Cognitive impairment in children and adults with cerebrotendinous xanthomatosis: A French cohort study.

Cerebrotendinous xanthomatosis is a rare and treatable metabolic disorder related to the accumulation of cholestanol. This disorder is primarily associated with motor and cognitive impairments, although the latter has not been extensively characterized. The objectives of this work were to define the cognitive profile found in cerebrotendinous xanthomatosis patients, investigate the progression of cognitive impairment over time, and search for radio-clinical correlations. Through a multicentric chart review study, we collected cognitive and radiological data from nine children and eighteen adults with genetically proven cerebrotendinous xanthomatosis. We performed a volumetric and morphological analysis of the brain magnetic resonance imaging. In our cohort, 44% (4/9) of children and 78% (14/18) of adults exhibited cognitive impairment that can be severe. The study revealed a significant impairment in various cognitive domains, specifically executive, attentional, language, and visuo-spatial. Among adults, 16% (3/18) developed dementia after age 50. These three patients had delayed chenodeoxycholic acid treatment and important cerebral atrophy. Besides these three cases of late-onset cognitive decline, Mini-Mental State Evaluation was generally stable, suggesting cognitive impairment due to a neurodevelopmental disorder and persisting in adulthood. Cognitive impairment was less common in children, possibly related to early chenodeoxycholic acid treatment in our cohort. The severity of magnetic resonance imaging abnormalities did not predict cognitive impairment in patients. Overall, in cerebrotendinous xanthomatosis, cognitive impairment can be severe and mainly neurodevelopmental. Early chenodeoxycholic acid treatment might be associated with a reduced risk of cognitive decline.

Are we aware of neural activity in primary visual cortex? A neuropsychological case study.

OBJECTIVE: According to a seminal hypothesis stated by Crick and Koch in 1995, one is not aware of neural activity in primary visual cortex (V1) because this region lacks reciprocal connections with prefrontal cortex (PFC). METHODS: We provide here a neuropsychological illustration of this hypothesis in a patient with a very rare form of cortical blindness: ventral and dorsal cortical pathways were lesioned bilaterally while V1 areas were partially preserved. RESULTS: Visual stimuli escaped conscious perception but still activated V1 regions that were functionally disconnected from PFC. INTERPRETATION: These results are consistent with the hypothesis of a causal role of PFC in visual awareness.

Validation study of "Santé-Cerveau", a digital tool for early cognitive changes identification.

BACKGROUND: There is a need for a reliable, easy-to-use, widely available, and validated tool for timely cognitive impairment identification. We created a computerized cognitive screening tool (Santé-Cerveau digital tool (SCD-T)) including validated questionnaires and the following neuropsychological tests: 5 Word Test (5-WT) for episodic memory, Trail Making Test (TMT) for executive functions, and a number coding test (NCT) adapted from the Digit Symbol Substitution Test for global intellectual efficiency. This study aimed to evaluate the performance of SCD-T to identify cognitive deficit and to determine its usability. METHODS: Three groups were constituted including 65 elderly Controls, 64 patients with neurodegenerative diseases (NDG): 50 AD and 14 non-AD, and 20 post-COVID-19 patients. The minimum MMSE score for inclusion was 20. Association between computerized SCD-T cognitive tests and their standard equivalent was assessed using Pearson's correlation coefficients. Two algorithms (a simple clinician-guided algorithm involving the 5-WT and the NCT; and a machine learning classifier based on 8 scores from the SCD-T tests extracted from a multiple logistic regression model, and data from the SCD-T questionnaires) were evaluated. The acceptability of SCD-T was investigated through a questionnaire and scale. RESULTS: AD and non-AD participants were older (mean ± standard deviation (SD): 72.61 ± 6.79 vs 69.91 ± 4.86 years old, p = 0.011) and had a lower MMSE score (Mean difference estimate ± standard error: 1.74 ± 0.14, p < 0.001) than Controls; post-COVID-19 patients were younger than Controls (mean ± SD: 45.07 ± 11.36 years old, p < 0.001). All the computerized SCD-T cognitive tests were significantly associated with their reference version. In the pooled Controls and NDG group, the correlation coefficient was 0.84 for verbal memory, -0.60 for executive functions, and 0.72 for global intellectual efficiency. The clinician-guided algorithm demonstrated 94.4% ± 3.8% sensitivity and 80.5% ± 8.7% specificity, and the machine learning classifier 96.8% ± 3.9% sensitivity and 90.7% ± 5.8% specificity. The acceptability of SCD-T was good to excellent. CONCLUSIONS: We demonstrate the high accuracy of SCD-T in screening cognitive disorders and its good acceptance even in individuals with prodromal and mild dementia stages. SCD-T would be useful in primary care to faster refer subjects with significant cognitive impairment (and limit unnecessary referrals) to specialized consultation, improve the AD care pathway and the pre-screening in clinical trials.