Table 1. Factors modifying the progression from MCI to any form of dementia reported in at least one published study.
| Authors,Ref. Year | Sample Size and Cohort Definition | Variable | Outcome Definition | Hazard Ratio (95% CI) | Comment |
|---|---|---|---|---|---|
| Genetics | |||||
| Elias-Sonnenschein et al,73 2011 | Meta-analysis of 35 studies including >6000 subjects | APOE ε4 | Alzheimer-type dementia | 2.29 (1.88–2.80) | Progression to Alzheimer-type dementia in homozygotes: 3.94 (2.09–7.33) |
| Rodriguez-Rodriguez et al,75 2012 | 288 Spanish older adults with MCI | APOE ε4, CLU | Alzheimer-type dementia | APOE ε4: 4.56 (2.23–9.38) CLU: 0.25 (0.07–0.84) | Carriers of at least 6 genetic risk factors increased the risk of more rapid progression (HR 1.89, 95% CI 1.01–3.56) |
| Tyas et al,74 2007 | 470 subjects from the Nun study | APOE ε4 | Any dementia | 1.12 (0.60–2.08) | Age was the only predictor for the progression of MCI to dementia |
| MCI Subtype | |||||
| Ravaglia et al,78 2008 | 60 Italian older adults with MCI; 27 with at least memory-domain MCI | MCI with at least memory impairment | Any dementia or Alzheimer-type dementia | Any: 4.78 (2.83–8.07) Alzheimer: 5.92 (3.30–10.91) | No difference in progression to dementia between those with nonamnestic MCI and those without MCI |
| Zhou et al,79 2012 | 397 older adults with MCI from the ADNI cohort | ADAS13 and CDR-sob scores | Alzheimer-type dementia | 6.9 (4.3–11.0) | High-risk groups included those with ADAS13 >15.67 and CDR-sob >1.5 |
| Koepsell and Monsell,80 2012 | 3020 American older adults with MCI | Nonamnestic single domain, MMSE and CDR scores, and FAQ score | Reversion to normal cognition | Nonamnestic single domain: 1.75 (1.29–2.38) MMSE: 1.21 (1.12–1.30) CDR-sob: 0.66 (0.57–0.77) FAQ ≥1: 0.72 (0.56–0.94) | After 1 year of follow-up, 16% reverted to normal cognition and 20% progressed to dementia. Categorical comparison groups were amnestic single-domain, FAQ score of 0, and APOE ε4 noncarriers |
| Yaffe et al,13 2006 | 305 American older adults with MCI | MCI subtype: reference group was amnestic MCI | Any dementia | Single, nonamnestic: 0.60 (0.35–1.05) Multidomain MCI: 0.71 (0.44–1.14) | MCI subtype predicted dementia type: amnestic MCI more likely to develop Alzheimer-type dementia; single nonamnestic MCI predicted FTD |
| Comorbidity | |||||
| Solfrizzi et al,91 2011 | 121 Italian older adults | Metabolic syndrome | Any dementia | 7.80 (1.29–47.20) | Metabolic syndrome did not increase risk of incident MCI |
| Li et al,92 2012 | 257 Chinese older adults with MCI | MRI, CTA, and clinical characteristics | Any dementia | Diabetes: 2.39 (1.07–5.33) WMC: 0.06 (0.02–0.20) Carotid stenosis: 159.06 (4.57–5537.67) | Similar risk of progression to Alzheimer-type dementia |
| Clerici et al,93 2012 | 245 Italian older adults receiving care in a memory disorders clinic | MRI and clinical characteristics | Any or Alzheimer-type dementias | Combination of ≥1 deep WML and HIS ≥4: 3.5 (1.6–7.4) | Similar result for the association with Alzheimer-type dementia |
| Xu et al,98 2010 | 302 Swedish older adults with MCI | Diabetes or prediabetes | Any or Alzheimer-type dementias | 3.89 (1.69–8.32) | Similar risk of Alzheimer-type as with any dementia. Markers of disease control not considered |
| DeCarli et al,95 2004 | 52 American adults with MCI visiting a memory clinic | Vascular risk factors | Alzheimer-type dementia (by CDR-sob score) | Not significantly different, no HR reported | Poor memory and executive function increased the risk of progression to Alzheimer-type dementia |
| Li et al,99 2011 | 837 Chinese older adults with MCI | Vascular risk factors | Alzheimer-type dementia | Treatment reduced Alzheimer dementia | Treatment of more risk factors reduced the risk more than treatment of fewer risk factors |
| Ravaglia et al,94 2006 | 165 Italian older adults with MCI | Vascular risk factors | Any dementia | Diastolic blood pressure: 0.52 (0.32–0.84) Atrial fibrillation: 4.94 (1.89–12.88) | After adjusting for confounders, neither nor hypertension |
| Bettermann et al,100 2012 | American older adults with MCI | Statin use | All-cause and Alzheimer-type dementia | No difference between users and nonusers | Statin use reduced the risk of incident dementia in cognitively normal subjects |
| Neuropsychiatric Symptoms | |||||
| Richard et al,108 2012 | 320 older adults from Manhattan, NY, USA | CES-D ≥4 | Any dementia | 1.8 (1.0–3.1) | Nonsignificant increase in risk of Alzheimer-type dementia |
| Richard et al,104 2012 | 397 older adults from ADNI | GDS-15—3-item Apathy score | Alzheimer-type dementia | 1.85 (1.09–3.15) | Effect only significant in those without depression. A GDS score of ≥6 was an exclusion for the ADNI study |
| Modrego and Ferrandez,105 2004 | 45 Italian older adults with MCI | Depression (GDS and structured interview) | Alzheimer-type dementia | 2.6 (1.8–3.6) | |
| Palmer et al,106 2007 | 47 Swedish older adults with MCI | Comprehensive Psychopathological Rating Scale | Alzheimer-type dementia | 1.8 (1.2–2.7) | Depressed mood increased risk of progression to Alzheimer in cognitively normal subjects |
| Reynolds et al,107 2011 | 57 American older adults with MCI and depression | Antidepressants with or without donepezil | Any dementia | NR; Reduced rate of progression to dementia (10% vs 33%) | Higher risk of recurrent depression (likelihood ratio: 4.91; P = .03) |
Abbreviations: ADAS13, Alzheimer's Disease Assessment Scale with 13 items; ADNI, Alzheimer's Disease Neuroimaging project; APOE, apolipoprotein; CDR-sob, Clinical Dementia Rating scale sum of boxes; CES-D, Center for Epidemiological Studies Depression; CI, confidence interval; CLU, clusterin; CTA, computed tomographic angiography; FAQ, Functional Activities Questionnaire; FTD, frontotemporal dementia; GDS, Global Deterioration Scale; HIS, Hachinski Ischemic Score; MCI, mild cognitive impairment; MMSE, Mini-Mental Status Examination; MRI, magnetic resonance imaging; MTL, medial temporal lobe; NR, not reported; WML, white matter lesions.