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Predicting Rates of Cognitive Decline in Older Adults with Brain- and Cardiac-Imputed Transcripts
Razavi A, Tucker NR, Ghosh AJ, Faraone SV, Glatt SJ, Hess JL.. medRxiv, 2026-09-30
Topic: Genetics and APOE
Severe cognitive decline due to dementia is an important clinical indicator signaling neurodegeneration. Predicting cognitive decline rates can be useful in establishing prognosis and modifying treatment regimens. The rate of decline is highly variable across patients with dementia and may be determined by an interplay of many factors. This variability poses challenges to existing tools for predicting disease progression. Changes in heart and brain tissue have been associated with cognitive decline, yet tissue-specific molecular data are difficult to obtain. In this study, we sought to estimate cognitive decline-related transcripts in the brain and heart of people actively living with and without dementia. We reconstructed transcriptomic profiles in brain and heart with the transcriptome-imputation algorithms BrainGENIE and HeartGENIE, and identified several hundreds of transcripts associated with cognitive decline over a two-year assessment window, with the cerebellar hemisphere, left ventricle of the heart, and atrial appendage showing the largest number of cognitive-related transcripts. Pathway analysis revealed an enrichment among cognition-related transcripts of gene sets involved in synaptic, proteostasis/autophagy, immunologic, and mitochondrial respiratory chain functioning. Hundreds of perturbagens show significant concordance with cognitive decline-related transcriptomic signatures in brain and heart, pointing to potentially druggable targets. Top brain- and heart-specific cognition-associated transcripts were incorporated into LASSO regression models predicting future cognitive decline and were compared to two models, one utilizing age, sex and educational attainment, and a hybrid model incorporating both data types. Our models were able to achieve statistically significant correlations in the test set, yet had weak overall. Together, these findings demonstrate that brain and heart transcriptomes capture distinct aspects of biology related to cognitive decline, providing more nuanced insights into normal and aberrant brain aging that may inform drug-repurposing and risk-prediction efforts.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Razavi, A., Tucker, N. R., Ghosh, A. J., Faraone, S. V., Glatt, S. J., & Hess, J. L. (2026). Predicting Rates of Cognitive Decline in Older Adults with Brain- and Cardiac-Imputed Transcripts. medRxiv. https://doi.org/10.64898/2026.09.29.26364189
Vancouver
Razavi A, Tucker NR, Ghosh AJ, Faraone SV, Glatt SJ, Hess JL. Predicting Rates of Cognitive Decline in Older Adults with Brain- and Cardiac-Imputed Transcripts. medRxiv. 2026. doi:10.64898/2026.09.29.26364189.
BibTeX
@article{razavi2026-ae7b701b,
author = {Razavi, A. and Tucker, N. R. and Ghosh, A. J. and Faraone, S. V. and Glatt, S. J. and Hess, J. L.},
title = {{Predicting Rates of Cognitive Decline in Older Adults with Brain- and Cardiac-Imputed Transcripts}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.09.29.26364189},
url = {https://doi.org/10.64898/2026.09.29.26364189}
}
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Key findings
- Changes in heart and brain tissue have been associated with cognitive decline, yet tissue-specific molecular data are difficult to obtain.
- We reconstructed transcriptomic profiles in brain and heart with the transcriptome-imputation algorithms BrainGENIE and HeartGENIE, and identified several hundreds of transcripts associated with cognitive decline over a two-year assessment window, with the cerebellar hemisphere, left ventricle of the heart, and atrial appendage showing the largest number of cognitive-related transcripts.
- Pathway analysis revealed an enrichment among cognition-related transcripts of gene sets involved in synaptic, proteostasis/autophagy, immunologic, and mitochondrial respiratory chain functioning.
- Hundreds of perturbagens show significant concordance with cognitive decline-related transcriptomic signatures in brain and heart, pointing to potentially druggable targets.
- Top brain- and heart-specific cognition-associated transcripts were incorporated into LASSO regression models predicting future cognitive decline and were compared to two models, one utilizing age, sex and educational attainment, and a hybrid model incorporating both data types.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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