Cerebrospinal Fluid Hypocretin and Nightmares in Dementia Syndromes

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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Amyloid-β peptides in cerebrospinal fluid of patients with dementia with Lewy bodies

Alzheimer s Research & Therapy ◽

10.1186/s13195-019-0537-5 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Inger van Steenoven ◽

Wiesje M. van der Flier ◽

Philip Scheltens ◽

Charlotte E. Teunissen ◽

Afina W. Lemstra

Keyword(s):

Cerebrospinal Fluid ◽

Dementia With Lewy Bodies ◽

Mmse Score ◽

Apoe Genotype ◽

Lewy Bodies ◽

Amyloid Β ◽

Aβ Peptide ◽

Aβ Peptides ◽

Cognitively Normal ◽

Normal Controls

Abstract Background One of the major challenges in diagnosing dementia with Lewy bodies (DLB) is the common co-morbid presence of amyloid pathology. To understand the putative role of altered amyloid-β (Aβ) metabolism in dementia with DLB, we analyzed levels of different cerebrospinal fluid (CSF) Aβ peptides (Aβ38, Aβ40, Aβ42) in DLB, Alzheimer’s disease (AD), and cognitively normal controls. Methods CSF from patients with DLB (n = 72; age 68 ± 6 years; 10%F; Mini-mental State examination (MMSE) 23 ± 4), AD (n = 38; age 68 ± 6 years; 8%F; MMSE 22 ± 5), and cognitively normal controls (n = 38; age 67 ± 7 years; 13%F; MMSE 29 ± 2) was analyzed using the Meso Scale Discovery assay for human Aβ peptides. We performed general linear models to compare CSF Aβ peptide levels between groups. Associations between CSF Aβ peptides and MMSE score at baseline and longitudinal changes over time were assessed with linear mixed models. Results For all three CSF Aβ peptides and compared to controls (Aβ38 2676 ± 703 pg/ml, Aβ40 6243 ± 1500 pg/ml, and Aβ42 692 ± 205 pg/ml), we observed lower levels in DLB (Aβ38 2247 ± 638, Aβ40 5432 ± 1340, and Aβ42 441 ± 185, p < 0.05), whereas AD patients showed only lower Aβ42 levels (304 ± 71, p < 0.001). The observed differences in Aβ38 and Aβ40 were independent of co-morbid AD pathology (CSF tau/Aβ42 > 0.52) and APOE genotype. Finally, lower Aβ peptide levels were associated with lower MMSE score (β = 1.02–1.11, p < 0.05). Conclusion We demonstrated different profiles of CSF Aβ reduction in DLB and AD. In particular, while AD is characterized by an isolated drop in Aβ42, DLB comes with reductions in Aβ38, Aβ40, and Aβ42. This suggests that amyloid metabolism is affected in DLB, even in the absence of co-morbid AD pathology.

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Cerebrospinal Fluid Markers in Dementia With Lewy Bodies Compared With Alzheimer Disease

Archives of Neurology ◽

10.1001/archneur.60.9.1218 ◽

2003 ◽

Vol 60 (9) ◽

Cited By ~ 76

Author(s):

Estrella Gómez-Tortosa ◽

Isabel Gonzalo ◽

Samira Fanjul ◽

Maria José Sainz ◽

Susana Cantarero ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Alzheimer Disease ◽

Dementia With Lewy Bodies ◽

Lewy Bodies

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Alpha-synuclein in the Cerebrospinal Fluid Differentiates Synucleinopathies (Parkinson Disease, Dementia With Lewy Bodies, Multiple System Atrophy) From Alzheimer Disease

Alzheimer Disease & Associated Disorders ◽

10.1097/wad.0b013e31823899cc ◽

2012 ◽

Vol 26 (3) ◽

pp. 213-216 ◽

Cited By ~ 77

Author(s):

Fuyuki Tateno ◽

Ryuji Sakakibara ◽

Takayuki Kawai ◽

Masahiko Kishi ◽

Takeyoshi Murano

Keyword(s):

Cerebrospinal Fluid ◽

Alzheimer Disease ◽

Multiple System Atrophy ◽

Parkinson Disease ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Alpha Synuclein

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

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317519869700 ◽

2019 ◽

Vol 34 (7-8) ◽

pp. 421-432

Author(s):

Ioannis Mavroudis ◽

Foivos Petridis ◽

Dimitrios Kazis

Keyword(s):

Cerebrospinal Fluid ◽

Alzheimer Disease ◽

Dementia With Lewy Bodies ◽

Autonomic Function ◽

Neurodegenerative Disorder ◽

Lewy Bodies ◽

Behavioral Changes ◽

Western World ◽

Csf Biomarkers ◽

Fluid Imaging

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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Glial fibrillar acidic protein in the cerebrospinal fluid of Alzheimer's disease, dementia with Lewy bodies, and frontotemporal lobar degeneration

Journal of Neurochemistry ◽

10.1111/jnc.13399 ◽

2015 ◽

Vol 136 (2) ◽

pp. 258-261 ◽

Cited By ~ 33

Author(s):

Aiko Ishiki ◽

Maki Kamada ◽

Yuki Kawamura ◽

Chiaki Terao ◽

Fumiko Shimoda ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Frontotemporal Lobar Degeneration ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Acidic Protein ◽

Alzheimer’S Disease Dementia ◽

Glial Fibrillar Acidic Protein

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A Detailed Phenomenological Comparison of Complex Visual Hallucinations in Dementia With Lewy Bodies and Alzheimer's Disease

International Psychogeriatrics ◽

10.1017/s1041610297004523 ◽

1997 ◽

Vol 9 (4) ◽

pp. 381-388 ◽

Cited By ~ 38

Author(s):

Clive Ballard ◽

Ian McKeith ◽

Richard Harrison ◽

John O'Brien ◽

Peter Thompson ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Time Of Day ◽

Visual Hallucinations ◽

Dementia Patients ◽

Core Feature ◽

Definition Of

Visual hallucinations (VH) are a core feature of dementia with Lewy bodies (DLB), but little is known about their phenomenology. A total of 73 dementia patients (42 DLB, 30 Alzheimer's disease [AD], 1 undiagnosed) in contact with clinical services were assessed with a detailed standardized inventory. DLB was diagnosed according to the criteria of McKeith and colleagues, AD was diagnosed using the NINCDS-ADRDA criteria. Autopsy confirmation has been obtained when possible. VH were defined using the definition of Burns and colleagues. Detailed descriptions of hallucinatory experiences were recorded. Annual follow-up interviews were undertaken. The clinical diagnosis has been confirmed in 18 of the 19 cases that have come to autopsy. A total of 93% of DLB patients and 27% of AD patients experienced VH. DLB patients were significantly more likely to experience multiple VH that persisted over follow-up. They were significantly more likely to hear their VH speak but there were no significant differences in the other phenomenological characteristics including whether the hallucinations moved, the time of day that they were experienced, their size, the degree of insight, and whether they were complete. VH may be more likely to be multiple, to speak, and to be persistent in DLB patients. These characteristics could potentially aid accurate diagnosis.

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