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Building Cognitive Lines of Defense: A Life-Course Prevention Strategy for Alzheimer's Disease—An Evidence-Based Multi-Stage Intervention Protocol
ZHONG M.. Research Square, 2026-07-28
Topic: Brain imaging, connectivity and assessment
Background Alzheimer's disease (AD) has become a major global public health crisis, with > 99% failure rate of disease-modifying therapies in phase III trials. Late initiation of intervention is the core issue. Approximately 40% of dementia cases are preventable through risk factor intervention, and AD pathology begins 20–30 years before clinical symptoms. Evidence from 2024 identifies ages 18–39 as a critical prevention window. Objective To systematically synthesize evidence on life-course AD prevention, construct a "Cognitive Fortress" theoretical framework, and develop community-based assessment tools and intervention pathways. Methods Systematic searches of PubMed, Cochrane, and Web of Science (inception to March 2026) yielded 90 included studies (18 RCTs, 52 cohorts, 20 systematic reviews). Quality was assessed using PRISMA, RoB 2.0, ROBINS-I, and AMSTAR-2. Evidence levels followed OCEBM 2011 criteria. Results ① Risk factors across four life stages were identified: early life (< 18y) low education (Level I); young adulthood (18-39y) hypertension, obesity, smoking/TBI, inflammatory markers, hearing loss (Level II); midlife (40-65y) hypertension, type 2 diabetes (Level I); late life (> 65y) hearing loss, depression (Level I). ② The four-line "Cognitive Fortress" framework was constructed: Line 1 Cognitive Reserve (early life), Line 2 Risk Surveillance (young adulthood), Line 3 Neuroprotection (midlife), Line 4 Compensatory Mechanisms (late life). ③ A 10-item risk scale and three-tier intervention pathway were developed. Conclusions AD prevention must transcend the "geriatric disease" mindset. A life-course, multi-stage intervention strategy can effectively delay or prevent clinical AD onset. The four-line framework provides actionable theoretical guidance for community-based AD prevention.
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APA 7th
ZHONG, M. (2026). Building Cognitive Lines of Defense: A Life-Course Prevention Strategy for Alzheimer's Disease—An Evidence-Based Multi-Stage Intervention Protocol. Research Square. https://doi.org/10.21203/rs.3.rs-10476642/v1
Vancouver
ZHONG M. Building Cognitive Lines of Defense: A Life-Course Prevention Strategy for Alzheimer's Disease—An Evidence-Based Multi-Stage Intervention Protocol. Research Square. 2026. doi:10.21203/rs.3.rs-10476642/v1.
BibTeX
@article{zhong2026-9d3fb2a4,
author = {ZHONG, M.},
title = {{Building Cognitive Lines of Defense: A Life-Course Prevention Strategy for Alzheimer's Disease—An Evidence-Based Multi-Stage Intervention Protocol}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10476642/v1},
url = {https://doi.org/10.21203/rs.3.rs-10476642/v1}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Results ① Risk factors across four life stages were identified: early life (< 18y) low education (Level I); young adulthood (18-39y) hypertension, obesity, smoking/TBI, inflammatory markers, hearing loss (Level II); midlife (40-65y) hypertension, type 2 diabetes (Level I); late life (> 65y) hearing loss, depression (Level I). ② The four-line "Cognitive Fortress" framework was constructed: Line 1 Cognitive Reserve (early life), Line 2 Risk Surveillance (young adulthood), Line 3 Neuroprotection (midlife), Line 4 Compensatory Mechanisms (late life). ③ A 10-item risk scale and three-tier intervention pathway were developed.
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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 randomised / 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 multi-centre 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 (Research Square) |
| 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) |
| Randomised / blinded | 0 / 2 | No randomisation 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 |
| Multi-centre 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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