Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort

Kramberger, Milica G.; Auestad, Bjørn; García-Ptacek, Sara; Abdelnour, Carla; Olmo, Josep Garre; Walker, Zuzana; Lemstra, Afina W.; Londos, Elisabet; Blanc‬, ‪Frederic; Bonanni, Laura; McKeith, Ian G.; Winblad, Bengt; Jong, Frank Jan de; Nobili, Flavio; Stefanova, Elka; Petrova, M. A.; Falup‐Pecurariu, Cristian; Rektorová, Irena; Bostantjopoulou, Sevasti; Biundo, Roberta; Weintraub, Daniel; Aarsland, Dag

doi:10.3233/jad-161109

Cited by 76 publications

(73 citation statements)

References 27 publications

(24 reference statements)

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“…13 In this framework, a work package was devoted to the retrospective collection of functional imaging studies (FDG PET and DAT SPECT) of probable DLB patients with the aim of creating a repository hosted in the core laboratory at the Genoa center. 13 In this framework, a work package was devoted to the retrospective collection of functional imaging studies (FDG PET and DAT SPECT) of probable DLB patients with the aim of creating a repository hosted in the core laboratory at the Genoa center.…”

Section: Methodsmentioning

confidence: 99%

“…13 Given the retrospective nature of the present study, diagnosis of probable DLB was originally made according to diagnostic criteria for probable DLB as defined by McKeith et al in 2005. 13 Given the retrospective nature of the present study, diagnosis of probable DLB was originally made according to diagnostic criteria for probable DLB as defined by McKeith et al in 2005.…”

Section: Patientsmentioning

confidence: 99%

“…Recruited patients were referred to and assessed at outpatient clinics including memory, movement disorders, geriatric medicine, psychiatric, and neurology clinics as previously described in detail. 13 Given the retrospective nature of the present study, diagnosis of probable DLB was originally made according to diagnostic criteria for probable DLB as defined by McKeith et al in 2005. 14 However, the presence of probable RBD as proposed in the 2017 criteria was considered among the disease core features for patient subgrouping.…”

Section: Patientsmentioning

confidence: 99%

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Metabolic patterns across core features in dementia with lewy bodies

Morbelli

Chincarini

Brendel

et al. 2019

Annals of Neurology

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Objective: To identify brain regions whose metabolic impairment contributes to dementia with Lewy bodies (DLB) clinical core features expression and to assess the influence of severity of global cognitive impairment on the DLB hypometabolic pattern. Methods: Brain fluorodeoxyglucose positron emission tomography and information on core features were available in 171 patients belonging to the imaging repository of the European DLB Consortium. Principal component analysis was applied to identify brain regions relevant to the local data variance. A linear regression model was applied to generate core-feature-specific patterns controlling for the main confounding variables (Mini-Mental State Examination [MMSE], age, education, gender, and center). Regression analysis to the locally normalized intensities was performed to generate an MMSE-sensitive map. Results: Parkinsonism negatively covaried with bilateral parietal, precuneus, and anterior cingulate metabolism; visual hallucinations (VH) with bilateral dorsolateral-frontal cortex, posterior cingulate, and parietal metabolism; and rapid eye movement sleep behavior disorder (RBD) with bilateral parieto-occipital cortex, precuneus, and ventrolateral-frontal View this article online at wileyonlinelibrary.com.

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Section: Methodsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

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Metabolic patterns across core features in dementia with lewy bodies

Morbelli

Chincarini

Brendel

et al. 2019

Annals of Neurology

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“…In the great majority of subjects with both ADD and LBD, this co-existence is recognized only at autopsy [41,[112][113][114][115], currently preventing, except for the minority with clinically-typical DLB, the exclusion or stratification of LBD subjects within ADD clinical trials.The presence of LBD in ADD is clearly of clinical significance. Multiple autopsy-validated studies have indicated that cognitive decline is faster in ADD with any degree of associated LBD [26,[42][43][44][45]. Formerly, it was not apparent whether or not this was primarily driven by dementia with Lewy bodies (DLB) subjects with neuropathologically-severe LBD (mostly neocortical stage diffuse Lewy body disease), as disease duration is reportedly shorter in this group [109,116].…”

mentioning

confidence: 93%

“…If all neuropathological changes found in elderly brains were considered, there would be few if any cases of "pure" ADD. While not all of these aging changes are likely be clinically significant [37], several of the commonly-observed ADD comorbidities have been demonstrated to contribute to cognitive impairment, including Lewy body disease (LBD) [4,23,26,30,[41][42][43][44][45][46][47], hippocampal sclerosis [29,[47][48][49][50][51][52], 13,37,[53][54][55][56][57] and cerebral infarcts [1,10,11,30,35,46,57,58,[58][59][60][61][62][63][64][65][66][67][68][69][70]. Aside from causing increased variability in clinical response, it is possib...…”

mentioning

confidence: 99%

Alzheimer’s Disease Neuropathological Comorbidities Are Common in the Younger-Old

Beach

Malek‐Ahmadi

2020

Preprint

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Clinicopathological studies have demonstrated that Alzheimer's disease dementia (ADD) is often accompanied by clinically undetectable comorbid neurodegenerative and cerebrovascular disease that alter the presence and rate of cognitive decline in aging and ADD. Aside from causing increased variability in clinical response, it is possible that the major ADD comorbidities may not respond to ADD-specific molecular therapeutics. As most reports have focused on comorbidity in the oldest-old, its extent in younger age groups that are more likely to be involved in clinical trials is largely unknown. We conducted a survey of neuropathological comorbidities in sporadic ADD using data from the US National Alzheimer's Coordinating Center. Subject data was restricted to those with dementia and meeting National Institute on Aging-Alzheimer's Association (NIA-AA) intermediate or high AD Neuropathological Change (ADNC) levels, excluding those with known autosomal dominant AD-related mutations. Subjects were divided into age-atdeath categories for analysis: under 60, 60-69, 70-79, 80-89, 90-99 and 100 or over. Confirmatory of earlier reports, ADD histopathology is less severe with advancing age, effectively increasing the relative contribution of comorbidities, most of which rise in prevalence with age. Highly prevalent ADD comorbidities are not restricted to the oldest-old but are common even in early-onset ADD. The percentage of cases with ADD as the sole major neuropathological diagnosis is highest in the under-60 group, where "pure" ADD cases are still in the minority at 44%. After this AD as a sole major pathology in ADD declines to roughly 20% in the 70s and beyond. Comorbidity rates for some pathologies, especially LBD, are high even in subjects in their 60s and 70s, at nearly 60%, but for most others, their prevalence increases with age. TDP-43 pathology affects more than 35% of ADD subjects 80 and over while microscopic infarcts reach this rate a decade later. Gross infarcts rise more slowly and affect fewer subjects but still involve 15-20% of ADD after age 80. White matter rarefaction may be underestimated in the NACC database but is present in almost 70% of centenarians with ADD. Effective clinical trials depend on accurate estimates of required subject numbers, which are dependent on observed effect size and clinical response variability. Comorbidities are likely to affect both, leading to lower probability of clinical trial success. Stratifying ADD clinical trial analyses by presence and types of accompanying comorbidities might identify subgroups with higher effect sizes and greater clinical response rates, but accurate in-vivo diagnostic methods for most comorbidities are still lacking. Neuropathological studies are increasingly demonstrating that Alzheimer's disease dementia (ADD) is most often not the sole brain pathology in those that die and are autopsied, but is very likely to be accompanied by comorbid neurodegenerative and cerebrovascular disease. Comorbidities are likely to alter the presence and rate of ...

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Association of Longitudinal β-Amyloid Accumulation Determined by Positron Emission Tomography With Clinical and Cognitive Decline in Adults With Probable Lewy Body Dementia

et al. 2019

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Key PointsQuestionWhat is the trajectory of β-amyloid accumulation over time, and how is it associated with clinical and cognitive decline among patients with probable dementia with Lewy bodies?FindingsThis cohort study of 175 participants found that the cumulative density of β-amyloid accumulation by time in years followed a sigmoid-shaped form among patients with probable dementia with Lewy bodies as well as among cognitively unimpaired participants who were matched by age, sex, and apolipoprotein e4 status. In dementia with Lewy bodies, both baseline and longitudinal β-amyloid load accumulation were associated with measures of clinical and cognitive decline over time.MeaningThe results of this study suggest that longitudinal β-amyloid accumulation among patients with dementia with Lewy bodies could be used to track the clinical progression of dementia with Lewy bodies and potentially to design clinical trials targeting β-amyloid in dementia with Lewy bodies.

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Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort

Cited by 76 publications

References 27 publications

Metabolic patterns across core features in dementia with lewy bodies

Metabolic patterns across core features in dementia with lewy bodies

Alzheimer’s Disease Neuropathological Comorbidities Are Common in the Younger-Old

Association of Longitudinal β-Amyloid Accumulation Determined by Positron Emission Tomography With Clinical and Cognitive Decline in Adults With Probable Lewy Body Dementia

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