Inger van Steenoven

Conversion Between Mini-Mental State Examination, Montreal Cognitive Assessment, and Dementia Rating Scale-2 Scores in Parkinson’s Disease

Cognitive impairment is one of the earliest, most common, and most disabling non‐motor symptoms in Parkinsons disease (PD). Thus, routine screening of global cognitive abilities is important for the optimal management of PD patients. Few global cognitive screening instruments have been developed for or validated in PD patients. The Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Dementia Rating Scale‐2 (DRS‐2) have been used extensively for cognitive screening in both clinical and research settings. Determining how to convert the scores between instruments would facilitate the longitudinal assessment of cognition in clinical settings and the comparison and synthesis of cognitive data in multicenter and longitudinal cohort studies. The primary aim of this study was to apply a simple and reliable algorithm for the conversion of MoCA to MMSE scores in PD patients. A secondary aim was to apply this algorithm for the conversion of DRS‐2 to both MMSE and MoCA scores. The cognitive performance of a convenience sample of 360 patients with idiopathic PD was assessed by at least two of these cognitive screening instruments. We then developed conversion scores between the MMSE, MoCA, and DRS‐2 using equipercentile equating and log‐linear smoothing. The conversion score tables reported here enable direct and easy comparison of three routinely used cognitive screening assessments in PD patients.

Alzheimer's disease cerebrospinal fluid biomarkers predict cognitive decline in lewy body dementia

Alzheimers disease pathologies are common in dementia with Lewy bodies, but their clinical relevance is not clear. CSF biomarkers amyloid beta 1‐42, total tau, and tau phosphorylated at threonine 181 reflect Alzheimers disease neuropathology antemortem. In PD, low CSF amyloid beta 1‐42 predict long‐term cognitive decline, but little is known about these biomarkers as predictors for cognitive decline in Lewy body dementia. The aim of this study was to assess whether Alzheimers disease CSF biomarkers predict cognitive decline in Lewy body dementia.

Cerebrospinal fluid Alzheimer's disease biomarkers across the spectrum of lewy body diseases: Results from a large multicenter cohort

BACKGROUND Concomitant Alzheimers disease (AD) pathology is observed in Lewy body diseases (LBD), but the clinical impact is unknown. Only a few biomarker studies in LBD exist and have included small cohorts from single centers. OBJECTIVE We aimed to evaluate the prevalence of abnormal cerebrospinal fluid (CSF) AD biomarkers across the spectrum of LBD in a large multicenter cohort and to assess whether an AD biomarker profile was associated with demographic and clinical differences in dementia with Lewy bodies (DLB). METHODS We included 375 DLB patients, 164 Parkinsons disease (PD) patients without dementia, and 55 PD patients with dementia (PDD) from 10 centers. CSF amyloid-beta42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) values were dichotomized as abnormal or normal according to locally available cut-off values. A CSF AD profile was defined as abnormal Aβ42 combined with abnormal t-tau and/or p-tau. RESULTS A substantial proportion of DLB patients had abnormal values for CSF Aβ42, t-tau, and p-tau, while abnormal values were uncommon in PD without dementia. Patients with PDD had values in between. A CSF AD profile was observed in 25% of DLB patients, compared with only 9% of PDD and 3% of PD without dementia. Within DLB, patients with a CSF AD profile were older, more often female, performed worse on the Mini-Mental State Examination, and had shorter disease duration compared with patients with normal CSF. CONCLUSION A CSF AD profile is more common in DLB compared with PDD and PD, and is associated with more severe cognitive impairment in DLB.

An update on the genetics of dementia with Lewy bodies

The genetic architecture of dementia with Lewy bodies (DLB) is increasingly taking shape. Initially, genetic research focused mainly on linkage and candidate gene studies in small series of DLB patients. More recently, association and exome sequencing studies in larger groups have been conducted, and have shown that several variants in GBA and the APOE ε4 allele are important genetic risk factors for DLB. However, genetic research in DLB is still in its infancy. So far, many genetic studies have been biased and performed in clinically and pathologically heterogeneous populations. Therefore, it is likely that multiple DLB-specific genetic determinants still have to be identified. To further our understanding of the role of genetics in DLB, future genetic studies should be unbiased and performed in large series of DLB patients, ideally with both a clinical diagnosis and pathological confirmation. The combination of genomic techniques with other research modalities, such as proteomic research, is a promising approach to identify novel genetic determinants. More knowledge about the genetics of DLB will increase our understanding of the pathophysiology of the disease and its relation with Parkinsons Disease and Alzheimers Disease, and may eventually lead to the development of disease modifying treatments.

EEG Characteristics of Dementia With Lewy Bodies, Alzheimer’s Disease and Mixed Pathology

Introduction: Previous studies on electroencephalography (EEG) to discriminate between dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) have been promising. These studies did not consider the pathological overlap of the two diseases. DLB-patients with concomitant AD pathology (DLB/AD+) have a more severe disease manifestation. The EEG may also be influenced by a synergistic effect of the two pathologies. We aimed to compare EEG characteristics between DLB/AD+, “pure” DLB (DLB/AD−) and AD. Methods: We selected probable DLB patients who had an EEG and cerebrospinal fluid (CSF) available, from the Amsterdam Dementia Cohort (ADC). Concomitant AD-pathology was defined as a CSF tau/Aβ-42 ratio > 0.52. Forty-one DLB/AD+ cases were matched for age (mean 70 (range 53–85)) and sex (85% male) 1:1 to DLB/AD− and AD-patients. EEGs were assessed visually, with Fast Fourier Transform (FFT), network- and connectivity measures. Results: EEG visual severity score (range 1–5) did not differ between DLB/AD− and DLB/AD+ (2.7 in both groups) and was higher compared to AD (1.9, p < 0.01). Both DLB groups had a lower peak frequency (7.0 Hz and 6.9 Hz in DLB vs. 8.2 in AD, p < 0.05), more slow-wave activity and more prominent disruptions of connectivity and networks, compared to AD. No significant differences were found between DLB/AD+ and DLB/AD−. Discussion: EEG abnormalities are more pronounced in DLB, regardless of AD co-pathology. This emphasizes the valuable role of EEG in discriminating between DLB and AD. It suggests that EEG slowing in DLB is influenced more by the α-synucleinopathy, or the associated cholinergic deficit, than by amyloid and tau pathology.

CSF AMYLOID-β PEPTIDES IN DEMENTIA WITH LEWY BODIES AND ALZHEIMER’S DISEASE

Sample 297 82 215 Age 75.15 75.57 75.00 0.89 Mean (s.d.) (6.95) (6.78) (7.02) % Male 61.28 64.63 60 0.46 % ApoE 49.8% 9.75 65.12 < 0.001 Clinical Diagnostic Category (HC:MCI: AD) 83 : 145 : 69 49 : 29 : 4 34 : 116 : 65 <0.001 Education (years) Mean (s.d.) 15.63 (2.95) 15.68 (2.87) 15.61 (2.99) 0.94 CSF Ab1-42 (pg/mL) Mean (s.d.) 167.65 (53.10) 244.60 (25.17) 138.30 (22.94) <0.001 CSF t-tau (pg/mL) Mean (s.d.) 98.80 (54.52) 58.21 (15.51) 114.28 (56.11) <0.001 CSF P-tau (pg/mL) Mean (s.d.) 35.52 (22.10) 20.14 (7.94) 41.43 (22.94) <0.001 Abbreviations: pg/mL1⁄4 picograms per milliliter, s.d.1⁄4 StandardDeviation,%APOE1⁄4 proportion of APOE ε4 carriers, HC1⁄4Healthy Controls,MCI1⁄4Mild Cognitive Impairment, AD 1⁄4 Alzheimer’s disease dementia.

IDENTIFICATION OF NOVEL CEREBROSPINAL FLUID BIOMARKER CANDIDATES FOR DEMENTIA WITH LEWY BODIES: A PROTEOMIC APPROACH

Paired phosphorylated and unphosphorylated peptides at sites T181, S202, T205 and T217 were quantified. Relationships between tau phosphorylation and [F]GTP1 SUVRwere assessed using Spearman correlation analysis. The false discovery rate (FDR) for ROI-level correlation analyses was controlled using the Benjamini-Hochberg procedure. Results: [F]GTP1 SUVR and CSF tau phosphorylation increase with disease severity (expressed as the ratio of phosphorylated to unphosphorylated peptides). Spearman correlation analysis reveals that in n1⁄438 individuals T217 (r1⁄40.69) and T205 (r1⁄40.55) are more correlated with [F]GTP1 (whole-cortical gray) SUVR than T181 (r1⁄40.28). Correlations strengthen when using a more specific AD-meta ROI (Jack et al., 2017) to calculate [F]GTP1 SUVR, with T217 having the strongest correlation (r1⁄40.81) (T205, r1⁄40.63, T181 r1⁄40.35). Preliminary comparisons of different regional analyses of [F]GTP1, and relationships with cognitive endpoints may also be presented. Conclusions:These results provide insight into the relationship between tau PET imaging and CSF phospho-tau, and may help guide the usage and interpretation of biomarker data in the clinic. CSF species containing phosphosites T217 and T205 may be more closely reflective of tauopathy, as detected by tau PET.

ELECTRO-ENCEPHALOGRAPHY AS A PRODROMAL MARKER OF DEMENTIA WITH LEWY BODIES

Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino-First, Genoa, Italy; Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom; Department of Neuroscience, Mental Health and Sensory Organs, University of Rome La Sapienza, Rome, Italy; Department of Neuroscience Imaging and Clinical Sciences, Centro di Scienze dell’Invecchiamento, University G d’Annunzio of Chieti-Pescara, Chieti, Italy; Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Rome, Italy; Universit€atsspital Basel, Basel, Switzerland; Johannes Kepler University Linz, Linz, Austria; Austrian Institute of Technology GmbH, Wien, Austria; Lab Alzheimer’s Neuroimaging and Epidemiology, Istituto di Ricovero e Cura a Carattere Scientifico Fatebenefratelli, Brescia, Italy; Department of Neurology and Psychiatry, Sapienza, University of Rome, Rome, Italy; Istanbul Medipol University, Istanbul, Turkey; Department of Neurology, University of Istanbul-Medipol, Istanbul, Turkey; Dokuz Eyl€ul University, Izmir, Turkey; Dokuz Eyl€ul University, Izmir, Turkey; Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy; University G. d’Annunzio of Chieti-Pescara, Chieti, Italy; Newcastle University, Institute of Neuroscience, Newcastle upon Tyne, United Kingdom; Casa di Cura Privata del Policlinico, Milano SpA, Milan, Italy; Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Rome, Italy; Hospital San Raffaele of Cassino, Cassino, Italy; Universit a degli Studi G. d’Annunzio Chieti e Pescara, Chieti, Italy. Contact e-mail: claudio.babiloni@uniroma1.it

ALPHA-SYNUCLEIN SPECIES AS POTENTIAL CSF BIOMARKERS FOR DEMENTIA WITH LEWY BODIES

Background: The discovery of alpha-synuclein (a-syn) as a major component of Lewy bodies lead to the idea that a-syn could be a potential cerebrospinal fluid (CSF) biomarker for dementia with Lewy bodies (DLB). So far, studies measuring CSF total a-syn have yielded conflicting results. However, recent studies showed that a combination of CSF a-syn species may improve the diagnostic value of a-syn in synucleinopathies. In this study we assessed the diagnostic value of different CSF a-syn species (total-, oligomericand pS129-a-syn) for DLB. Methods:We measured the levels of CSF a-syn species in DLB (n=42), Alzheimers disease (AD) (n=39), Parkinsons disease (PD) (n=46), subjective cognitive decline (SCD) (n=31) and healthy controls (HC) (n=48) using newly developed ELISAs (Majbour et al., 2016). Linear regression analysis corrected for age and gender were performed to assess differences in a-syn levels between diagnostic groups. In addition, we used receiver operation characteristic (ROC) analysis and logistic regression analysis to determine the diagnostic accuracy between DLB and AD and between DLB and controls (SCD + HC) of (the combination of) the a-syn biomarker(s). Results: The levels of total- a-syn in CSF were decreased in DLB (1.48+/-0.08ng/ml) and PD (1.41+/-0.05ng/ml) compared to AD (2.14+/-0.14ng/ml, p