Neuropathological Changes in Dementia With Lewy Bodies and the Cingulate Island Sign

Abstract

The cingulate island sign (CIS) refers to the relative sparing of metabolism in the posterior cingulate cortex (PCC) and represents an important biomarker in distinguishing dementia with Lewy bodies (DLB) from Alzheimer disease (AD). The underlying basis of the CIS is unknown; therefore, our aim was to investigate which neurodegenerative changes underpin the formation of CIS. Using quantitative neuropathology, α-synuclein, phosphorylated Tau, and amyloid-β pathology was assessed in 12 DLB, 9 AD and 6 age-matched control patients in the anterior cingulate (ACC), midcingulate, PCC, precuneus/cuneus and parahippocampal gyrus. All participants had undergone 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography imaging during life to define the presence or absence of CIS. In the DLB group, no significant correlations were observed between CIS ratios and neurodegenerative pathology in PCC. In DLB, however, the ACC showed lower HMPAO uptake, as well as significantly higher α-synuclein and amyloid-β burden compared with PCC, possibly underlying the relative preservation of perfusion in PCC when compared with ACC. Our findings suggest that neurodegenerative pathology does not directly correlate with the CIS in DLB, and other metabolic or pathological changes are therefore more likely to be relevant for the development of the CIS.

Dissociation of tau pathology and neuronal hypometabolism within the ATN framework of Alzheimer’s disease

“…We emphasize that this analysis was exploratory and requires further comprehensive validation. The cortical susceptible group harbored higher cingulate island ratio and worse visuospatial processing and trended toward greater frequency of hallucinations, all supportive of concomitant LBD 18,19 . In contrast, the limbic susceptible group had the greatest average age among groups (78.9 ± 6.1 years) and a pattern of MTLpredominant hypometabolism with asymmetry, all features that have been associated with LATE 21,22 .…”

“…We tested imaging and clinical markers of α-synuclein (Lewy body) pathology in the cortical susceptible group. A well-studied, potential indicator of Lewy Body Disease (LBD) is the cingulate island sign [18][19][20] , the relative sparing of 18 F-FDG SUVR in the posterior cingulate cortex relative to precuneus and cuneus (Fig. 5a).…”

“…The median regional correlation coefficient between T/N S and T/N M residuals was 0.29, suggesting that while T/N S and T/N M relationships are similar, they may provide some unique information. For example, metabolism may be more sensitive to Lewy body pathology than structure 18,19 . Likewise, metabolism may reflect aspects of functional reserve and synaptic activity not captured by structural markers while, alternatively, structure may be less affected by non-disease related functional variability than metabolism.…”

“…AD can present with multiple proteinopathies, including αsynuclein 18 and TDP-43 inclusions 23 . While there are not yet well-established biomarkers for these pathologies, 18 F-FDG PET studies have provided patterns probabilistically related to both entities [19][20][21][22] . We emphasize that this analysis was exploratory and requires further comprehensive validation.…”

Neural basis of impaired narrative discourse comprehension in prodromal and mild dementia with lewy bodies

“…At the brain level, Lewy body spectrum disorders (LBSD) such as PD, Parkinson’s disease with dementia (PDD) and DLB are characterized by diffuse brain lesions related to the progression of the abnormal aggregation of alpha-synuclein, associated with pervasive cellular death in dopaminergic regions of the brain. However, contrary to other synucleinopathies, like PD, the pattern of alteration seems to spread to more cortical regions, such as the insula ( Roquet et al, 2017 ), and to be associated with both phosphorylated tau and beta-amyloid deposits in the affected regions ( Patterson et al, 2019 ).…”