Dementia Atrophy Research Articles

Cerebrovascular and Alzheimer's disease biomarkers in dementia with Lewy bodies and other dementias.

Co-pathologies are common in dementia with Lewy bodies and other dementia disorders. We investigated cerebrovascular and Alzheimer's disease co-pathologies in patients with dementia with Lewy bodies in comparison with patients with mild cognitive impairment, Alzheimer's disease, mixed dementia, vascular dementia or Parkinson's disease with dementia and cognitively unimpaired participants. We assessed the association of biomarkers of cerebrovascular and Alzheimer's disease co-pathologies with medial temporal atrophy and global cognitive performance. Additionally, we evaluated whether the findings were specific to dementia with Lewy bodies. We gathered a multi-cohort dataset of 4549 participants (dementia with Lewy bodies = 331, cognitively unimpaired = 1505, mild cognitive impairment = 1489, Alzheimer's disease = 708, mixed dementia = 268, vascular dementia = 148, Parkinson's disease with dementia = 120) from the MemClin Study, Karolinska Imaging in Dementia Study, Gothenburg H70 Birth Cohort Studies and the European DLB Consortium. Cerebrovascular co-pathology was assessed with visual ratings of white matter hyperintensities using the Fazekas scale through structural imaging. Alzheimer's disease biomarkers of β-amyloid and phosphorylated tau were assessed in the cerebrospinal fluid for a subsample (N = 2191). Medial temporal atrophy was assessed with visual ratings and global cognition with the mini-mental state examination. Differences and associations were assessed through regression models, including interaction terms. In dementia with Lewy bodies, 43% had a high white matter hyperintensity load, which was significantly higher than that in cognitively unimpaired (14%), mild cognitive impairment (26%) and Alzheimer's disease (27%), but lower than that in vascular dementia (62%). In dementia with Lewy bodies, white matter hyperintensities were associated with medial temporal atrophy, and the interaction term showed that this association was stronger than that in cognitively unimpaired and mixed dementia. However, the association between white matter hyperintensities and medial temporal atrophy was non-significant when β-amyloid was included in the model. Instead, β-amyloid predicted medial temporal atrophy in dementia with Lewy bodies, in contrast to the findings in mild cognitive impairment where medial temporal atrophy scores were independent of β-amyloid. Dementia with Lewy bodies had the lowest performance on global cognition, but this was not associated with white matter hyperintensities. In Alzheimer's disease, global cognitive performance was lower in patients with more white matter hyperintensities. We conclude that white matter hyperintensities are common in dementia with Lewy bodies and are associated with more atrophy in medial temporal lobes, but this association depended on β-amyloid-related pathology in our cohort. The associations between biomarkers were overall stronger in dementia with Lewy bodies than in some of the other diagnostic groups.

MRI-based axis-referenced morphometric model corresponding to lamellar organization for assessing hippocampal atrophy in dementia.

Research on the local hippocampal atrophy for early detection of dementia has gained considerable attention. However, accurately quantifying subtle atrophy remains challenging in existing morphological methods due to the lack of consistent biological correspondence with the complex curving regions like the hippocampal head. Thereby, this article presents an innovative axis-referenced morphometric model (ARMM) that follows the anatomical lamellar organization of the hippocampus, which capture its precise and consistent longitudinal curving trajectory. Specifically, we establish an "axis-referenced coordinate system" based on a 7 T ex vivo hippocampal atlas following its entire curving longitudinal axis and orthogonal distributed lamellae. We then align individual hippocampi by deforming this template coordinate system to target spaces using boundary-guided diffeomorphic transformation, while ensuring that the lamellar vectors adhere to the constraint of medial-axis geometry. Finally, we measure local thickness and curvatures based on the coordinate system and boundary surface reconstructed from vector tips. The morphometric accuracy is evaluated by comparing reconstructed surfaces with those directly extracted from 7 T and 3 T MRI hippocampi. The results demonstrate that ARMM achieves the best performance, particularly in the curving head, surpassing the state-of-the-art morphological models. Additionally, morphological measurements from ARMM exhibit higher discriminatory power in distinguishing early Alzheimer's disease from mild cognitive impairment compared to volume-based measurements. Overall, the ARMM offers a precise morphometric assessment of hippocampal morphology on MR images, and sheds light on discovering potential image markers for neurodegeneration associated with hippocampal impairment.

Sex differences in brain atrophy in dementia with Lewy bodies.

Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n=327; 73±8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n=165; 69±9 years, 72% males). We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.

Brainstem atrophy in dementia with Lewy bodies compared with progressive supranuclear palsy and Parkinson’s disease on MRI

BackgroundAlthough Dementia with Lewy bodies (DLB) is the second most common form of dementia in elderly patients, it remains underdiagnosed compared with Alzheimer's (AD) and Parkinson's diseases (PD). This may be explained by overlapping clinical symptoms, e.g. Parkinsonism. While current MRI research focuses primarily on atrophy patterns of the frontal and temporal lobes, we focus on brainstem characteristics of DLB. In particular, we focused on brainstem atrophy patterns distinguishing DLB from Progressive Supranuclear Palsy (PSP) and PD based as the most common differential diagnoses.MethodsWe identified patients diagnosed with DLB, PD, PSP, and a control group (CTRL) in our psychiatric and neurological archives. All patients with competing diagnoses and without a high-quality T1 MPRAGE 3D dataset were excluded. We assessed atrophy patterns in all patients (1) manually and (2) using FastSurfer’s segmentation algorithm in combination with FreeSurfer’s brainstem volumetric calculations. We compared classical measurement methods and ratios with automated volumetric approaches.ResultsOne hundred two patients were enrolled and evaluated in this study. Patients with DLB (n = 37) showed on average less atrophy of the brainstem than patients with PSP (n = 21), but a significantly more pronounced atrophy than patients with PD (n = 36) and the control group (CTRL, n = 8). The mean measured sagittal diameters of the midbrain were 8.17 ± 1.06 mm (mean ± standard deviation) for PSP, 9.45 ± 0.95 mm for DLB, 10.37 ± 0.99 mm for PD and 10.74 ± 0.70 for CTRL. The mean measured areas of the midbrain were 81 ± 18 mm2 for PSP, 105 ± 17 mm2 for DLB, 130 ± 26 mm2 for PD and 135 ± 23 mm2 for CTRL. The mean segmented volumes of the midbrain were 5595 ± 680 mm3 for PSP, 6051 ± 566 mm3 for DLB, 6646 ± 802 mm3 for PD and 6882 ± 844 mm3 for CTRL. The calculated midbrain pons ratios did not show superiority over the absolute measurements of the midbrain for distinguishing PSP from DLB. Because of the relatively uniform atrophy throughout the brainstem, the ratios were not suitable for distinguishing DLB from PD.ConclusionsDLB patients exhibit homogenous atrophy of the brainstem and can be distinguished from patients with PSP and PD by both manual measurement methods and automated volume segmentation using absolute values or ratios.

Metric magnetic resonance imaging analysis reveals pronounced substantia-innominata atrophy in dementia with Lewy bodies with a psychiatric onset.

BackgroundDementia with Lewy bodies (DLB) is a type of dementia often diagnosed in older patients. Since its initial symptoms range from delirium to psychiatric and cognitive symptoms, the diagnosis is often delayed.ObjectivesIn our study, we evaluated the magnetic resonance imaging (MRI) of patients suffering from DLB in correlation with their initial symptoms taking a new pragmatic approach entailing manual measurements in addition to an automated volumetric analysis of MRI.MethodsA total of 63 patients with diagnosed DLB and valid 3D data sets were retrospectively and blinded evaluated. We assessed atrophy patterns (1) manually for the substantia innominata and (2) via FastSurfer for the most common supratentorial regions. Initial symptoms were categorized by (1) mild cognitive impairment (MCI), (2) psychiatric episodes, and (3) delirium.ResultsManual metric MRI measurements revealed moderate, but significant substantia-innominata (SI) atrophy in patients with a psychiatric onset. FastSurfer analysis revealed no regional volumetric differences between groups.ConclusionThe SI in patients with DLB and a psychiatric-onset is more atrophied than that in patients with initial MCI. Our results suggest potential differences in SI between DLB subtypes at the prodromal stage, which are useful when taking a differential-diagnostic approach. This finding should be confirmed in larger patient cohorts.

P.052 Understanding the influence of APOE-ɛ4 on magnetic resonance imaging-based hippocampal phenotypes in Alzheimer’s disease and Lewy body dementia

Background: The ɛ4-allele of apolipoprotein E (APOE-ɛ4) increases the risk not only for Alzheimer’s disease (AD), but also for Parkinson’s disease dementia and dementia with Lewy bodies (collectively, Lewy body dementia [LBD]). Hippocampal volume is an important neuroimaging biomarker for AD and LBD, although its association with APOE-ɛ4 is inconsistently reported. We investigated the association of APOE-ε4 with hippocampal atrophy quantified using magnetic resonance imaging in AD and LBD. Methods: Electronic databases (PubMed, Embase, PsycINFO, Scopus, Web of Science) were systematically searched for studies published up until December 31st, 2020. Results: Thirty-nine studies (25 cross-sectional, 14 longitudinal) were included. We observed that: (1) APOE-ε4 was associated with greater rate of hippocampal atrophy in AD and those who progressed from mild cognitive impairment to AD, (2) APOE-ε4 carriers showed greater involvement of cornu ammonis-1 hippocampal subfield versus non-carriers in AD, (3) APOE-ɛ4 may influence hippocampal atrophy in dementia with Lewy bodies, although longitudinal investigations are required, and (4) APOE-ε4 associated with earlier rather than very late expression of mediotemporal degeneration and memory-related neurocognitive impairment. Conclusions: The role of APOE-ɛ4 in modulating hippocampal phenotypes may be further clarified through more homogenous, well-powered, pathology-proven studies. Understanding the underlying mechanisms will facilitate development of prevention strategies targeting APOE-ɛ4.

An MRI-based strategy for differentiation of frontotemporal dementia and Alzheimer\u2019s disease

BackgroundThe differential diagnosis of frontotemporal dementia (FTD) and Alzheimer’s disease (AD) is difficult due to the overlaps of clinical symptoms. Structural magnetic resonance imaging (sMRI) presents distinct brain atrophy and potentially helps in their differentiation. In this study, we aim at deriving a novel integrated index by leveraging the volumetric measures in brain regions with significant difference between AD and FTD and developing an MRI-based strategy for the differentiation of FTD and AD.MethodsIn this study, the data were acquired from three different databases, including 47 subjects with FTD, 47 subjects with AD, and 47 normal controls in the NACC database; 50 subjects with AD in the ADNI database; and 50 subjects with FTD in the FTLDNI database. The MR images of all subjects were automatically segmented, and the brain atrophy, including the AD resemblance atrophy index (AD-RAI), was quantified using AccuBrain®. A novel MRI index, named the frontotemporal dementia index (FTDI), was derived as the ratio between the weighted sum of the volumetric indexes in “FTD dominant” structures over that obtained from “AD dominant” structures. The weights and the identification of “FTD/AD dominant” structures were acquired from the statistical analysis of NACC data. The differentiation performance of FTDI was validated using independent data from ADNI and FTLDNI databases.ResultsAD-RAI is a proven imaging biomarker to identify AD and FTD from NC with significantly higher values (p < 0.001 and AUC = 0.88) as we reported before, while no significant difference was found between AD and FTD (p = 0.647). FTDI showed excellent accuracy in identifying FTD from AD (AUC = 0.90; SEN = 89%, SPE = 75% with threshold value = 1.08). The validation using independent data from ADNI and FTLDNI datasets also confirmed the efficacy of FTDI (AUC = 0.93; SEN = 96%, SPE = 70% with threshold value = 1.08).ConclusionsBrain atrophy in AD, FTD, and normal elderly shows distinct patterns. In addition to AD-RAI that is designed to detect abnormal brain atrophy in dementia, a novel index specific to FTD is proposed and validated. By combining AD-RAI and FTDI, an MRI-based decision strategy was further proposed as a promising solution for the differential diagnosis of AD and FTD in clinical practice.

Subcortical atrophy in dementia with Lewy bodies

AbstractBackgroundDementia with Lewy bodies (DLB) is typically associated to less pronounced cortical atrophy than Alzheimer’s disease (AD). However, our clinical experience suggests that DLB patients have a prominent subcortical atrophy, contrasting with overall preserved neocortical and hippocampal regions. Therefore, the objective of the present study was to test the existence of a subcortical atrophy in DLB patients as compared to AD patients and normal controls. We hypothesized that patients with DLB would have larger ventricular volumes than AD patients and controls, at least when considering the ventricular volume relatively to the global cortical volume.MethodWe included 55 DLB patients (30 mild to moderate [d‐DLB], 25 prodromal [pro‐DLB]), and compared their cerebral volumes to those of 51 AD patients (31 mild to moderate [d‐AD], 20 prodromal [pro‐AD]), matched for age, educational level and MMSE scores, and to those of 17 healthy control subjects (CS), matched for age and educational level. Total ventricular volume (TVV) volumes were extracted using freesurfer. We also examine the ratio of the TVV against the total cortical volume (Cortex). We included Total intracranial volume and age as nuisance covariates.ResultWe found that both d‐DLB group(p = 0.003) and pro‐DLB group (p = 0.006) had significantly higher TVV compared to the CS. Compared to the AD patients, TVV was significantly higher in the d‐DLB group vs. the d‐AD group (p = 0.03), though, only at the level of a trend in the pro‐DLB group vs. pro‐AD group (p = 0.055). As for the TVV/Cortex ratio, a significant difference was found for the DLB groups compared to both CS (d‐DLB: p = 0.002; pro‐DLB: p = 0.004) and AD groups (d‐DLB vs. d‐AD: p = 0.03; pro‐DLB vs. pro‐AD: p = 0.04).ConclusionDLB patients have higher ventricular volumes compared to healthy controls and AD patients, reflecting a larger subcortical atrophy. This was more particularly the case when considering the ventricular volume relatively to the global cortical volume, which suggests it could serve as a potential biomarker for the differential diagnosis between DLB and AD patients, even at the prodromal stage.

A cross-sectional and longitudinal study on the protective effect of bilingualism against dementia using brain atrophy and cognitive measures

BackgroundEvidence from previous studies suggests that bilingualism contributes to cognitive reserve because bilinguals manifest the first symptoms of Alzheimer’s disease (AD) up to 5 years later than monolinguals. Other cross-sectional studies demonstrate that bilinguals show greater amounts of brain atrophy and hypometabolism than monolinguals, despite sharing the same diagnosis and suffering from the same symptoms. However, these studies may be biased by possible pre-existing between-group differences.MethodsIn this study, we used global parenchymal measures of atrophy and cognitive tests to investigate the protective effect of bilingualism against dementia cross-sectionally and prospectively, using a sample of bilinguals and monolinguals in the same clinical stage and matched on sociodemographic variables.ResultsOur results suggest that the two groups did not differ in their cognitive status at baseline, but bilinguals had less parenchymal volume than monolinguals, especially in areas related to brain atrophy in dementia. In addition, a longitudinal prospective analysis revealed that monolinguals lost more parenchyma and had more cognitive decline than bilinguals in a mean follow-up period of 7 months.ConclusionThese results provide the first prospective evidence that bilingualism may act as a neuroprotective factor against dementia and could be considered a factor in cognitive reserve.

Cough reflex sensitivity and urge-to-cough deterioration in dementia with Lewy bodies.

Cough, an important respiratory symptom, predominantly involves the brainstem and the urge-to-cough (UTC) is modulated by the cerebral cortex. Lewy body disease is associated with decreased cough reflex sensitivity and central respiratory chemosensitivity. Additionally, the insula, associated with the UTC, shows decreased activation and atrophy in dementia with Lewy bodies (DLB). We investigated the relationships between cognition and cough reflex and the UTC and compared the differences in responses of patients with DLB and other dementia subtypes.We conducted a cross-sectional study within a geriatric ward of a university hospital involving elderly patients diagnosed with Alzheimer's disease (AD), DLB, or non-dementia (controls). The cough reflex sensitivities were estimated based on the lowest concentrations of inhaled citric acid that could induce ≥2 coughs (C2) or ≥5 coughs (C5). Subjects were asked to rate the UTC based on the threshold concentrations (Cu) using the modified Borg scale.C2, C5 and Cu were negatively correlated with cognitive function in female participants but not in males (p<0.01). The cough reflex sensitivities expressed as C2 and C5 were significantly higher in the DLB group than in the AD and control groups (p<0.01 adjusted for gender). The UTC threshold expressed as Cu was also significantly higher in the DLB group, while the UTC log–log slope was less responsive in the DLB group than in the other groups.The cough reflex sensitivity and perceived UTC deteriorated in the DLB group more than in the other groups. This result might be valuable in treating patients with DLB.

The combined effect of amyloid-β and tau biomarkers on brain atrophy in dementia with Lewy bodies

BackgroundAlzheimer’s disease (AD)-related pathology is frequently found in patients with dementia with Lewy bodies (DLB). However, it is unknown how amyloid-β and tau-related pathologies influence neurodegeneration in DLB. Understanding the mechanisms underlying brain atrophy in DLB can improve our knowledge about disease progression, differential diagnosis, drug development and testing of anti-amyloid and anti-tau therapies in DLB. ObjectivesWe aimed at investigating the combined effect of CSF amyloid-β42, phosphorylated tau and total tau on regional brain atrophy in DLB in the European DLB (E-DLB) cohort. Methods86 probable DLB patients from the E-DLB cohort with CSF and MRI data were included. Random forest was used to analyze the association of CSF biomarkers (predictors) with visual rating scales for medial temporal lobe atrophy (MTA), posterior atrophy (PA) and global cortical atrophy scale-frontal subscale (GCA-F) (outcomes), including age, sex, education and disease duration as extra predictors. ResultsDLB patients with abnormal MTA scores had abnormal CSF Aβ42, shorter disease duration and older age. DLB patients with abnormal PA scores had abnormal levels of CSF Aβ42 and p-tau, older age, lower education and shorter disease duration. Abnormal GCA-F scores were associated with lower education, male sex, and older age, but not with any AD-related CSF biomarker. ConclusionsThis study shows preliminary data on the potential combined effect of amyloid-β and tau-related pathologies on the integrity of posterior brain cortices in DLB patients, whereas only amyloid-β seems to be related to MTA. Future availability of α-synuclein biomarkers will help us to understand the effect of α-synuclein and AD-related pathologies on brain integrity in DLB.

Human myeloperoxidase (hMPO) is expressed in neurons in the substantia nigra in Parkinson's disease and in the hMPO-α-synuclein-A53T mouse model, correlating with increased nitration and aggregation of α-synuclein and exacerbation of motor impairment

α-Synuclein (αSyn) is central to the neuropathology of Parkinson's disease (PD) due to its propensity for misfolding and aggregation into neurotoxic oligomers. Nitration/oxidation of αSyn leads to dityrosine crosslinking and aggregation. Myeloperoxidase (MPO) is an oxidant-generating enzyme implicated in neurodegenerative diseases. In the present work we have examined the impact of MPO in PD through analysis of postmortem PD brain and in a novel animal model in which we crossed a transgenic mouse expressing the human MPO (hMPO) gene to a mouse expressing human αSyn-A53T mutant (A53T) (hMPO-A53T). Surprisingly, our results show that in PD substantia nigra, the hMPO gene is expressed in neurons containing aggregates of nitrated αSyn as well as MPO-generated HOCl-modified epitopes. In our hMPO-A53T mouse model, we also saw hMPO expression in neurons but not mouse MPO. In the mouse model, hMPO was expressed in neurons colocalizing with nitrated αSyn, carbamylated lysine, nitrotyrosine, as well as HOCl-modified epitopes/proteins. RNAscope in situ hybridization confirmed hMPO mRNA expression in neurons. Interestingly, the hMPO protein expressed in hMPO-A53T brain is primarily the precursor proMPO, which enters the secretory pathway potentially resulting in interneuronal transmission of MPO and oxidative species. Importantly, the hMPO-A53T mouse model, when compared to the A53T model, exhibited significant exacerbation of motor impairment on rotating rods, balance beams, and wire hang tests. Further, hMPO expression in the A53T model resulted in earlier onset of end stage paralysis. Interestingly, there was a high concentration of αSyn aggregates in the stratum lacunosum moleculare of hippocampal CA2 region, which has been associated in humans with accumulation of αSyn pathology and neural atrophy in dementia with Lewy bodies. This accumulation of αSyn aggregates in CA2 was associated with markers of endoplasmic reticulum (ER) stress and the unfolded protein response with expression of activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), MPO, and cleaved caspase-3. Together these findings suggest that MPO plays an important role in nitrative and oxidative damage that contributes to αSyn pathology in synucleinopathies.

A signature pattern of cortical atrophy in dementia with Lewy bodies: A study on 333 patients from the European DLB consortium

IntroductionWe explored regional brain atrophy patterns and their clinical correlates in dementia with Lewy bodies (DLB). MethodsIn this multicentre study, we included a total of 333 patients with DLB, 352 patients with Alzheimer's disease (AD), and 233 normal controls and used medial temporal lobe atrophy, posterior atrophy, and frontal atrophy (GCA-F) visual rating scales. Patients were classified according to four atrophy patterns. ResultsPatients with DLB had higher scores on all the three atrophy scales than normal controls but had less medial temporal lobe atrophy than those with AD (all P values < .001). A signature hippocampal-sparing pattern of regional atrophy was observed in DLB. The magnetic resonance imaging measures showed 65% ability to discriminate between DLB and AD and marginally contributed to the discrimination over and above the core clinical features. DiscussionThe most common pattern of atrophy of DLB was hippocampal-sparing. Future studies should explore whether comorbid AD pathology underlies the atrophy patterns seen in DLB.

Beta amyloid deposition maps onto hippocampal and subiculum atrophy in dementia with Lewy bodies.

Although dementia with Lewy bodies (DLB) is a synucleinopathy, it is frequently accompanied by beta amyloid (Aβ) accumulation. Elucidating the relationships of Aβ with gray matter atrophy in DLB may yield insights regarding the contributions of comorbid Alzheimer's disease to its disease progression. Twenty healthy controls and 25 DLB subjects underwent clinical assessment, [18F]-Florbetapir, and 3T magnetic resonance imaging. FreeSurfer was used to estimate cortical thickness and subcortical volumes, and PetSurfer was used to quantify [18F]-Florbetapir standardized uptake value ratio. Principal component analysis was used to identify the dominant Aβ component for correlations with regional cortical thickness, hippocampal subfields, and subcortical structures. Relative to healthy controls, the DLB group demonstrated increased Aβ in widespread regions encompassing the frontal and temporoparietal cortices, whereas cortical thinning was restricted to the temporal lobe. Among DLB subjects, the Aβ component was significantly associated with more severe hippocampal and subiculum atrophy. These findings may reflect an early process of superimposed AD-like atrophy in DLB, thereby conferring support for the therapeutic potential of anti-Aβ interventions in people with DLB.

Gray matter atrophy in dementia with Lewy bodies with and without concomitant Alzheimer's disease pathology.

We aimed to study if patients with dementia with Lewy bodies (DLB) who have concomitant Alzheimer's disease (AD) pathology (detected antemortem by cerebrospinal fluid [CSF] biomarkers) have additional loss of gray matter volume. Ninety-eight DLB patients were divided into a "pure DLB" (DLB/AD-, n= 62) and a "mixed DLB" group (DLB/AD+, n= 36) and matched for age and symptom duration to 84 AD patients and 75 controls. We compared visual atrophy ratings, and in a subset, we analyzed cortical thickness and subcortical gray matter volumes. DLB/AD+ patients had more pronounced medial temporal lobe atrophy (MTA) compared to DLB/AD- (mean [total] MTA score 2.5 vs. 1.3, p= 0.02). Global and parietal atrophy scores were comparable between the 3 dementia groups and differed from controls. MTA score was associated with CSF Aβ-42, while posterior cortical and global atrophy scores were associated with CSF tau. Cortical thinning was found in DLB/AD-, DLB/AD+, and AD compared to controls. Concomitant AD pathology seems to cause additional (hippocampal) atrophy in DLB, and this may contribute to a more devastating disease course in DLB/AD+ patients.

THE INFLUENCE OF CONCOMITANT ALZHEIMER PATHOLOGY ON ATROPHY IN DEMENTIA WITH LEWY BODIES (DLB): A COMPARATIVE MRI STUDY

THE INFLUENCE OF CONCOMITANT ALZHEIMER PATHOLOGY ON ATROPHY IN DEMENTIA WITH LEWY BODIES (DLB): A COMPARATIVE MRI STUDY

Cingulate island sign on FDG-PET is associated with medial temporal lobe atrophy in dementia with Lewy bodies.

The cingulate island sign (CIS), which refers to sparing of the posterior cingulate relative to the precuneus and cuneus, has been proposed as an FDG-PET imaging feature of dementia with Lewy bodies (DLB). The sign is reportedly associated with Alzheimer's disease (AD) type neurofibrillary tangle (NFT) pathology in autopsy cases. To confirm this relationship using neuroimaging modalities in vivo, we investigated associations between CIS and the medial temporal lobe (MTL) atrophy in DLB. Twenty-four patients each of DLB and AD underwent both (18)F-FDG-PET and MRI with voxel-based morphometry. Dopamine transporter (DAT) density was also measured by DAT-SPECT in all those with DLB and in five with AD. The accumulation of FDG in the posterior cingulate ROI was divided by that in the precuneus plus cuneus ROI to derive the CIS ratio from the FDG-PET images. Values for cognitive function of Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Ray Auditory Verbal Learning Test (RAVLT) and scores for the core-feature triad of fluctuation, hallucination and parkinsonism were also statistically analyzed. The CIS ratio was higher in DLB than in AD (p<0.001). The degree of MTL atrophy was lower in DLB than in AD (p<0.001). The CIS ratio and the degree of MTL atrophy were inversely correlated with DLB (p<0.001) and with AD (p<0.05). The CIS ratio did not significantly correlate with DAT density in DLB or with MMSE, FAB, fluctuation score and parkinsonism score. However, the CIS ratio significantly correlated with RAVLT and hallucination scores (both, p<0.05). The CIS on FDG-PET in DLB was associated with MTL atrophy but not with striatal DAT density, suggesting that the CIS is a useful neuroimaging biomarker to evaluate coexisting AD-type NFT pathologyin vivo. The CIS was also associated with memory impairment and visual hallucination in DLB.

Progressive cortical thinning and subcortical atrophy in dementia with Lewy bodies and Alzheimer's disease

Patterns of progressive cortical thinning in dementia with Lewy bodies (DLB) remain poorly understood. We examined spatiotemporal patterns of cortical thinning and subcortical atrophy over 12 months in DLB (n = 13), compared with Alzheimer's disease (AD) (n = 23) and healthy control subjects (HC) (n = 33). Rates of temporal thinning in DLB were relatively preserved compared with AD. Volumetric analyses subcortical changes revealed that the AD group demonstrated significantly increased hippocampal atrophy (−5.8%) relative to the HC (−1.7%; p < 0.001) and DLB groups (−2.5%, p = 0.006). Significant lateral ventricular expansion was also observed in AD (8.9%) compared with HC (4.3%; p < 0.001) and DLB (4.7%; p = 0.008) at trend level. There was no significant difference in subcortical atrophy and ventricular expansion between DLB and HC. In the DLB group, increased rates of cortical thinning in the frontal and parietal regions were significantly correlated with decline in global cognition (Mini-Mental State Examination) and motor deterioration (Unified Parkinson's Disease Rating Scale 3), respectively. Overall, AD and DLB are characterized by different spatiotemporal patterns of cortical thinning over time. Our findings warrant further consideration of longitudinal cortical thinning as a potential imaging marker to differentiate DLB from AD.

REM Sleep Behavior Disorder Is Associated with Reduced Alzheimer's Pathology, Hippocampal and Parietotemporal Atrophy in Dementia with Lewy Bodies (S44.006)

REM Sleep Behavior Disorder Is Associated with Reduced Alzheimer's Pathology, Hippocampal and Parietotemporal Atrophy in Dementia with Lewy Bodies (S44.006)

Patterns of gray matter atrophy in dementia with Lewy bodies: a voxel-based morphometry study

Dementia with Lewy bodies (DLB) is a common form of dementia characterized by visual hallucinations, cognitive fluctuation and parkinsonism. We aimed to compare the patterns of gray matter atrophy in DLB with those in Alzheimer's disease (AD) and normal aging, and to investigate the relationship between atrophy and cognitive measures. We used voxel-based morphometry (VBM) to investigate gray matter (GM) loss in DLB (n = 35; mean age = 78.4; MMSE = 20.3), AD (n = 36; mean age = 78.3; MMSE = 19.5) and similar aged controls (n = 35; mean age = 76.7; MMSE = 29.1). T1 weighted MRI scans were acquired at 3 Tesla from all subjects and analyzed using VBM-DARTEL in SPM8. Cognitive function was assessed using the Cambridge Cognitive Examination (CAMCOG). We found reduced gray matter in temporal, parietal, occipital, and subcortical structures in DLB when compared to normal controls. The degree of atrophy was less than that observed in AD. There was significantly more medial temporal lobe atrophy in the AD group when compared with DLB. We did not find a correlation between total CAMCOG score and atrophy, but the CAMCOG memory subscale score correlated with temporal lobe atrophy in both the DLB and combined DLB/AD group. DLB is associated with less gray matter atrophy and relative preservation of the medial temporal lobe when compared to AD. Degree of medial temporal atrophy may be a useful imaging biomarker and our results provide support for its inclusion in the revised consensus criteria for DLB.