Cognitive and Behavioral Abnormalities in FTD Mutation Carriers: Insights into Shared Mechanisms with ADD/ADHD Disorder
Bibliographic record
Abstract
BACKGROUND: Frontotemporal dementia (FTD) is a neurodegenerative disorder marked by early impairments in executive function and altered prefrontal neural circuitry. These traits are also observed in Attention Deficit Disorder (ADD) and Attention Deficit Hyperactivity Disorder (ADHD), suggesting the possibility of shared mechanisms and a role for developmental neurocognitive factors in the onset of FTD. High-penetrance mutations in GRN, C9orf72, and MAPT increase FTD risk and are suspected to influence neurodevelopment. This study hypothesizes that pre-symptomatic carriers of these mutations exhibit cognitive and behavioral traits that overlap with those observed in ADD/ADHD. METHOD: This cross-sectional study analyzed participants from the ARTFL-LEFFTDS Longitudinal FTLD (ALLFTD) Study. Inclusion criteria restricted the sample to mutation carriers with pathogenic variants in GRN, C9orf72, or MAPT while excluding individuals with prior psychiatric diagnoses (e.g., bipolar disorder, major depressive disorder) and those taking antipsychotic or anxiolytic medications to avoid potential confounding effects on test validity and interpretation. The final sample included N = 338 participants, categorized as pre-symptomatic mutation carriers (N = 227) or asymptomatic noncarriers (N = 111). To assess potential overlaps with ADD/ADHD traits, a targeted subset of measures reflecting executive function, working memory, attention, social behavior, and hyperactivity were extracted from validated cognitive and neuropsychiatric assessments. Mutation carriers were further classified as either converters (N = 20) who progressed to symptomatic FTD (CDR ≥ 1) or non-converters (N = 95) who remained asymptomatic. Only pre-conversion scores were analyzed for converters. Group comparisons were conducted using general linear models adjusted for age and sex. RESULT: Pre-symptomatic mutation carriers showed significantly lower verbal fluency (p = 0.004) and a trend toward reduced working memory (p = 0.05) compared to noncarriers. Converters exhibited poorer overall cognitive performance (p <0.0001), verbal fluency (p = 0.001), and memory and attention (p = 0.04) compared to non-converters. Converters demonstrated higher Neuropsychiatric Inventory scores (p = 0.0001), particularly in hyperactivity (p = 0.003), reflecting greater behavioral disturbances. CONCLUSION: Baseline impairments in cognitive function, memory, and neuropsychiatric profiles distinguish converters from non-converters, highlighting overlaps between ADD/ADHD traits and prodromal FTD. These findings suggest shared neurobiological mechanisms and underscore the need for mutation-specific studies to further explore the neurodevelopmental factors driving FTD progression.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".