Bayram, Ece

Objective Age of symptom onset is highly variable in familial frontotemporal lobar degeneration (f‐FTLD). Accurate prediction of onset would inform clinical management and trial enrollment. Prior studies indicate that individualized maps of brain atrophy can predict conversion to dementia in f‐FTLD. We used a Bayesian linear mixed‐effect (BLME) prediction method for identifying accelerated brain volume loss to predict conversion to dementia. Methods Participants included 234 asymptomatic or prodromal carriers of C9orf72 , GRN , or MAPT mutations (including 21 dementia converters) with ≥3 longitudinal magnetic resonance imaging (MRI) T1‐weighted scans. The BLME models established individual voxel‐wise gray matter trajectories using the first 2 scans. Person‐specific clusters of accelerated volume loss were estimated in subsequent scans and tested as predictors of dementia conversion compared with other approaches in time‐varying Cox proportional hazard models covarying for age. Receiver‐operating characteristic (ROC) curves estimated utility of cluster volume in discriminating which participants converted to dementia within 24 months. Results The BLME cluster volume predicted conversion to dementia in f‐FTLD mutation carriers overall and separately in C9orf72 , GRN , and MAPT , with comparable hazard ratios observed for atrophy W‐maps and regional volumes. Within a 24‐month timeframe, BLME cluster volume discriminated dementia converters from non‐converters with larger areas under the curve (AUCs) than other approaches. Interpretation Bayesian‐modeled individualized atrophy scores predict dementia progression among asymptomatic f‐FTLD mutation carriers and may have increased utility compared with other structural imaging methods when studying individuals over shorter timeframes that align with clinical trial design. ANN NEUROL 20269999:n/a–n/a

AbstractIntroductionClinicopathological correlations differ by sex in Lewy body dementia (LBD). However, previous studies have focused on pathological staging systems that place less emphasis on regional pathologies.MethodsWe included 357 people (131 female, 226 male) with a high likelihood of LBD based on pathology from the Brain Bank for Neurodegenerative (Jacksonville, FL). Sex differences for regional Lewy body, senile plaque, and neurofibrillary tangle counts and their associations with clinical LBD diagnosis were assessed.ResultsFemales were less likely to have a clinical LBD diagnosis; they had more Lewy bodies, neurofibrillary tangles, and senile plaques in various regions than males (all p’s < 0.05). A higher likelihood of clinical LBD diagnosis was associated with more middle frontal, cingulate, and entorhinal Lewy body pathology, and more so for males than for females (all p’s < 0.045).DiscussionSex differences for clinicopathological correlations in LBD also occur at the regional pathology level. Females have a higher frequency of clinical misdiagnosis than males.Highlights Females have a higher risk of clinical underdiagnosis for Lewy body dementia (LBD) than males. Regional pathology counts differ by sex for people with a high likelihood of LBD. Regional pathology association with clinical LBD diagnosis differs by sex. Regional Lewy body counts have a stronger association with LBD phenotype for males.

Abstract BACKGROUND We sought to characterize the cognitive profile among individuals with mild cognitive impairment with Lewy bodies (MCI‐LB) to help guide future clinical criteria. METHODS Systematic review and meta‐analysis included MCI‐LB studies with cognitive data from PubMed, Embase, Web of Science, and PsycINFO (January 1990 to March 2023). MCI‐LB scores were compared to controls, MCI due to Alzheimer's disease (MCI‐AD), and dementia with Lewy bodies (DLB) groups with random‐effects models. RESULTS We included 26 studies and 2823 participants. Across all domains, the MCI‐LB group performed worse than controls and better than DLB. Compared to MCI‐AD, the MCI‐LB group performed worse in attention/processing speed ( g = –0.24, 95% confidence interval [CI]: –0.35, –0.12), attention/executive ( g = –0.42, 95% CI: –0.56, –0.28); better in verbal immediate recall ( g = 0.37; 95% CI: 0.15, 0.59) and delayed memory ( g = 0.40; 95% CI: 0.22, 0.58). DISCUSSION The cognitive profiles in MCI‐LB and MCI‐AD are consistent with established profiles in DLB and AD. Neuropsychological assessment may be helpful in differential diagnosis, even in early disease states. Highlights We performed a systematic review and meta‐analysis for cognition in mild cognitive impairment with Lewy bodies (MCI‐LB). Compared to MCI due to Alzheimer's disease (MCI‐AD), MCI‐LB had worse attention, executive function, and processing speed. Compared to MCI‐AD, MCI‐LB had better verbal immediate and delayed recall. The MCI‐LB group was worse on all cognitive domains than controls, and better than dementia with Lewy bodies. Studies used different tests and there is a need for global efforts for harmonization.

ABSTRACTBackgroundCorticobasal degeneration (CBD) can present with various clinical phenotypes including Richardson's syndrome (RS). Although neuropathological examination can differentiate CBD and progressive supranuclear palsy (PSP) pathologies, no clinical or imaging findings can differentiate CBD from other pathologies when a patient presents with a variant type of CBD. As these various phenotypes are associated with non‐CBD pathologies, clinical diagnostic accuracy can be low for such patients.ObjectivesTo present clinical features of two cases with symptom progression in line with PSP‐RS, who were diagnosed with CBD based on neuropathological examination.MethodsBaseline, follow up examinations, and detailed neuropathological examinations of two CBD cases presenting and progressing in line with probable PSP‐RS are demonstrated.ResultsThe two cases clinically diagnosed as probable PSP‐RS were shown to have CBD upon neuropathological examination, which is the gold standard for diagnosis of both PSP and CBD.ConclusionsThese cases emphasize the importance of neuropathology for the definite diagnosis, and stress the need for distinctive markers to increase the reliability of clinical diagnosis before death.