Sex-specific associations with cerebrospinal fluid biomarkers in dementia with Lewy bodies

Beek, Marleen van de; Mofrad, Rosha Babapour; Steenoven, Inger van; Vanderstichele, Hugo; Scheltens, Philip; Teunissen, Charlotte E.; Lemstra, Afina W.; Flier, Wiesje M. van der

doi:10.1186/s13195-020-00610-9

Cited by 28 publications

(42 citation statements)

References 44 publications

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“…Yet, percentage of male subjects was kept similar across groups. Although sex differences can have a relevant impact on biomarker levels in DLB [ 43 ], they were not included as a parameter in our models, due to the limited power for most study groups. All statistics were performed using IBM ® SPSS statistics version 26 (Armonk, NY, USA).…”

Section: Methodsmentioning

confidence: 99%

Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF

Boiten

Steenoven

Xiao

et al. 2020

Cells

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Background: Dementia with Lewy bodies (DLB) is a neurodegenerative disease where synaptic loss and reduced synaptic integrity are important neuropathological substrates. Neuronal Pentraxin 2(NPTX2) is a synaptic protein that drives the GABAergic inhibitory circuit. Our aim was to examine if NPTX2 cerebral spinal fluid (CSF) levels in DLB patients were altered and how these levels related to other synaptic protein levels and to cognitive function and decline. Methods: NPTX2, VGF, and α-synuclein levels were determined in CSF of cognitive healthy (n = 27), DLB (n = 48), and AD (n = 20) subjects. Multiple cognitive domains were tested, and data were compared using linear models. Results: Decreased NPTX2 levels were observed in DLB (median = 474) and AD (median = 453) compared to cognitive healthy subjects (median = 773). Strong correlations between NPTX2, VGF, and α-synuclein were observed dependent on diagnosis. Combined, these markers had a high differentiating power between DLB and cognitive healthy subjects (AUC = 0.944). Clinically, NPTX2 levels related to global cognitive function and cognitive decline in the visual spatial domain. Conclusion: NPTX2 CSF levels were reduced in DLB and closely correlated to decreased VGF and α-synuclein CSF levels. CSF NPTX2 levels in DLB related to decreased functioning in the visual spatial domain.

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Section: Methodsmentioning

confidence: 99%

Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF

Boiten

Steenoven

Xiao

et al. 2020

Cells

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“…We have no clear explanation for this. In a previous study, we found that DLB manifests differently in women than in men, with more severe cognitive impairment and more frequent AD co-pathology in women [77]. It is imaginable that DLB in women is more often not recognized.…”

Section: Limitationsmentioning

confidence: 89%

Characterization of symptoms and determinants of disease burden in dementia with Lewy bodies: DEvELOP design and baseline results

et al. 2021

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Background The DEmEntia with LEwy bOdies Project (DEvELOP) aims to phenotype patients with dementia with Lewy bodies (DLB) and study the symptoms and biomarkers over time. Here, we describe the design and baseline results of DEvELOP. We investigated the associations between core and suggestive DLB symptoms and different aspects of disease burden, i.e., instrumental activities of daily living (IADL) functioning, quality of life (QoL), and caregiver burden. Methods We included 100 DLB patients (69 ± 6 years, 10%F, MMSE 25 ± 3) in the prospective DEvELOP cohort. Patients underwent extensive assessment including MRI, EEG/MEG, 123FP-CIT SPECT, and CSF and blood collection, with annual follow-up. Core (hallucinations, parkinsonism, fluctuations, RBD) and suggestive (autonomous dysfunction, neuropsychiatric symptoms) symptoms were assessed using standardized questionnaires. We used multivariate regression analyses, adjusted for age, sex, and MMSE, to evaluate how symptoms related to the Functional Activities Questionnaire, QoL-AD questionnaire, and Zarit Caregiver Burden Interview. Results In our cohort, RBD was the most frequently reported core feature (75%), while visual hallucinations were least frequently reported (39%) and caused minimal distress. Suggestive clinical features were commonly present, of which orthostatic hypotension was most frequently reported (64%). Ninety-five percent of patients showed EEG/MEG abnormalities, 88% of 123FP-CIT SPECT scans were abnormal, and 53% had a CSF Alzheimer’s disease profile. Presence of fluctuations, lower MMSE, parkinsonism, and apathy were associated with higher IADL dependency. Depression, constipation, and lower IADL were associated with lower QoL-AD. Apathy and higher IADL dependency predisposed for higher caregiver burden. Conclusion Baseline data of our prospective DLB cohort show clinically relevant associations between symptomatology and disease burden. Cognitive and motor symptoms are related to IADL functioning, while negative neuropsychiatric symptoms and functional dependency are important determinants of QoL and caregiver burden. Follow-up is currently ongoing to address specific gaps in DLB research.

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“…This large-scale study agrees with the balanced sex distribution in DLB compared with AD and PD-PDD. Regarding biomarkers in the CSF of patients with DLB, women had lower alpha-synuclein (α-syn) CSF Aβ42 levels compared to men, and no sex differences for phospho-tau concentrations were found [50].…”

Section: Dementia With Lewy Bodies (Dlb)mentioning

confidence: 99%

From Menopause to Neurodegeneration—Molecular Basis and Potential Therapy

Cheng

Lin

Lane

2021

IJMS

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The impacts of menopause on neurodegenerative diseases, especially the changes in steroid hormones, have been well described in cell models, animal models, and humans. However, the therapeutic effects of hormone replacement therapy on postmenopausal women with neurodegenerative diseases remain controversial. The steroid hormones, steroid hormone receptors, and downstream signal pathways in the brain change with aging and contribute to disease progression. Estrogen and progesterone are two steroid hormones which decline in circulation and the brain during menopause. Insulin-like growth factor 1 (IGF-1), which plays an import role in neuroprotection, is rapidly decreased in serum after menopause. Here, we summarize the actions of estrogen, progesterone, and IGF-1 and their signaling pathways in the brain. Since the incidence of Alzheimer’s disease (AD) is higher in women than in men, the associations of steroid hormone changes and AD are emphasized. The signaling pathways and cellular mechanisms for how steroid hormones and IGF-1 provide neuroprotection are also addressed. Finally, the molecular mechanisms of potential estrogen modulation on N-methyl-d-aspartic acid receptors (NMDARs) are also addressed. We provide the viewpoint of why hormone therapy has inconclusive results based on signaling pathways considering their complex response to aging and hormone treatments. Nonetheless, while diagnosable AD may not be treatable by hormone therapy, its preceding stage of mild cognitive impairment may very well be treatable by hormone therapy.

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Sex-specific associations with cerebrospinal fluid biomarkers in dementia with Lewy bodies

Cited by 28 publications

References 44 publications

Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF

Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF

Characterization of symptoms and determinants of disease burden in dementia with Lewy bodies: DEvELOP design and baseline results

From Menopause to Neurodegeneration—Molecular Basis and Potential Therapy

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