Introduction: Animal research and epidemiological studies identified cholesterol as a risk factor
for mild cognitive impairment (MCI) and Alzheimer's disease (AD). We therefore investigated
the potential impact of plasma total cholesterol (TC) on the development of MCI and
AD in a longitudinal study of a representative birth cohort born between 1930 and
1932. Methods: 500 participants of the Interdisciplinary Longitudinal Study on Adult Development
and Aging (ILSE) were examined in 1993–1996 (t1), 1997–2000 (t2) and 2005–2008 (t3).
Results: Prevalence of MCI increased from 13% to 23% and 29% over time; in addition, 7% of
the participants had developed AD at t3. At t1 and t2 MCI patients showed the highest
TC level and control subjects the lowest with AD patients occupying an intermediate
position. When compared to control subjects, patients with MCI or AD showed a significant
decrease of TC levels between t1 and t3. In all examination waves APOE4 carriers showed
higher TC levels in comparison to the non-APOE4 carriers. Analyses of variance yielded
significant (p<0.05) main effects for diagnosis, presence of an APOE4 allele and
time. The interactions time*diagnose and time*diagnose*APOE also reached significance.
Conclusion: Our findings confirm the hypotheses that high midlife serum TC constitutes a risk
factor for the development of MCI and AD and demonstrate that this effect particularly
strikes at the APOE4 carriers. The reduction of TC among the patients could be explained
by a disease effect.