Dataset Information

Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies.

ABSTRACT: 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.

SUBMITTER: Ferreira D

PROVIDER: S-EPMC8338792 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies.

Ferreira Daniel D Nedelska Zuzana Z Graff-Radford Jonathan J Przybelski Scott A SA Lesnick Timothy G TG Schwarz Christopher G CG Botha Hugo H Senjem Matthew L ML Fields Julie A JA Knopman David S DS Savica Rodolfo R Ferman Tanis J TJ Graff-Radford Neill R NR Lowe Val J VJ Jack Clifford R CR Petersen Ronald C RC Lemstra Afina W AW van de Beek Marleen M Barkhof Frederik F Blanc Frederic F Loureiro de Sousa Paulo P Philippi Nathalie N Cretin Benjamin B Demuynck Catherine C Hort Jakub J Oppedal Ketil K Boeve Bradley F BF Aarsland Dag D Westman Eric E Kantarci Kejal K

Neurobiology of aging 20210514

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 ...[more]

PMID: 34130107

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Project description: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.

Project description:ImportanceEarly-onset dementia, presenting in individuals younger than 65 years, is a diagnosis with significant social and financial implications. The early-onset form of dementia with Lewy bodies (DLB) is poorly understood.ObjectiveTo investigate clinical features that distinguish early-onset DLB (onset and diagnosis at age <65 years) from late-onset DLB (onset at age ≥65 years) and from early-onset Alzheimer disease (AD) dementia.Design, setting, and participantsThis is a retrospective case-control study on patients with pathologically confirmed DLB or AD enrolled in the National Alzheimer's Coordinating Center database from January 2005 to July 2017. The National Alzheimer's Coordinating Center Uniform Data Set comprised deidentified data collected by Alzheimer disease centers in the United States. Of patients fulfilling criteria for all-cause dementia at enrollment (n = 1152), those who at post mortem received a pathological diagnosis of either AD (n = 848) or Lewy body disease (n = 218) were selected. Excluding 52 patients owing to missing data and 12 diagnosed with Parkinson disease dementia, remaining patients were classified by age of symptom onset into early-onset AD, early-onset DLB, and late-onset DLB subgroups. Data were analyzed from June to December 2018 and from November to December 2021.ExposuresDemographics, cognitive, behavioral, and motor features recorded at first clinic visit and neuropathological characteristics at autopsy were analyzed by disease subgroup.Main outcomes and measuresConcordance between initial etiologic diagnosis of dementia and final pathological diagnosis was assessed, as was time to death.ResultsA total of 542 individuals were categorized as having early-onset AD (n = 363; mean [SD] age, 53.0 [5.8] years; 208 [57.3%] male), early-onset DLB (n = 32; mean [SD] age, 57.9 [3.2] years; 23 [71.9%] male), and late-onset DLB (n = 147; mean [SD] age, 73.5 [5.5] years; 103 [70.1%] male). Early-onset DLB was clinically misdiagnosed in 16 individuals (50%). Features that predicted a diagnosis of early-onset DLB over early-onset AD included visual hallucinations (15 [46.9%] vs 42 [11.6%]), slowness (23 [71.9%] vs 95 [26.2%]), apathy (23 [71.9%] vs 189 [52.1%]), and motor deterioration that preceded cognitive and behavioral symptoms (7 [21.9%] vs 6 [1.7%]). Late-onset DLB had more amnestic features, but this was accounted for by a higher proportion of neocortical neuritic plaques and diffuse plaques (frequent in 79 [53.7%] vs 8 [25%]) than seen in early-onset DLB.Conclusions and relevanceThis study found that early-onset DLB has clinical features that distinguish it from early-onset AD, whereas features of late-onset DLB are associated with a higher burden of AD copathology.

Project description:The clinical delineation of dementia with Lewy bodies (DLB) from Alzheimer disease (AD) remains unclear.To compare neuropsychological profiles in DLB and AD among Caribbean Hispanic family members and participants in a population-based epidemiologic sample using extended neuropsychological test batteries and to explore whether these differences were related to heritable factors.Cross-sectional study.Clinics in northern Manhattan (New York City), the Dominican Republic, and Puerto Rico.We compared measures of memory, orientation, language, and executive and visuospatial functioning between patients with DLB vs AD in 2 Caribbean Hispanic cohorts, including a family sample (89 patients with DLB and 118 patients with AD) and an epidemiologic sample (70 patients with DLB and 157 patients with AD). Patients with DLB in the family sample were further categorized as patients having at least 2 family members with DLB or as patients having 1 family member with DLB.To determine whether observed differences in cognitive profiles were driven by heritable factors, we repeated analyses in the epidemiologic sample after excluding familial cases. We applied general linear models adjusted for age, sex, educational level, disease duration, and apolipoprotein E epsilon4 (OMIM 104310) genotype.Patients with DLB in both samples were more severely impaired in orientation, visuoconstruction, and nonverbal reasoning after controlling for potential confounders. Patients having at least 2 family members with DLB had the most severe impairment in memory, followed by patients having 1 family member with DLB, and then by patients with AD. After excluding familial AD and DLB cases in the epidemiologic sample, the differences between the groups persisted but were attenuated.Compared with patients having AD, patients having DLB are more severely impaired in various cognitive domains, particularly orientation and visuospatial functioning. The difference seems stronger in familial DLB than in sporadic DLB. Whether this divergence in cognitive functions is caused by gene-gene or gene-environmental interactions remains unclear.

Dataset Information

Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies.

Publications

Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies.

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