Cognitive impairment in sporadic ALS
Bibliographic record
Abstract
BACKGROUND: Traditionally considered a motor neuron-selective disorder, the clinical manifestations of ALS can include a frontotemporal dementia. Although the pathologic substrate of cognitive impairment remains to be defined, the presence of ubiquitin-immunoreactive (Ub+) intraneuronal inclusions in cortical regions has been suggested to constitute a pathologic marker of this process. METHODS: The authors compared the neuropathological features of four cognitively impaired patients with ALS, four cognitively intact patients with ALS, and four neurologically normal patients. The extent and load of Ub+ neuronal inclusions, Ub+ dystrophic neurites, and superficial linear spongiosis (SLS) was determined among a number of cortical, hippocampal, and subcortical regions. RESULTS: Although Ub+, alpha-synuclein-negative, and tau-negative neuronal inclusions were observed in both cognitively impaired and cognitively intact patients with ALS, their density and extent was greater among the former, with the difference greatest in the cingulate gyrus. Ub+ neurites were observed in a similar distribution. Only the presence of SLS, affecting the first and second cortical layers, reliably distinguished between the cognitively impaired and cognitively intact ALS subpopulations. In three of four cognitively impaired patients with ALS, SLS was associated with transcortical microglial activation, in the absence of detectable differences in astrocytosis, density of calbindin or parvalbumin neurons, or optical density of synaptophysin and SNAP-25. CONCLUSIONS: Although intraneuronal Ub+ inclusions and dystrophic neurites are observed in both ALS subpopulations, the presence of cognitive impairment was associated with a greater distribution and load of both neuropathologic features, suggesting a disease continuum. Moreover, cognitive impairment was uniformly associated with superficial linear spongiosis, a pathologic feature common to several forms of frontotemporal dementia.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.011 | 0.008 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".