognitive function and subjective cognitive decline to determine whether the presence of non-motor features of prodromal PD was associated with cognitive functioning. Analyses were adjusted for age, physical activity, body mass index, smoking status and coffee consumption.ResultsIndividuals with non-motor features of prodromal PD had worse objective and subjective cognitive performance relative to men without non-motor features. Cognitive impairment was particularly prevalent among individuals with concurrent hyposmia, pRBD and constipation (multivariate-adjusted OR=3.80; 95% CI 1.52 to 9.47 for objective poor cognitive function; OR=8.71; 95% CI 3.18 to 23.83 for subjective cognitive decline). As expected, both objective (OR=7.91) and subjective (OR=17.42) cognitive impairment were also more common among men with confirmed PD.ConclusionsOur study suggests that cognition is commonly affected in individuals with non-motor prodromal PD features, particularly when multiple of these features are present.

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