Table 1.
Meta-analyses since 2009 on the association between elevated plasma homocysteine and dementia or AD in prospective cohort studies
| Meta-analysis | Studies/Subjects/Duration | Exposure threshold | Outcome | Pooled risk estimates (95% CI) | PAR% (95% CI) [Prev. 0.25] | PAR% (95% CI) [Prev. 0.30] |
| Van Dam, et al. [44] | 3 prospective studies in 2,569 subjects (baseline free of AD) | tHcy >14.0, 15.0, or 15.6 μmol/L | Alzheimer’s disease | RR: 2.5 (1.38–4.56) | 27.3 (7.5–47.1) | 31.0 (8.6–53.5) |
| Wald et al. [45] | 8 cohorts of 8,669 subjects, median duration = 5 years. Cohort studies of individuals without cognitive impairment or dementia at the start of the study which reported serum homocysteine levels and the incidence or risk of dementia after at least 1 year of follow-up were included. | For a 5 μmol/L increase in tHcy (i.e., 10.0 ⟶ 15.0 μmol/L) | Dementia (the search criteria was mixed, memory, dementia, etc.) | Adjusted OR: 1.50 (1.13–2.0) | / | / |
| Beydoun et al. [17] | 5 cohorts on 4,412 subjects | Elevated tHcy (variety of cut-offs: 14.0, 15.0, 15.6, 14.6 and 12.6 μmol/L) | Incident AD | RR: 1.93 (1.50–2.49) | 18.9 (10.8–27.0) | 21.8 (12.5–31.1) |
| Nie et al. [46] | 14 cohorts on 15,908 subjects | Elevated tHcy (variety of cut-offs: 15.8, 15.0, 14.0, 27.5, 15.4, 15.0, 13.4, 13.0, 14.3, 21.0, 15.1, 14.5, 17.0 [?], 10.8 μmol/L) | Dementia, cognitive impairment | RR: 1.53 (1.23–1.9) | 11.7 (3.8–19.6) | 13.7 (6.3–21.2) |
| Shen et al. [47] | 9 studies on 4,830 subjects (mixed study designs) | Elevated tHcy (variety of cut-offs: 14, 12.0, 13.1, 13.3, 27.4, 15.0, 13.0, 15.0 μmol/L) | AD | RR: 1.77 (1.37–2.16) | 16.1 (9.1–23.1) | 18.8 (10.7–26.9) |
| Xu et al. [15] | 8 cohort studies on 5728 subjects | Elevated tHcy same as Shen et al. [47] | AD | RR: 1.15 (1.02–1.27) | 3.6 (0.69–6.51) | 4.3 (0.84–7.8) |
| Hu et al. [16] | 34 cohort studies on 9,397 subjects | Mendelian randomisation of the MTHFR C677T as a cause for AD | AD | OR TT versus CC: 1.37 (1.15–1.63). OR CT versus CC 1.28 (1.14–1.44). OR (for each 1 SD increase in ln(tHcy)): 3.37 (1.9–5.95) |
AD, Alzheimer disease; CI, confidence intervals; tHcy, total homocysteine; MTHFR, methylentetrahydrofolate reductase; OR, odds ratio; PAR, Population Attributable Risk; Prev, prevalence of hyperhomocysteinemia (HHCY); RR, relative risk; SD, standard deviation. It should be noted that many of the meta-analyses included the same cohorts. PAR = 100 * [P(HHCY) * (RR–1)] / 1 + [P(HHCY) * (RR–1)]. 95% CI of PAR are according to Beydoun et al. [17] and the references cited there.