Dementia and neurodevelopmental predisposition: Cognitive dysfunction in presymptomatic subjects precedes dementia by decades in frontotemporal dementia
Bibliographic record
Abstract
Dementia is typically thought of as a disease caused by the process of aging. Few studies have addressed the premorbid neuropsychological alterations in subjects at risk for the disease--an issue of great importance for the understanding and treatment of degenerative dementias. We used knowledge of the mutation carrier status in a family with inherited dementia to address this issue more efficiently than is possible in the general population, or in cases of inherited dementia where the mutational basis is unknown. Standard neuropsychological tests were used to detect evidence of dysfunction in frontal executive systems in 10 presymptomatic subjects with known mutation carrier status in the highly penetrant condition, frontotemporal dementia and parkinsonism linked to chromosome 17. Presymptomatic carriers demonstrated cognitive dysfunction that was not present in 6 nonmutation-carrying relatives. Strikingly, frontal-executive dysfunction was apparent in some of the youngest mutation carriers many decades prior to the predicted onset of dementia. Thus, this dysfunction may reflect the native cognitive capacities of affected subjects. These results suggest a potentially important neurodevelopmental component to a dementing condition that has been predominantly considered to be a disease of aging; accordingly, this issue warrants study in other families to assess the applicability of these findings.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".