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Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy
Takeda S, Sato N, Morishita R.. Frontiers in aging neuroscience, 2014-07-29
Topic: Amyloid, tau and blood-test diagnosis
The incidence of dementia is increasing at an alarming rate, and has become a major public health concern. Alzheimer disease (AD) is the most common form of dementia and is characterized by progressive cognitive impairment. In addition to classical neuropathological features such as amyloid plaques and neurofibrillary tangles (NFT), accumulation of activated immune cells has been documented in the AD brain, suggesting a contribution of neuroinflammation in the pathogenesis of AD. Besides cognitive deterioration, non-cognitive symptoms, such as agitation, aggression, depression and psychosis, are often observed in demented patients, including those with AD, and these neuropsychological symptoms place a heavy burden on caregivers. These symptoms often exhibit sudden onset and tend to fluctuate over time, and in many cases, they are triggered by an infection in peripheral organs, suggesting that inflammation plays an important role in the pathogenesis of these non-cognitive symptoms. However, there is no mechanistic explanation for the relationship between inflammation and neuropsychiatric symptoms. Observations from experimental mouse models indicate that alteration of brain blood vessels, especially blood-brain barrier (BBB) dysfunction, may contribute to the relationship. The current review summarizes the results from recent studies on the relationship between inflammation and AD, while focusing on cerebrovascular alterations, which might provide an insight into the pathogenesis of cognitive/non-cognitive symptoms in AD patients and suggest a basis for the development of new therapeutic treatments for these conditions.
Key findings
- These symptoms often exhibit sudden onset and tend to fluctuate over time, and in many cases, they are triggered by an infection in peripheral organs, suggesting that inflammation plays an important role in the pathogenesis of these non-cognitive symptoms.
- Observations from experimental mouse models indicate that alteration of brain blood vessels, especially blood-brain barrier (BBB) dysfunction, may contribute to the relationship.
- The current review summarizes the results from recent studies on the relationship between inflammation and AD, while focusing on cerebrovascular alterations, which might provide an insight into the pathogenesis of cognitive/non-cognitive symptoms in AD patients and suggest a basis for the development of new therapeutic treatments for these conditions.
Why it matters
This review suggests that inflammation, possibly through blood-brain barrier dysfunction, may contribute to both cognitive and non-cognitive symptoms in Alzheimer's disease. The evidence for the blood-brain barrier link comes from experimental mouse models, so it is preliminary and does not yet provide a treatment or cure.
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Study details
- Evidence strengthLow
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in aging neuroscience) |
| Journal's citation record | 2 / 4 | Frontiers in Aging Neuroscience: journal h-index 174 (OpenAlex, 2026-10-29) |
| 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 | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2014 — within 20 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 | 5 / 7 | Cited 223 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.9 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 4 / 6 | Cited 17.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 2 / 4 | Cited 31 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Ryuichi Morishita: h-index 90 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | The University of Osaka: institution h-index 1,138 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25120476) |
| Free to read | 2 / 2 | Free to read |
| Total | 45 / 100 | — |
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Read the original
- DOI: 10.3389/fnagi.2014.00171
- PubMed: 25120476
- Original source →
- Free full text: Frontiers in Aging Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Takeda, S., Sato, N., & Morishita, R. (2014). Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy. Frontiers in aging neuroscience. https://doi.org/10.3389/fnagi.2014.00171
Vancouver
Takeda S, Sato N, Morishita R. Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy. Frontiers in aging neuroscience. 2014. doi:10.3389/fnagi.2014.00171. PMID: 25120476.
BibTeX
@article{takeda2014-25120476,
author = {Takeda, S. and Sato, N. and Morishita, R.},
title = {{Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy}},
journal = {Frontiers in aging neuroscience},
year = {2014},
doi = {10.3389/fnagi.2014.00171},
pmid = {25120476},
url = {https://doi.org/10.3389/fnagi.2014.00171}
}
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