Table 2.
Characteristics of longitudinal studies investigating relationship between inflammatory markers and vascular dementia
| Study (country) | Mean follow-up | Population | Sample size | Mean age at baseline | Inflammatory biomarkers | Covariates | Diagnostic criteria | Main results |
|---|---|---|---|---|---|---|---|---|
| Miwa, 2016 (Japan) | 7.5 y | Participants form Osaka Follow-up Study for Carotid Atherosclerosis, Part 2 (OSACA2) on high CV risk subjects in primary and secondary prevention with MMSE score ≥ 24 and 0 on the CDR | 803 | 67.0 y | IL-6, CRP [serum] | Age, sex, APO-Eε4, education, variants of IL-6 receptor gene (rs2228145) |
AD: NINCDS-ADRDA criteria VaD: NINDS- AIREN criteria MRI scan |
Higher IL-6 significantly associated with VaD (RR: 1.95, 95% CI: 1.15–3.19, p = 0.017), but this association disappeared when further adjusting for IL-6 receptor gene variant rs2228145 |
| Gallacher, 2010 (England) | 17.3 y |
Men free of vascular disease and not taking anticoagulants at baseline |
865 | From 45 to 59 y | hs-CRP, IL-6, fibrinogen, plasma viscosity, WBC, α2-macroglobulin, α1-antitrypsin [plasma] | Age, social class, systolic pressure, BMI, smoking status, total cholesterol, and alcohol consumption |
AD: NINCDS-ADRDA criteria VaD: NINDS-AIREN criteria Rosen-modified HIS |
Higher fibrinogen associated with VaD (HR: 1.68, 95% CI: 1.02–2.76) Other inflammatory markers not associated with VaD |
| Ravaglia, 2007 (Italy) | 3.7 y | Participants aged 65 years and older free of dementia from the Conselice Study of Brain Ageing | 804 | 73.6 y |
hs-CRP, IL-6 [serum] α1-antichymotrypsin [plasma] |
Age, gender, education, APO-E genotype, history of stroke and cardiovascular disease, physical activity, and BMI |
AD: NINCDS-ADRDA criteria VaD: NINDS-AIREN criteria CT scan |
Higher CRP associated with VaD (HR: 2.93, 95% CI: 1.39–6.18) Combination of high CRP and high IL6 associated with risk of VaD (HR: 2.56, 95% CI: 1.21–5.50) |
| Engelhart, 2004 (Netherlands) | 6–9 y | Participants aged 55 years and older free of dementia from Rotterdam Study | 727 | 71.7 y | ACT, CRP, IL-6, sICAM-1, and sVCAM-1 [plasma] | Age, gender, education, smoking, BMI, diabetes mellitus, use of anti-inflammatory medication, and atherosclerosis |
AD: NINCDS-ADRDA criteria VaD: NINDS-AIREN criteria |
ACT (RR: 2.48) and CRP (RR: 1.31) associated with increased risk of Va Levels of IL-6, sICAM-1 and sVCAM-1 not associated with VaD |
| Schmidt, 2002 (United States) | 25 y | Nested case–control study from Honolulu-Asia Aging Study in Japanese American men | 1,050 | 29.2 y | hs-CRP [serum] | Education, smoking, midlife average cholesterol, midlife blood pressure, age, years of follow-up, APO-Eε4, BMI, stroke, coronary heart disease, left ventricular hypertrophy, atrial fibrillation, diabetes mellitus, ABI at the time of dementia assessment |
AD: NINCDS-ADRDA criteria VaD: California Alzheimer’s Disease Diagnostic and Treatment Centers criteria |
Compared with lowest hs-CRP quartile (< 0.34 mg/L), men in the upper three quartiles had a threefold higher risk for all dementias, AD, and VaD. For VaD, the risk increased with increasing quartile |
| Hsu, 2017 (Taiwan) | 11 y |
Participants aged 65 years and older free of dementia from the Elderly Nutrition and Health Survey in Taiwan |
1,436 | 73.2 y | CRP [serum] |
Age, gender, education, BMI, use of sleep medication, alcohol consumption, and diastolic blood pressure |
Not specified (review of ICD-9-CM code from medical records) | Higher CRP associated with higher risk of VaD (HR: 2.09; 95% CI: 1.01–4.32) but not AD |
| Van Oijen, 2005 (Netherlands) | 5.7 y | Participants aged 55 years and older free of dementia from Rotterdam Study | 6,713 | 69.5 y | Fibrinogen, hs-CRP [plasma] | Cardiovascular risk factors, presence of apoEε4, previous stroke, white blood cell count, and fibrinogen |
AD: NINCDS-ADRDA criteria VaD: NINDS-AIREN criteria |
High fibrinogen levels associated with higher risk of both AD (HR: 1.25, 95% CI: 1.04–1.49) and VaD (HR: 1.76, 95% CI: 1.34–2.30) Higher levels of CRP not associated with higher risk of dementia |
Abbreviations: ABI ankle-brachial index, ACT α1-antichymotrypsin, AD Alzheimer’s disease, APOE apolipoprotein E, BMI body mass index, CI confidence interval, CRP c-reactive protein, CT computed tomography, IL interleukin, HIS Hachinski Ischemic Scale, HR hazard ratio, hs-CRP high sensitive c-reactive protein, MRI magnetic resonance imaging, NINCDS-ADRDA National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and related Disorders Association, NINDS-AIREN National Institute of Neurological Disorders and Stroke–Association Internationale pour la Recherche et l’Enseignement en Neurosciences, RR relative risk, sICAM-1 soluble forms of intercellular adhesion molecule-1, sVCAM-1 vascular cell adhesion molecule-1, VaD vascular dementia