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Progression to Dementia or Reversion to Normal Cognition in Mild Cognitive Impairment as a Function of Late-Onset Neuropsychiatric Symptoms
McGirr A, Nathan S, Ghahremani M, Gill S, Smith EE, Ismail Z.. Neurology, 2022-03-29
Topic: Risk, prevention and care in population studies
Background and objectives Mild cognitive impairment (MCI) is an at-risk state for dementia; however, not all individuals with MCI transition to dementia, and some revert to normal cognition (NC). Here, we investigate whether mild behavioral impairment (MBI), the late-life onset of persistent neuropsychiatric symptoms (NPS), improves the prognostic specificity of MCI. Methods Participants with MCI from the National Alzheimer's Coordinating Center Uniform Data Set were included. NPS were operationalized with the Neuropsychiatric Inventory Questionnaire to identify participants without NPS and those with MBI (persistent, late-onset NPS). Individuals with late-onset NPS not meeting the MBI persistence criterion (NPS_NOT_MBI) were retained for secondary analyses. Progression to dementia, stable MCI, and reversion to NC after 3 years of follow-up were defined per National Institute on Aging-Alzheimer's Association and Petersen criteria. Results The primary sample consisted of 739 participants (NPS- n = 409 and MBI+ n = 330; 75.16 ± 8.6 years old, 40.5% female). After 3 years, 238 participants (33.6%) progressed to dementia, and 90 (12.2%) reverted to NC. Compared to participants without NPS, participants with MBI were significantly more likely to progress to dementia (adjusted odds ratio [AOR] 2.13, 95% CI 1.52-2.99), with an annual progression rate of 14.7% (vs 8.3% for participants with MCI without NPS). Compared to participants without NPS, participants with MBI were less likely to revert to NC (AOR 0.48, 95% CI 0.28-0.83, 2.5% vs 5.3% annual reversion rate). The NPS_NOT_MBI group (n = 331, 76.5 ± 8.6 years old, 45.9% female) were more likely to progress to dementia (AOR 2.18, 95% CI 1.56-3.03, 14.3% annual progression rate) but not less likely to revert to NC than those without NPS. Accordingly, both NPS_NOT_MBI and MBI+ participants had lower Mini-Mental State Examination scores than NPS- participants after 3 years. Discussion Late-onset NPS improve the specificity of MCI as an at-risk state for progression to dementia. However, only persistent late-onset NPS are associated with a lower likelihood of reversion to NC, with transient NPS (i.e., NPS_NOT_MBI) not differing from the NPS- group. Clinical prognostication can be improved by incorporating late-onset NPS, especially those that persist (i.e., MBI), into risk assessments. Clinical trials may benefit from enrichment with these higher-risk participants with MCI.
Key findings
- Results The primary sample consisted of 739 participants (NPS- n = 409 and MBI+ n = 330; 75.16 ± 8.6 years old, 40.5% female).
- Compared to participants without NPS, participants with MBI were significantly more likely to progress to dementia (adjusted odds ratio [AOR] 2.13, 95% CI 1.52-2.99), with an annual progression rate of 14.7% (vs 8.3% for participants with MCI without NPS).
- Compared to participants without NPS, participants with MBI were less likely to revert to NC (AOR 0.48, 95% CI 0.28-0.83, 2.5% vs 5.3% annual reversion rate).
- However, only persistent late-onset NPS are associated with a lower likelihood of reversion to NC, with transient NPS (i.e., NPS_NOT_MBI) not differing from the NPS- group.
Why it matters
This study found that people with mild cognitive impairment who had late-onset persistent neuropsychiatric symptoms were more likely to progress to dementia and less likely to revert to normal cognition. The findings describe a factor that may help predict progression but do not test any treatment or prevention.
Study details
- Participants409
- Effect size40.5%; 33.6%; 12.2%
- Evidence strengthLow
How this study scored 61/100
Published in a leading specialty journal. Scored zero for study design and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 59 of the 96 points we could judge it on, which is 61 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 409 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 128 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 21.3 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 4 / 6 | Cited 15.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 3 / 4 | Cited 97 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 1 / 3 | University of Calgary: institution h-index 1,028 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35351783) |
| Free to read | 2 / 2 | Free to read |
| Points | 59 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 59 of the 96 points we could judge it on is 61 out of 100. |
| Total | 61 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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
McGirr, A., Nathan, S., Ghahremani, M., Gill, S., Smith, E. E., & Ismail, Z. (2022). Progression to Dementia or Reversion to Normal Cognition in Mild Cognitive Impairment as a Function of Late-Onset Neuropsychiatric Symptoms. Neurology. https://doi.org/10.1212/wnl.0000000000200256
Vancouver
McGirr A, Nathan S, Ghahremani M, Gill S, Smith EE, Ismail Z. Progression to Dementia or Reversion to Normal Cognition in Mild Cognitive Impairment as a Function of Late-Onset Neuropsychiatric Symptoms. Neurology. 2022. doi:10.1212/wnl.0000000000200256. PMID: 35351783.
BibTeX
@article{mcgirr2022-35351783,
author = {McGirr, A. and Nathan, S. and Ghahremani, M. and Gill, S. and Smith, E. E. and Ismail, Z.},
title = {{Progression to Dementia or Reversion to Normal Cognition in Mild Cognitive Impairment as a Function of Late-Onset Neuropsychiatric Symptoms}},
journal = {Neurology},
year = {2022},
doi = {10.1212/wnl.0000000000200256},
pmid = {35351783},
url = {https://doi.org/10.1212/wnl.0000000000200256}
}
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