Senjem, Matthew L

ABSTRACT Background The clinical course of dementia with Lewy bodies patients is heterogeneous. The ability to more accurately prognosticate survival is important. Objective The objective of this study was to investigate hippocampal volume as a predictor of survival in dementia with Lewy bodies patients. Methods Survival analysis for time from onset of cognitive symptoms to death was carried out using Cox proportional hazards models. Given their age and total intracranial volume, patients were dichotomized into low/medium (0%‐66.7%) and high (66. 7%‐100%) hippocampal volume categories. The models using these categories to predict survival were adjusted for field strength, APOE ε4 status, and estimated onset age of cognitive problems. Results We investigated 167 consecutive patients with dementia with Lewy bodies. The median age at MRI was 72 years (interquartile range 67‐76), and 80% were male. The median time from estimated first cognitive symptom to death was 7.4 years (interquartile range:5.7‐10.2). Lower hippocampal volumes were significantly associated with higher risk of death (hazard ratio 1.28; 95% confidence interval 1.04‐1.58; P = .024). The predicted median survival for participants with onset of cognitive symptoms at age 68 was 10.63 years (95% confidence interval 8.66‐14.54) for APOE ε4 negative, high hippocampal volume participants; 8.89 years (95% confidence interval 7.56‐12.36) for APOE ε4 positive, high hippocampal volume participants; 8.10 years (95% confidence interval 7.34‐11.08) for APOE ε4 negative, low/medium hippocampal volume participants; and 7.38 (95% confidence interval 6.74‐9.29) years for APOE ε4 positive, low/medium hippocampal volume participants. Conclusions Among patients with clinically diagnosed dementia with Lewy bodies, those with neuroimaging evidence of hippocampal atrophy have shorter survival times. © 2016 International Parkinson and Movement Disorder Society

Background: Different clinical syndromes can arise from Alzheimer’s disease (AD) neuropathology, including dementia of the Alzheimer’s type (DAT), logopenic primary progressive aphasia (lvPPA), and posterior cortical atrophy (PCA). Objective: To assess similarities and differences in patterns of white matter tract degeneration across these syndromic variants of AD. Methods: Sixty-four subjects (22 DAT, 24 lvPPA, and 18 PCA) that had diffusion tensor imaging and showed amyloid-β deposition on PET were assessed in this case-control study. A whole-brain voxel-based analysis was performed to assess differences in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity across groups. Results: All three groups showed overlapping diffusion abnormalities in a network of tracts, including fornix, corpus callosum, posterior thalamic radiations, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and uncinate fasciculus. Subtle regional differences were also observed across groups, with DAT particularly associated with degeneration of fornix and cingulum, lvPPA with left inferior fronto-occipital fasciculus and uncinate fasciculus, and PCA with posterior thalamic radiations, superior longitudinal fasciculus, posterior cingulate, and splenium of the corpus callosum. Conclusion: These findings show that while each AD phenotype is associated with degeneration of a specific structural network of white matter tracts, striking spatial overlap exists among the three network patterns that may be related to AD pathology.

AbstractIntroductionThe objective of our study was to investigate cross‐sectional associations of atrial fibrillation with neuroimaging measures of cerebrovascular disease and Alzheimer's disease and their interactions with mild cognitive impairment (MCI).MethodsMagnetic resonance imaging scans of individuals from a population‐based study were analyzed for infarctions, total gray matter, and hippocampal and white matter hyperintensity volumes. A subsample underwent positron emission tomography imaging.ResultsAtrial fibrillation was associated with infarctions and lower total gray matter volume. Compared with subjects with no atrial fibrillation and no infarction, the odds ratio (95% confidence intervals) for MCI was 2.99 (1.57–5.70; P = .001) among participants with atrial fibrillation and infarction, 0.90 (0.45–1.80; P = .77) for atrial fibrillation and no infarction, and 1.50 (0.96–2.34; P = .08) for no atrial fibrillation and any infarction.DiscussionParticipants with both atrial fibrillation and infarction are more likely to have MCI than participants with either infarction or atrial fibrillation alone.

ObjectiveThe aim of this study was to determine whether the frequency of TAR DNA‐binding protein 43 (TDP‐43) deposition in Alzheimer's disease (AD) differs across pathologically defined AD subtypes (hippocampal sparing [HpSp]; typical and limbic) and further examine the relationship between TDP‐43, pathological subtype, and clinical features in AD.MethodsWe identified all cases with pathologically confirmed AD (NIA‐Reagan intermediate‐high probability, Braak stage IV–VI) independent of cognitive status (n = 188). Neurofibrillary tangle counts were performed using thioflavin‐S microscopy in hippocampus and three neocortical regions, and all cases were subtyped: HpSp AD pathology (n = 19); typical AD pathology (n = 136); and limbic AD pathology (n = 33). TDP‐43 immunoreactivity was performed in multiple brain regions to assess for the presence of TDP‐43 and TDP‐43 stage. All cases were clinically subclassified at presentation as amnestic AD dementia versus atypical AD dementia. Statistical analysis was performed using linear and penalized logistic regression to assess associations with pathological subtype, and the effects of TDP‐43, accounting for possible interactions between pathological subtype and TDP‐43.ResultsTDP‐43 deposition was frequent in typical (59%) and limbic AD pathologies (67%), but not HpSp AD pathology (21%; p = 0.003). The observed associations of TDP‐43 with greater memory loss, naming and functional decline, and smaller hippocampal volumes, closest to death, did not differ across AD pathological subtype. Clinical presentation was associated with pathological subtype (p = 0.01), but not TDP‐43 (p = 0.69).InterpretationAlthough the frequency of TDP‐43 deposition in AD varies by pathological subtype, the observed effects of TDP‐43 on clinical/magnetic resonance imaging features are consistent across pathological subtypes. Clinical presentation in AD is driven by pathological subtype, not by TDP‐43. Ann Neurol 2015;78:Ann Neurol 2015;78:679–696