Locus Coeruleus Malfunction Is Linked to Psychopathology in Prodromal Dementia With Lewy Bodies

Psychiatric Symptoms ◽

Lewy Bodies ◽

Neuronal Loss ◽

Alpha Synuclein ◽

Narrative Review ◽

Noradrenergic Neurons ◽

Prodromal Dementia ◽

The Relationship

Background: The locus coeruleus (LC) is a nucleus in the human brainstem with a variety of noradrenaline-driven functions involved in cognition, emotions, and perception. Dementia with Lewy bodies (DLB) constitutes a neurodegenerative disease involving deposits of alpha-synuclein, first appearing in the brainstem. The goal of this narrative review is to delineate the relationship between the expression of psychiatric symptoms as an early-onset of DLB and the degeneration of the LC's noradrenaline system.Methods: We searched in PubMed for relevant articles concerning LC degeneration and psychiatric symptoms in prodromal DLB in this narrative review. We rely on the McKeith criteria for prodromal psychiatric DLB.Results: We found four studies that document neuronal loss, deposits of Lewy bodies and other hints for neurodegeneration in the LC in patients with DLB. Furthermore, we reviewed theories and studies on how the degenerated noradrenaline LC system contributes to psychiatric DLB's phenotype. We hypothesized how anxiety, hallucinations, delusions, and depressive symptoms might occur in DLB patients due to degenerated noradrenergic neurons entailing consecutive altered noradrenergic transmission in the LC's projection areas.Conclusions: LC degeneration in prodromal DLB might cause psychiatric symptoms as the first and non-motor manifestation of DLB, as the LC is affected earlier by degeneration than are dopaminergic structures such as the substantia nigra, which are impaired later in the disease course.

Prodromal Dementia With Lewy Bodies: Evolution of Symptoms and Predictors of Dementia Onset

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/08919887211023586 ◽

2021 ◽

pp. 089198872110235

Author(s):

Kathryn A. Wyman-Chick ◽

Lauren R. O’Keefe ◽

Daniel Weintraub ◽

Melissa J. Armstrong ◽

Michael Rosenbloom ◽

...

Keyword(s):

Clinical Features ◽

Clinical Symptoms ◽

Neuropsychiatric Symptoms ◽

Lewy Bodies ◽

Rem Sleep Behavior Disorder ◽

Data Set ◽

Wide Range ◽

Prodromal Dementia ◽

Dementia Onset

Background: Research criteria for prodromal dementia with Lewy bodies (DLB) were published in 2020, but little is known regarding prodromal DLB in clinical settings. Methods: We identified non-demented participants without neurodegenerative disease from the National Alzheimer’s Coordinating Center Uniform Data Set who converted to DLB at a subsequent visit. Prevalence of neuropsychiatric and motor symptoms were examined up to 5 years prior to DLB diagnosis. Results: The sample included 116 participants clinically diagnosed with DLB and 348 age and sex-matched (1:3) Healthy Controls. Motor slowing was present in approximately 70% of participants 3 years prior to DLB diagnosis. In the prodromal phase, 50% of DLB participants demonstrated gait disorder, 70% had rigidity, 20% endorsed visual hallucinations, and over 50% of participants endorsed REM sleep behavior disorder. Apathy, depression, and anxiety were common prodromal neuropsychiatric symptoms. The presence of 1+ core clinical features of DLB in combination with apathy, depression, or anxiety resulted in the greatest AUC (0.815; 95% CI: 0.767, 0.865) for distinguishing HC from prodromal DLB 1 year prior to diagnosis. The presence of 2+ core clinical features was also accurate in differentiating between groups (AUC = 0.806; 95% CI: 0.756, 0.855). Conclusion: A wide range of motor, neuropsychiatric and other core clinical symptoms are common in prodromal DLB. A combination of core clinical features, neuropsychiatric symptoms and cognitive impairment can accurately differentiate DLB from normal aging prior to dementia onset.

ALPHA SYNUCLEIN IMMUNOREACTIVITY IN DEMENTIA WITH LEWY BODIES

Journal of Neuropathology & Experimental Neurology ◽

10.1097/00005072-199905000-00188 ◽

1999 ◽

Vol 58 (5) ◽

pp. 553

Author(s):

E Gómez-Tortosa ◽

K L Newell ◽

M C Irizarry ◽

M Albert ◽

J H Growdon ◽

...

Keyword(s):

Lewy Bodies ◽

Alpha Synuclein

[P1-243]: ALPHA-SYNUCLEIN SPECIES AS POTENTIAL CSF BIOMARKERS FOR DEMENTIA WITH LEWY BODIES

Alzheimer s & Dementia ◽

10.1016/j.jalz.2017.06.063 ◽

2017 ◽

Vol 13 (7S_Part_7) ◽

pp. P338-P338 ◽

Cited By ~ 2

Author(s):

Inger van Steenoven ◽

Nour K. Majbour ◽

Nishant N. Vaikath ◽

Henk W. Berendse ◽

Wiesje M. van der Flier ◽

...

Keyword(s):

Lewy Bodies ◽

Alpha Synuclein ◽

Csf Biomarkers

Early diagnosis of prodromal dementia with Lewy bodies using clinical history of probable REM sleep behaviour disorder and cardiac 123 I‐MIBG scintigraphy in memory clinics

Psychogeriatrics ◽

10.1111/psyg.12662 ◽

2021 ◽

Author(s):

Hiroshige Fujishiro ◽

Kazumi Ota ◽

Mayumi Yamagata ◽

Tatsuya Ito ◽

Sotaro Hieda ◽

...

Keyword(s):

Lewy Bodies ◽

Clinical History ◽

Mibg Scintigraphy ◽

Behaviour Disorder ◽

Sleep Behaviour ◽

Rem Sleep Behaviour Disorder ◽

Memory Clinics ◽

History Of ◽

Lost in a Dream

Sleep Disorders ◽

10.1093/med/9780190671099.003.0020 ◽

2019 ◽

pp. 381-396

Author(s):

Carlos L. Rodriguez ◽

Babak Tousi

Keyword(s):

Motor Neurons ◽

Neurodegenerative Disorders ◽

Neurodegenerative Disorder ◽

Lewy Bodies ◽

Behavior Disorder ◽

Sleep Behavior ◽

The Relationship ◽

Over Time

Rapid-eye-movement sleep behavior disorder (RBD) is a parasomnia that is closely associated with neurodegenerative disorders. RBD is usually caused by neurodegeneration within the brainstem that disables the system responsible for immobilizing skeletal muscles during REM sleep and thus permits motor neurons to activate these muscles during dreaming. The underlying source of the brainstem neurodegeneration spreads over time to other central nervous system regions until it has sufficiently evolved to permit clinical recognition of the underlying neurodegenerative disorder. Longitudinal follow-up of patients with RBD has demonstrated that most patients subsequently develop some neurodegenerative disorder years later, particularly the synucleinopathies. We review the relationship between RBD and dementia with Lewy bodies, which is one of the synucleinopathies. The management of RBD is reviewed with discussion of the relevant considerations in patients with dementia with Lewy bodies.

P1-180: Prodromal and Non-Prodromal Dementia with Lewy Bodies and Alzheimer's Disease: A Multimodal Mri Approach

Alzheimer s & Dementia ◽

10.1016/j.jalz.2016.06.928 ◽

2016 ◽

Vol 12 ◽

pp. P473-P473

Author(s):

Frederic Blanc ◽

Daniel Roquet ◽

Vincent Noblet ◽

Benjamin Cretin ◽

Julien Lamy ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Lewy Bodies ◽

Multimodal Mri ◽

O5-03-03: PREVALENCE OF NEUROPSYCHIATRIC AND MOTOR SYMPTOMS IN PRODROMAL DEMENTIA WITH LEWY BODIES

Alzheimer s & Dementia ◽

10.1016/j.jalz.2018.06.3009 ◽

2006 ◽

Vol 14 (7S_Part_31) ◽

pp. P1645-P1646

Author(s):

Kathryn A. Wyman-Chick ◽

Lauren O. Erickson ◽

Michael H. Rosenbloom ◽

Terry R. Barclay ◽

Julia C. Johnson ◽

...

Keyword(s):

Lewy Bodies ◽

Motor Symptoms ◽

Imaging in prodromal dementia with Lewy bodies: Where do we stand?

International Journal of Geriatric Psychiatry ◽

10.1002/gps.5071 ◽

2019 ◽

Vol 34 (5) ◽

pp. 635-646 ◽

Cited By ~ 7

Author(s):

Rory Durcan ◽

Paul Donaghy ◽

Curtis Osborne ◽

John‐Paul Taylor ◽

Alan J. Thomas

Keyword(s):

Lewy Bodies ◽

Diagnostic accuracy of dopaminergic imaging in prodromal dementia with Lewy bodies

Psychological Medicine ◽

10.1017/s0033291718000995 ◽

2018 ◽

Vol 49 (3) ◽

pp. 396-402 ◽

Cited By ~ 15

Author(s):

Alan J. Thomas ◽

Paul Donaghy ◽

Gemma Roberts ◽

Sean J. Colloby ◽

Nicky A. Barnett ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Lewy Body ◽

Lewy Bodies ◽

Lewy Body Disease ◽

High Specificity ◽

Diagnostic Confidence ◽

Neuropsychological Assessments ◽

Diagnostic Symptoms ◽

AbstractBackgroundDopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.MethodsWe recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.ResultsThe sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).ConclusionsDopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.