Neocortical Lewy bodies are associated with impaired odor identification in community-dwelling elders without clinical PD

Nag, Sukriti; Yu, Lei; VanderHorst, Veronique; Schneider, Julie A.; Bennett, David A.; Buchman, Aron S.; Wilson, Robert S.

doi:10.1007/s00415-019-09540-5

Cited by 19 publications

(20 citation statements)

References 67 publications

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“…The apparently closer association between hyposmia and bodyfirst LBD can be explained in two ways. Recent postmortem studies have reported that hyposmia, measured before death, correlates with the total burden of CNS Lewy pathology, but show little or no correlation with the burden of Lewy pathology in the OB itself 41,42 . This means that hyposmia is a symptom of widespread CNS Lewy pathology, but not so much of pathology in the OB per se.…”

Section: Discussionmentioning

confidence: 99%

A postmortem study suggests a revision of the dual-hit hypothesis of Parkinson’s disease

Borghammer

Just

Horsager

et al. 2022

npj Parkinsons Dis.

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The dual-hit hypothesis of Parkinson’s disease (PD) originally postulated that a neurotropic pathogen leads to formation of α-synuclein pathology in the olfactory bulb (OB) and dorsal motor nucleus of the vagus (DMV) and then invades the brain from these two entry points. Little work has been conducted to validate an important underlying premise for the dual-hit hypothesis, namely that the initial Lewy pathology does arise simultaneously in the OB and the enteric nervous system (ENS) plexuses and DMV at the earliest disease stage. We conducted a focused re-analysis of two postmortem datasets, which included large numbers of mild Lewy body disease (LBD) cases. We found that cases with α-synuclein pathology restricted to the peripheral autonomic nervous system and/or lower brainstem (early body-first LBD cases) very rarely had any OB pathology, suggesting that Lewy pathology commonly arises in the ENS without concomitant involvement of the OB. In contrast, cases with mild amygdala-predominant Lewy pathology (early brain-first LBD cases) nearly always showed OB pathology. This is compatible with the first pathology being triggered in the OB or amygdala followed by secondary spreading to connected structures, but without early involvement of the ENS or lower brainstem. These observations support that the pathologic process starts in either the olfactory bulb or the ENS, but rarely in the olfactory bulb and gut simultaneously. More studies on neuropathological datasets are warranted to reproduce these findings. The agreement between the revised single-hit hypothesis and the recently proposed brain-first vs. body-first model of LBD is discussed.

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Section: Discussionmentioning

confidence: 99%

A postmortem study suggests a revision of the dual-hit hypothesis of Parkinson’s disease

Borghammer

Just

Horsager

et al. 2022

npj Parkinsons Dis.

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“…In addition, many neuropsychiatric disorders, such as Parkinson's disease (Hoyles and Sharma, 2013), dementia with Lewy bodies (Mahlknecht et al, 2015), and schizophrenia (Kamath et al, 2019), are reported to be associated with OI impairment. In addition to AD pathologic alterations, alpha-synucleinopathy of Parkinson's disease and dementia with Lewy bodies in the cortical brain and olfactory-related regions are also observed and are supported by convincing evidence (Wilson et al, 2007;Arnold et al, 2010;Nag et al, 2019).…”

Section: Discussionmentioning

confidence: 73%

Association of Odor Identification Ability With Amyloid-β and Tau Burden: A Systematic Review and Meta-Analysis

Fan

et al. 2020

Front. Neurosci.

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Background: The associations between olfactory identification (OI) ability and the Alzheimer's disease biomarkers were not clear.Objective: This meta-analysis aimed to examine the associations between OI and Aβ and tau burden.Methods: Electronic databases (PubMed, Embase, PsycINFO, and Google Scholar) were searched until June 2019 to identify studies that reported correlation coefficients or regression coefficients between OI and Aβ or tau levels measured by positron emission tomography (PET) or cerebrospinal fluid (CSF). Pooled Pearson correlation coefficients were computed for the PET imaging and CSF biomarkers, with subgroup analysis for subjects classified into different groups.Results: Nine studies met the inclusion criteria. Of these, five studies (N = 494) involved Aβ PET, one involved tau PET (N = 26), and four involved CSF Aβ or tau (N = 345). OI was negatively associated with Aβ PET in the mixed (r = −0.25, P = 0.008) and cognitively normal groups (r = −0.15, P = 0.004) but not in the mild cognitive impairment group. A similar association with CSF total tau in the mixed group was also observed. No association was found between OI and CSF phosphorylated tau or Aβ42 in the subgroup analysis of the CSF biomarkers. Due to a lack of data, no pooled r value could be computed for the association between the OI and tau PET.Conclusion: The associations between OI ability and Aβ and CSF tau burden in older adults are negligible. While current evidence does not support the association, further studies using PET tau imaging are warranted.

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“… 34 , 42 Braak stage of illness, which captures neurofibrillary tangle pathology, was categorized as III or less or IV or greater due to the small number of cases in individual Braak stages II, III, and VI. 43 Lewy Body disease and infarcts were considered present or absent. 36 Global pathology, amyloid burden, diffuse and neuritic plaques, and neurofibrillary tangle density and burden were analyzed as continuous outcomes.…”

Section: Detailed Methods and Resultsmentioning

confidence: 99%

Association of vitamin K with cognitive decline and neuropathology in community‐dwelling older persons

Booth

Shea

Barger

et al. 2022

A&D Transl Res & Clin Interv

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Higher vitamin K intakes have been associated with better cognitive function, suggestive of a vitamin K mechanistic effect or simply reflective of a healthy diet. To test the hypothesis that brain vitamin K is linked to cognitive decline and dementia, vitamin K concentrations were measured in four brain regions, and their associations with cognitive and neuropathological outcomes were estimated in 325 decedents of the Rush Memory and Aging Project. Menaquinone‐4 (MK4) was the main vitamin K form in the brain regions evaluated. Higher brain MK4 concentrations were associated with a 17% to 20% lower odds of dementia or mild cognitive impairment (MCI) ( P ‐value < .014), with a 14% to 16% lower odds of Braak stage ≥IV ( P ‐value < 0.045), with lower Alzheimer's disease global pathology scores and fewer neuronal neurofibrillary tangles ( P ‐value < 0.012). These findings provide new and compelling evidence implicating vitamin K in neuropathology underlying cognitive decline and dementia.

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Neocortical Lewy bodies are associated with impaired odor identification in community-dwelling elders without clinical PD

Cited by 19 publications

References 67 publications

A postmortem study suggests a revision of the dual-hit hypothesis of Parkinson’s disease

A postmortem study suggests a revision of the dual-hit hypothesis of Parkinson’s disease

Association of Odor Identification Ability With Amyloid-β and Tau Burden: A Systematic Review and Meta-Analysis

Association of vitamin K with cognitive decline and neuropathology in community‐dwelling older persons

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