The aim of the study was to investigate the behavioral phenotype of patients affected with Bardet-Biedl syndrome (BBS). Twenty-four patients with molecularly confirmed diagnosis of BBS (6-38 years old) were evaluated using standardized neuropsychological tests. Results were compared with normative data. The mean intellectual functioning of participants fell 1.5 standard deviations below normal expectations; though, the majority of participants (75-80%) did not display an intellectual disability. The group's mean performance on most cognitive tasks and all scales of adaptive functioning was significantly weaker than norms. The majority (55-60%) of participants displayed broadly average verbal fluency and auditory rote learning, while 22-40% were severely impaired in the same areas. The majority of participants were severely impaired in perceptual reasoning (53%), attentional capacity (69%), and functional independence (74%). Symptoms associated with Autism were reported for 77% of participants. Behavioral issues were unrelated to intellectual ability but significantly correlated with adaptive functioning. This first neurocognitive evaluation of a molecularly confirmed cohort of BBS patients shows that the majority of patients experience significant difficulties with perceptual intellectual abilities, auditory attentional capacity, adaptive independence, and behavior. The frequency of autism-related symptoms far exceeds the incidence rate of diagnosed autism in general and warrants further investigations.

It remains unclear to what extent cerebrovascular burden relates to amyloid beta (Aβ) deposition, neurodegeneration, and cognitive dysfunction in mixed disease populations with small vessel disease and Alzheimer's disease (AD) pathology. In 120 subjects, we investigated the association of vascular burden (white matter hyperintensity [WMH] volumes) with cognition. Using mediation analyses, we tested the indirect effects of WMH on cognition via Aβ deposition ( 18 F-AV45 positron emission tomography [PET]) and neurodegeneration (cortical thickness or 18 F fluorodeoxyglucose PET)in AD signature regions. We observed that increased total WMH volume was associated with poorer performance in all tested cognitive domains, with the strongest effects observed for semantic fluency. These relationships were mediated mainly via cortical thinning, particularly of the temporal lobe, and to a lesser extent serially mediated via Aβ and cortical thinning of AD signature regions. WMH volumes differentially impacted cognition depending on lobar location and Aβ status. In summary, our study suggests mainly an amyloid-independent pathway in which vascular burden affects cognitive function via localized neurodegeneration.

No abstract

Purpose To characterize a series of seven patients with cone-rod dystrophy (CORD) and amelogenesis imperfecta (AI) due to confirmed mutations in CNNM4, first described as ‘Jalili Syndrome’. Design Retrospective observational case series. Methods Seven patients from six families with Jalili Syndrome were identified at three tertiary referral centers. We systematically reviewed their available medical records, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence imaging (FAF), color fundus photography, and electrophysiological assessments. Results The mean age at presentation was 6.7 years (range 3 - 16), with six male and one female patient. CNNM4 mutations were identified in all patients. The mean Snellen best-corrected visual acuity (BCVA) at presentation was 20/246 (range 20/98 - 20/399) in the right eye and 20/252 (range 20/98 - 20/480) in the left. Nystagmus was observed in all seven patients, and photophobia was present in six. Fundoscopic findings at presentation were variable, ranging from only mild disc pallor to retinal vascular attenuation and macular atrophy. Multimodal imaging demonstrated disease progression in all seven patients over time. Electroretinography uniformly revealed progressive cone-rod dysfunction. Conclusions Jalili Syndrome is a rare CORD associated with AI. We have further characterized its ocular phenotype, including describing SD-OCT, FAF and electrophysiological features; and report several novel disease-causing sequence variants. Moreover, this study presents novel longitudinal data demonstrating structural and functional progression over time, allowing better informed advice on prognosis.