Hippocampal subfield pathologic burden in Lewy body diseases <i>vs</i>. Alzheimer’s disease

Coughlin, David G.; Ittyerah, Ranjit; Peterson, Claire; Phillips, Jeffrey S.; Miller, Simon; Rascovsky, Katya; Weintraub, Daniel; Siderowf, Andrew; Duda, John E.; Hurtig, Howard I.; Wolk, David A.; McMillan, Corey T.; Yushkevich, Paul A.; Grossman, Murray; Lee, Edward B.; Trojanowski, John Q.; Irwin, David J.

doi:10.1111/nan.12659

Cited by 26 publications

(30 citation statements)

References 75 publications

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“…The noradrenergic LC system often becomes degenerated early in both alpha-synucleinopathies such as Parkinson's disease (PD) (Solopchuk et al, 2018;Li et al, 2019), and ß-amyloidopathies like Alzheimer's disease (AD) (Zarow et al, 2003;Hou et al, 2021). Both diseases are closely related to Lewy body pathology, as mixed pathologies can coexist in patients with cognitive impairment (Coughlin et al, 2020). Lewy body dementia includes the terms PD dementia and DLB (Haider et al, 2020).…”

Section: Degeneration Of the Locus Coeruleus In Dementia With Lewy Bomentioning

confidence: 99%

“…There is another prodromal DLB subtype besides psychiatric prodromal DLB that is characterized by mild cognitive impairment (McKeith et al, 2020 ). Episodic memory dysfunction exists in DLB, and might be related to the spread of alpha synuclein pathology in hippocampal subfields CA2/3 (Coughlin et al, 2020 ) as relevant structures for memory formation. Furthermore, Coughlin et al ( 2020 ) demonstrated that hippocampal tau protein within the hippocampus subregion CA2/3 correlated negatively with memory function in patients with LBD.…”

Section: Noradrenergic Mechanisms Inducing Psychiatric Symptoms In Prmentioning

confidence: 99%

“…Episodic memory dysfunction exists in DLB, and might be related to the spread of alpha synuclein pathology in hippocampal subfields CA2/3 (Coughlin et al, 2020 ) as relevant structures for memory formation. Furthermore, Coughlin et al ( 2020 ) demonstrated that hippocampal tau protein within the hippocampus subregion CA2/3 correlated negatively with memory function in patients with LBD. Given the LC's pivotal role in memory processing at various memory stages (Sara, 2015 ; Hansen, 2017 ) as shown in animal models (Hansen and Manahan-Vaughan, 2015a , b ) and humans (Jacobs et al, 2015 , 2020 ) it is likely that LC degeneration with its LC terminals affect hippocampal memory-processing in prodromal DLB patients.…”

Section: Noradrenergic Mechanisms Inducing Psychiatric Symptoms In Prmentioning

confidence: 99%

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

Hansen

2021

Front. Aging Neurosci.

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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.

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Section: Degeneration Of the Locus Coeruleus In Dementia With Lewy Bomentioning

confidence: 99%

Section: Noradrenergic Mechanisms Inducing Psychiatric Symptoms In Prmentioning

confidence: 99%

Section: Noradrenergic Mechanisms Inducing Psychiatric Symptoms In Prmentioning

confidence: 99%

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

Hansen

2021

Front. Aging Neurosci.

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“…While in AD, amyloid beta (Aβ), and tau play a central role, in DLB and PD -synuclein ( -syn) is a key mediator [2][3][4][5][6] . However, -syn has been shown to accumulate in the brains during aging and in AD and in DLB, Aβ and tau are also found in conjunction with -syn in selected brain regions [7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

Aging exacerbates the brain inflammatory micro-environment contributing to α-synuclein pathology and functional deficits a mouse model of DLB/PD

Iba

McDevitt

Kim

et al. 2021

Preprint

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ɑ-synuclein (ɑ-syn) progressively accumulates in age related neurodegenerative diseases such as Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB). Although ɑ-syn spreading has been extensively investigated, the role of aging in the manifestation of disease remains unclear. Thus, we explored the role of aging in the pathogenesis of synucleinopathies in a mouse model of DLB/PD initiated by intrastiatal injection of ɑ-syn preformed fibrils (pff). We found that aged mice showed more extensive accumulation of ɑ-syn and behavioral deficits that was associated with greater infiltration of T cells and microgliosis. Microglial inflammatory gene expression induced by ɑ-syn-pff injection in young mice had hallmarks of aged microglia, indicating that enhanced age-associated pathologies may result from inflammatory synergy between aging and the effects of ɑ-syn aggregation. We propose that aging related inflammation influences outcomes of pathological spreading of ɑ-syn and suggests that targeting immune responses might be important in developing treatments for DLB/PD.

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“…Suspected DLB patients exhibit a neuropsychological profile suggesting Lewy Body pathology, such as visuospatial deficits or attentional executive dysfunction with relatively intact episodic memory function. Though some DLB patients also show memory deficits ( Coughlin et al, 2020 ), which makes it difficult to distinguish them from patients with Alzheimer dementia. To diagnose DLB according to McKeith’s criteria ( McKeith et al, 2017 ), the patients must display a progressive dementia interfering with daily living activities.…”

Section: Introductionmentioning

confidence: 99%

Assessing Nigrostriatal Dopaminergic Pathways via 123I-FP-CIT SPECT in Dementia With Lewy Bodies in a Psychiatric Patient Cohort

Hansen

Lange

Timäus

et al. 2021

Front. Aging Neurosci.

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Background(123)-I-2-ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortro- pane single photon emission computed tomography (123I-FP-CIT SPECT) was validated to distinguish Alzheimer’s dementia from dementia with Lewy Bodies (DLB) by European medical agencies. Little evidence exists that validates 123 I-FP-CIT SPECT as a supplementary method to diagnose probable DLB in a psychiatric cohort of patients with psychiatric symptomatology and suspected DLB. We aim to elucidate differences in the clinical phenotype of DLB between those patients with and those without a positive 123 I-FP-CIT SPECT indicating a nigrostriatal deficit.MethodsTo investigate this, we included 67 patients from the Department of Psychiatry and Psychotherapy at University Medical Center Göttingen (UMG) in our study who had undergone 123I-FP-CIT SPECT in the Department of Nuclear Medicine (UMG) by evaluating their patient files.Results55% with a positive-123I-FP-CIT SPECT and probable DLB after the 123I-FP-CIT SPECT exhibited psychiatric features. The number of probable DLB patients in those exhibiting psychiatric symptoms was higher post-123I-FP-CIT SPECT than pre-123I-FP-CIT SPECT assessed cross-sectionally over a 6-year period (p < 0.05). In addition, prodromal DLB and prodromal DLB patients with a psychiatric-phenotype yielded higher numbers post-123I-FP-CIT SPECT than pre-123I-FP-CIT SPECT (p < 0.05). Furthermore, we discovered no phenotypical differences between those DLB patients with a positive and those with a negative 123I-FP-CIT SPECT. 123I-FP-CIT SPECT-positive DLB patients in our psychiatric cohort revealed a psychiatric onset more often (52%); DLB was less often characterized by an MCI onset (26%) (p < 0.005).ConclusionsOur findings support 123I-FP-CIT SPECT as an adjuvant tool for improving the diagnosis of probable DLB and prodromal DLB in a cohort of psychiatric patients with often concomitant psychiatric symptomatology. The psychiatric-onset is more frequent than an MCI-onset in DLB patients presenting nigrostriatal dysfunction, giving us an indication of the relevance of deep clinical phenotyping in memory clinics that includes the assessment of psychopathology.

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Hippocampal subfield pathologic burden in Lewy body diseases vs. Alzheimer’s disease

Cited by 26 publications

References 75 publications

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

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

Aging exacerbates the brain inflammatory micro-environment contributing to α-synuclein pathology and functional deficits a mouse model of DLB/PD

Assessing Nigrostriatal Dopaminergic Pathways via 123I-FP-CIT SPECT in Dementia With Lewy Bodies in a Psychiatric Patient Cohort

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