Cerebrospinal Fluid, Imaging, and Physiological Biomarkers in Dementia With Lewy Bodies

Dementia with Lewy bodies is a progressive neurodegenerative disorder, clinically characterized by gradual cognitive impairment and fluctuating cognition, behavioral changes and recurrent visual hallucinations, and autonomic function and movement symptoms in the type of parkinsonism. It is the second most common type of dementia in the Western world after Alzheimer disease. Over the last 20 years, many neurophysiological, neuroimaging, and cerebrospinal fluid (CSF) biomarkers have been described toward a better discrimination between dementia with Lewy bodies, Alzheimer disease, and other neurodegenerative conditions.In the present review, we aim to describe the neurophysiological, imaging, and CSF biomarkers in dementia with Lewy bodies and to question whether they could be reliable tools for the clinical practice.

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Cerebrospinal Fluid Hypocretin and Nightmares in Dementia Syndromes

Dementia and Geriatric Cognitive Disorders Extra ◽

10.1159/000509585 ◽

2021 ◽

pp. 19-25

Author(s):

Lynn Marie Trotti ◽

Donald L. Bliwise ◽

Glenda L. Keating ◽

David B. Rye ◽

William T. Hu

Keyword(s):

Cerebrospinal Fluid ◽

Alzheimer Disease ◽

Cholinesterase Inhibitor ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Cognitively Normal ◽

Dementia Patients ◽

Sleep Questionnaires ◽

Sleep Alterations ◽

Normal Controls

Background/Aims: Hypocretin promotes wakefulness and modulates REM sleep. Alterations in the hypocretin system are increasingly implicated in dementia. We evaluated relationships among hypocretin, dementia biomarkers, and sleep symptoms in elderly participants, most of whom had dementia. Methods: One-hundred twenty-six adults (mean age 66.2 ± 8.4 years) were recruited from the Emory Cognitive Clinic. Diagnoses were Alzheimer disease (AD; n = 60), frontotemporal dementia (FTD; n = 21), and dementia with Lewy bodies (DLB; n = 20). We also included cognitively normal controls (n = 25). Participants and/or caregivers completed sleep questionnaires and lumbar puncture was performed for cerebrospinal fluid (CSF) assessments. Results: Except for sleepiness (worst in DLB) and nocturia (worse in DLB and FTD) sleep symptoms did not differ by diagnosis. CSF hypocretin concentrations were available for 87 participants and normal in 70, intermediate in 16, and low in 1. Hypocretin levels did not differ by diagnosis. Hypocretin levels correlated with CSF total τ levels only in men (r = 0.34; p = 0.02). Lower hypocretin levels were related to frequency of nightmares (203.9 ± 29.8 pg/mL in those with frequent nightmares vs. 240.4 ± 46.1 pg/mL in those without; p = 0.05) and vivid dreams (209.1 ± 28.3 vs. 239.5 ± 47.8 pg/mL; p = 0.014). Cholinesterase inhibitor use was not associated with nightmares or vivid dreaming. Conclusion: Hypocretin levels did not distinguish between dementia syndromes. Disturbing dreams in dementia patients may be related to lower hypocretin concentrations in CSF.

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VGF Peptides in Cerebrospinal Fluid of Patients with Dementia with Lewy Bodies

International Journal of Molecular Sciences ◽

10.3390/ijms20194674 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4674 ◽

Cited By ~ 3

Author(s):

Inger van Steenoven ◽

Barbara Noli ◽

Cristina Cocco ◽

Gian-Luca Ferri ◽

Patrick Oeckl ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Cognitive Decline ◽

Analytical Methods ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Disease Stage ◽

Selected Reaction Monitoring ◽

Csf Biomarkers ◽

Potential Biomarker ◽

Proteomic Study

In a previous proteomic study, we identified the neurosecretory protein VGF (VGF) as a potential biomarker for dementia with Lewy bodies (DLB). Here, we extended the study of VGF by comparing levels in cerebrospinal fluid (CSF) from 44 DLB patients, 20 Alzheimer’s disease (AD) patients, and 22 cognitively normal controls selected from the Amsterdam Dementia Cohort. CSF was analyzed using two orthogonal analytical methods: (1) In-house-developed quantitative ELISA and (2) selected reaction monitoring (SRM). We further addressed associations of VGF with other CSF biomarkers and cognition. VGF levels were lower in CSF from patients with DLB compared to either AD patients or controls. VGF was positively correlated with CSF tau and α-synuclein (0.55 < r < 0.75), but not with Aβ1-42. In DLB patients, low VGF levels were related to a more advanced cognitive decline at time of first presentation, whereas high levels of VGF were associated with steeper subsequent longitudinal cognitive decline. Hence, CSF VGF levels were lower in DLB compared to both AD and controls across different analytical methods. The strong associations with cognitive decline further points out VGF as a possible disease stage or prognostic marker for DLB.

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Cerebrospinal Fluid Biomarkers for Dementia with Lewy Bodies

International Journal of Alzheimer s Disease ◽

10.4061/2010/536538 ◽

2010 ◽

Vol 2010 ◽

pp. 1-17 ◽

Cited By ~ 7

Author(s):

Elizabeta B. Mukaetova-Ladinska ◽

Rachael Monteith ◽

Elaine K. Perry

Keyword(s):

Cerebrospinal Fluid ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Low Frequency ◽

Csf Biomarkers ◽

Term Care ◽

Clinical Criteria ◽

Cerebrospinal Fluid Biomarkers ◽

The Uk ◽

T Tau

More than 750,000 of the UK population suffer from some form of cognitive impairment and dementia. Of these, 5–20% will have Dementia with Lewy Bodies (DLB). Clinico-pathological studies have shown that it is the low frequency of DLB clinical core features that makes the DLB diagnosis hardly recognisable during life, and easily misdiagnosed for other forms of dementia. This has an impact on the treatment and long-term care of the affected subjects. Having a biochemical test, based on quantification of a specific DLB biomarker within Cerebrospinal Fluid (CSF) could be an effective diagnostic method to improve the differential diagnosis. Although some of the investigated DLB CSF biomarkers are well within the clinical criteria for sensitivity and specificity (90%), they all seem to be confounded by the contradictory data for each of the major groups of biomarkers (-synuclein, tau and amyloid proteins). However, a combination of CSF measures appear to emerge, that may well be able to differentiate DLB from other dementias: -synuclein reduction in early DLB, a correlation between CSF -synuclein and A42 measures (characteristic for DLB only), and t-tau and p-tau181 profile (differentiating AD from DLB).

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P2-070: Imaging and cerebrospinal fluid (CSF) biomarkers for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD): A meta-analysis of test performance

Alzheimer s & Dementia ◽

10.1016/j.jalz.2013.05.713 ◽

2013 ◽

Vol 9 ◽

pp. P368-P369

Author(s):

Takashi Nihashi ◽

Teruhiko Terasawa ◽

Aki Mishima ◽

Yoshio Ando ◽

Hisashi Kawai ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Test Performance ◽

Dementia With Lewy Bodies ◽

Meta Analysis ◽

Lewy Bodies ◽

Csf Biomarkers

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Utility of Autonomic Function Tests to Differentiate Dementia with Lewy Bodies and Parkinson Disease with Dementia from Alzheimer Disease

European Neurology ◽

10.1159/000484409 ◽

2017 ◽

Vol 79 (1-2) ◽

pp. 27-32 ◽

Cited By ~ 5

Author(s):

Shuta Toru ◽

Tadashi Kanouchi ◽

Takanori Yokota ◽

Yosuke Yagi ◽

Akira Machida ◽

...

Keyword(s):

Alzheimer Disease ◽

Parkinson Disease ◽

Dementia With Lewy Bodies ◽

Autonomic Function ◽

Lewy Bodies ◽

Sympathetic Skin Response ◽

Tilt Test ◽

Autonomic Function Tests ◽

Function Tests ◽

Skin Response

Objective: We studied autonomic disturbance in patients with dementia with Lewy bodies (DLB), Parkinson disease with dementia (PDD), Alzheimer disease (AD), to determine whether autonomic function tests can be used to distinguish these disorders. Methods: Autonomic function was tested in 56 patients with DLB, 37 patients with PDD, and 59 patients with AD by using the sympathetic skin response, coefficient of variation in R-R interval, the head-up tilt test, serum norepinephrine concentration, and 123I-meta-iodobenzylguanidine cardiac scintigraphy. Symptoms of autonomic dysfunction, such as constipation, urinary symptoms, and orthostatic hypotension, were also noted. Results: The groups did not differ on baseline characteristics other than those associated with Parkinsonism and dementia. All patients with DLB and PDD had some dysautonomia, whereas rates were much lower for patients with AD (19%). Significantly more DLB and PDD patients than AD patients showed abnormalities on autonomic function tests. Conclusions: Autonomic function tests might be quite useful to distinguish DLB and PDD from AD.

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