INTRODUCTION: We explored regional brain atrophy patterns and their clinical correlates in dementia with Lewy bodies (DLB). METHODS: In 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. RESULTS: Patients 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. DISCUSSION: The 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.

• Klíčová slova
• Alzheimer's disease, Dementia, Dementia with Lewy bodies, Differential diagnosis, Hippocampal spearing atrophy pattern, Limbic-predominant atrophy pattern, Magnetic resonance imaging, Medial temporal atrophy, Minimal-atrophy pattern, Neuroimaging, Posterior atrophy frontal atrophy, Typical Alzheimer's disease atrophy pattern,
• MeSH
• Alzheimerova nemoc diagnostické zobrazování   patologie   MeSH
• atrofie MeSH
• demence s Lewyho tělísky diagnostické zobrazování   patologie   MeSH
• diferenciální diagnóza MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozková kůra diagnostické zobrazování   patologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• testy pro posouzení mentálních funkcí a demence MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Geografické názvy
• Evropa MeSH

INTRODUCTION: 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). METHODS: 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). RESULTS: 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. DISCUSSION: 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. HIGHLIGHTS: 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.

• Klíčová slova
• atrophy, dementia with Lewy bodies, magnetic resonance imaging, sex differences,
• MeSH
• Alzheimerova nemoc * patologie   MeSH
• atrofie patologie   MeSH
• demence s Lewyho tělísky * diagnostické zobrazování   patologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozková kůra patologie   MeSH
• pohlavní dimorfismus MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND/OBJECTIVE: The aim of this study was to describe the rate and clinical predictors of cognitive decline in dementia with Lewy bodies (DLB), and compare the findings with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) patients. METHODS: Longitudinal scores for the Mini-Mental State Examination (MMSE) in 1,290 patients (835 DLB, 198 PDD, and 257 AD) were available from 18 centers with up to three years longitudinal data. Linear mixed effects analyses with appropriate covariates were used to model MMSE decline over time. Several subgroup analyses were performed, defined by anti-dementia medication use, baseline MMSE score, and DLB core features. RESULTS: The mean annual decline in MMSE score was 2.1 points in DLB, compared to 1.6 in AD (p = 0.07 compared to DLB) and 1.8 in PDD (p = 0.19). Rates of decline were significantly higher in DLB compared to AD and PDD when baseline MMSE score was included as a covariate, and when only those DLB patients with an abnormal dopamine transporter SPECT scan were included. Decline was not predicted by sex, baseline MMSE score, or presence of specific DLB core features. CONCLUSIONS: The average annual decline in MMSE score in DLB is approximately two points. Although in the overall analyses there were no differences in the rate of decline between the three neurodegenerative disorders, there were indications of a more rapid decline in DLB than in AD and PDD. Further studies are needed to understand the predictors and mechanisms of cognitive decline in DLB.

• Klíčová slova
• Dementia with Lewy bodies, international cohort, long-term cognitive decline, multicenter study,
• MeSH
• analýza rozptylu MeSH
• demence s Lewyho tělísky komplikace   diagnóza   MeSH
• kognitivní poruchy diagnóza   etiologie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezinárodní spolupráce MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• záznam o duševním stavu MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

The differential diagnosis of dementia with Lewy bodies (DLB) and sporadic Creutzfeldt-Jakob disease (CJD) may be challenging. Patients with the original diagnosis of possible CJD may occasionally prove to have a pathological diagnosis of DLB, while other cases may fulfill the diagnostic clinical criteria for DLB but subsequent clinical course, cerebrospinal fluid (CSF) and neuropathology findings necessitate diagnostic revision to CJD. We describe a 79-year old patient recently diagnosed with dementia with Lewy bodies (DLB) on the basis of subacute cognitive decline, visual hallucinations and Parkinsonian features, who presented with increasing agitation. Brain neuroimaging with MRI raised the diagnostic suspicion of CJD and subsequent diagnostic work-up with electroencephalography (EEG) and CSF analysis led to the establishment of CJD diagnosis. The present case highlights the clinical utility of novel diagnostic CJD criteria that also incorporate neuroimaging findings in the diagnostic CJD panel.

• Klíčová slova
• Creutzfeldt–Jakob disease, Dementia with Lewy bodies, MRI, Neuroimaging,
• MeSH
• Creutzfeldtova-Jakobova nemoc komplikace   diagnóza   MeSH
• demence s Lewyho tělísky komplikace   diagnóza   MeSH
• difuzní magnetická rezonance MeSH
• elektroencefalografie MeSH
• lidé MeSH
• mozek patologie   patofyziologie   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

We investigated whether cerebrovascular disease contributes to neurodegeneration and clinical phenotype in dementia with Lewy bodies (DLB). Regional cortical thickness and subcortical gray matter volumes were estimated from structural magnetic resonance imaging (MRI) in 165 DLB patients. Cortical and subcortical infarcts were recorded and white matter hyperintensities (WMHs) were assessed. Subcortical only infarcts were more frequent (13.3%) than cortical only infarcts (3.1%) or both subcortical and cortical infarcts (2.4%). Infarcts, irrespective of type, were associated with WMHs. A higher WMH volume was associated with thinner orbitofrontal, retrosplenial, and posterior cingulate cortices, smaller thalamus and pallidum, and larger caudate volume. A higher WMH volume was associated with the presence of visual hallucinations and lower global cognitive performance, and tended to be associated with the absence of probable rapid eye movement sleep behavior disorder. Presence of infarcts was associated with the absence of parkinsonism. We conclude that cerebrovascular disease is associated with gray matter neurodegeneration in patients with probable DLB, which may have implications for the multifactorial treatment of probable DLB.

• Klíčová slova
• Cerebrovascular disease, Dementia with Lewy bodies (DLB), Magnetic resonance imaging, Neurodegeneration, White matter hyperintensities, infarcts,
• MeSH
• bílá hmota diagnostické zobrazování   patologie   MeSH
• cerebrovaskulární poruchy komplikace   MeSH
• degenerace nervu etiologie   MeSH
• demence s Lewyho tělísky diagnostické zobrazování   etiologie   patologie   psychologie   MeSH
• halucinace MeSH
• kognice MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozková kůra krevní zásobení   diagnostické zobrazování   patologie   MeSH
• mozkový infarkt diagnostické zobrazování   patologie   MeSH
• porucha chování v REM spánku etiologie   MeSH
• šedá hmota diagnostické zobrazování   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia after Alzheimer's disease (AD). Although diagnosis may be challenging, there is increasing evidence that the use of biomarkers according to 2017 revised criteria for diagnosis and management of dementia with Lewy bodies can increase diagnostic accuracy. Apart from nuclear medicine techniques, various magnetic resonance imaging (MRI) techniques have been utilized in attempt to enhance diagnostic accuracy. This chapter reviews structural, functional and diffusion MRI studies in DLB cohorts being compared to healthy controls, AD or dementia in Parkinson's disease (PDD). We also included relatively new MRI methods that may have potential to identify early DLB subjects and aim at examining brain iron and neuromelanin.

• Klíčová slova
• Diffusion tensor imaging, Functional, MRI, Neuromelanin, Nigrosome-1, Quantitative susceptibility mapping, Resting state fMRI, Structural, White matter hyperintensities,
• MeSH
• demence s Lewyho tělísky diagnostické zobrazování   patofyziologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Mild cognitive impairment with the core clinical features of dementia with Lewy bodies is recognized as a prodromal stage of dementia with Lewy bodies. Although grey matter atrophy has been demonstrated in prodromal dementia with Lewy bodies, longitudinal rates of atrophy during progression to probable dementia with Lewy bodies are unknown. We investigated the regional patterns of cross-sectional and longitudinal rates of grey matter atrophy in prodromal dementia with Lewy bodies, including those who progressed to probable dementia with Lewy bodies. Patients with mild cognitive impairment with at least one core clinical feature of dementia with Lewy bodies (mean age = 70.5; 95% male), who were enrolled in the Mayo Clinic Alzheimer's Disease Research Center and followed for at least two clinical evaluations and MRI examinations, were included (n = 56). A cognitively unimpaired control group (n = 112) was matched 2:1 to the patients with mild cognitive impairment by age and sex. Patients either remained stable (n = 28) or progressed to probable dementia with Lewy bodies (n = 28) during a similar follow-up period and pathologic confirmation was available in a subset of cases (n = 18). Cross-sectional and longitudinal rates of grey matter atrophy were assessed using voxel-based and atlas-based region of interest analyses. At baseline, prodromal dementia with Lewy bodies was characterized by atrophy in the nucleus basalis of Meynert both in those who remained stable and those who progressed to probable dementia with Lewy bodies (P < 0.05 false discovery rate corrected). Increase in longitudinal grey matter atrophy rates were widespread, with greatest rates of atrophy observed in the enthorhinal and parahippocampal cortices, temporoparietal association cortices, thalamus and the basal ganglia, in mild cognitive impairment patients who progressed to probable dementia with Lewy bodies at follow-up (P < 0.05 false discovery rate corrected). Rates of inferior temporal atrophy were associated with greater rates of worsening on the clinical dementia rating-sum of boxes. Seventeen of the 18 (94%) autopsied cases had Lewy body disease. Results show that atrophy in the nucleus basalis of Meynert is a feature of prodromal dementia with Lewy bodies regardless of proximity to progression to probable dementia with Lewy bodies. Longitudinally, grey matter atrophy progresses in regions with significant cholinergic innervation, in alignment with clinical disease progression, with widespread and accelerated rates of atrophy in patients who progress to probable dementia with Lewy bodies. Given the prominent neurodegeneration in the cholinergic system, patients with prodromal dementia with Lewy bodies may be candidates for cholinesterase inhibitor treatment.

• Klíčová slova
• MRI, atrophy, dementia with Lewy bodies, mild cognitive impairment, prodromal DLB,
• Publikační typ
• časopisecké články MeSH

NPC1 encodes a lysosomal protein involved in cholesterol transport. Biallelic mutations in this gene may lead to Niemann-Pick disease type C (NPC), a lysosomal storage disorder. The role of NPC1 in alpha synucleinopathies is still unclear, as different genetic, clinical, and pathological studies have reported contradictory results. This study aimed to evaluate the association of NPC1 variants with the synucleinopathies Parkinson's disease (PD), dementia with Lewy bodies (DLB), and rapid eye movement-sleep behavior disorder (RBD). We analyzed common and rare variants from 3 cohorts of European descent: 1084 RBD cases and 2945 controls, 2852 PD cases and 1686 controls, and 2610 DLB cases and 1920 controls. Logistic regression models were used to assess common variants while optimal sequence Kernel association tests were used to assess rare variants, both adjusted for sex, age, and principal components. No variants were associated with any of the synucleinopathies, supporting that common and rare NPC1 variants do not play an important role in alpha synucleinopathies.

• Klíčová slova
• Association study, Dementia with Lewy bodies, NPC1, Niemann-Pick disease type C, Parkinson’s disease, REM-sleep behavior disorder,
• MeSH
• demence s Lewyho tělísky * genetika   MeSH
• lidé MeSH
• Parkinsonova nemoc * genetika   MeSH
• porucha chování v REM spánku * genetika   MeSH
• protein NPC1 MeSH
• spánek MeSH
• synukleinopatie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• NPC1 protein, human MeSH Prohlížeč
• protein NPC1 MeSH

Dementia with Lewy bodies (DLB) is characterized by preserved whole brain and medial temporal lobe volumes compared with Alzheimer's disease dementia (AD) on magnetic resonance imaging. However, frequently coexistent AD-type pathology may influence the pattern of regional brain atrophy rates in DLB patients. We investigated the pattern and magnitude of the atrophy rates from 2 serial MRIs in autopsy-confirmed DLB patients (n = 20) and mixed DLB/AD patients (n = 22), compared with AD (n = 30) and elderly nondemented control subjects (n = 15), followed antemortem. DLB patients without significant AD-type pathology were characterized by lower global and regional rates of atrophy, similar to control subjects. The mixed DLB/AD patients displayed greater atrophy rates in the whole brain, temporoparietal cortices, hippocampus and amygdala, and ventricle expansion, similar to AD patients. In the DLB and DLB/AD patients, the atrophy rates correlated with Braak neurofibrillary tangle stage, cognitive decline, and progression of motor symptoms. Global and regional atrophy rates are associated with AD-type pathology in DLB, and these rates can be used as biomarkers of AD progression in patients with LB pathology.

• Klíčová slova
• Alzheimer's disease, Atrophy rate, Autopsy-confirmed dementia with Lewy bodies, Braak neurofibrillary tangle stage, Sample size estimate, Serial MRI,
• MeSH
• Alzheimerova nemoc diagnóza   patologie   MeSH
• amygdala patologie   MeSH
• atrofie MeSH
• biologické markery MeSH
• demence s Lewyho tělísky patologie   psychologie   MeSH
• hipokampus patologie   MeSH
• kognice MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   MeSH
• neurofibrilární klubka patologie   MeSH
• pitva MeSH
• progrese nemoci MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spánkový lalok patologie   MeSH
• temenní lalok patologie   MeSH
• velikost orgánu MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• biologické markery MeSH

Many patients with dementia with Lewy bodies (DLB) have overlapping Alzheimer's disease (AD)-related pathology, which may contribute to white matter (WM) diffusivity alterations on diffusion tensor imaging (DTI). Consecutive patients with DLB (n = 30), age- and sex-matched AD patients (n = 30), and cognitively normal controls (n = 60) were recruited. All subjects underwent DTI, 18F 2-fluoro-deoxy-d-glucose, and (11)C Pittsburgh compound B positron emission tomography scans. DLB patients had reduced fractional anisotropy (FA) in the parietooccipital WM but not elsewhere compared with cognitively normal controls, and elevated FA in parahippocampal WM compared with AD patients, which persisted after controlling for β-amyloid load in DLB. The pattern of WM FA alterations on DTI was consistent with the more diffuse posterior parietal and occipital glucose hypometabolism of 2-fluoro-deoxy-d-glucose positron emission tomography in the cortex. DLB is characterized by a loss of parietooccipital WM integrity, independent of concomitant AD-related β-amyloid load. Cortical glucose hypometabolism accompanies WM FA alterations with a concordant pattern of gray and WM involvement in the parietooccipital lobes in DLB.

• Klíčová slova
• Amyloid-beta load, Cortical hypometabolism, Dementia with Lewy bodies, Diffusion tensor imaging, Voxel-based analysis, White matter integrity,
• MeSH
• amyloidní beta-protein metabolismus   MeSH
• anizotropie MeSH
• bílá hmota patologie   MeSH
• demence s Lewyho tělísky diagnostické zobrazování   metabolismus   patologie   MeSH
• glukosa metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pozitronová emisní tomografie MeSH
• senioři MeSH
• týlní lalok metabolismus   MeSH
• zobrazování difuzních tenzorů metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• amyloidní beta-protein MeSH
• glukosa MeSH