In this large prospective study of older women at high vascular risk, we observed no overall association between dietary fat intake and cognitive decline over 5-years follow-up. However, older age significantly modified the association: in older women (>72 y), substitution of carbohydrates with mono- or polyunsaturated fats was associated with a significantly slower rate of cognitive decline, which was cognitively equivalent to delaying aging by about 4-6 years.
Because several types of fats, cognitive outcomes and subgroup analyses were examined, the effect modification by older age may have been due to chance and thus, these results should be interpreted with caution. However, as older participants have a faster rate of cognitive decline than younger participants, differences in rates are easier to detect in the oldest strata. This fact may underlie our observation of protective associations with higher mono- and poly-unsaturated fat intake only among the subset of older women. This is consistent with other studies of types of fat intake on cognitive aging among populations at high vascular risk (Beydoun et al., 2008
, Devore et al., 2009
). Notably, in a study by Devore et al., which focused on women ≥70 years with type 2 diabetes in the Nurses’ Health Study (mean follow-up: 1.8 years), protective associations with higher intake of unsaturated fats was observed in relation to cognitive decline (Devore et al., 2009
The modulation of vascular processes is likely a key-element to understand how dietary fat composition could indirectly act on the brain in persons with preexisting CVD. Secondary prevention trials to increase polyunsaturated fat and/or reduce saturated fats have found lower recurrence of cardiovascular events (Leren, 1966
, Tuttle et al., 2008
), conditions that have been closely associated with higher cognitive risk (de la Torre, 2006
). Increased dietary intake of polyunsaturated fatty acids may also act on the brain in enhancing neurotransmission, neuroprotection, and neurogenesis, partly via antioxidant and anti-inflammatory effects (Lindqvist et al., 2006
, Yehuda et al., 2005
). Interestingly, in the oldest women, we observed that higher intakes of mono-and poly-unsaturated fats at baseline was associated with lower subsequent risks of decline in both the global composite score and verbal composite score. However, we did not detect any such associations with the category fluency test. This specificity of the association to different outcomes, each representing different cognitive domains, underscores the complexity of the potential etiologic pathway between dietary fat intake and cognitive decline. Although a number of animal studies (de Wilde et al., 2002
, Winocur and Greenwood, 2005
) support a neuroprotective effect of unsaturated fats, plausible mechanisms have not been fully elucidated, and results from human studies remain inconclusive (Fotuhi et al., 2009
). In particular, epidemiologic data are scarce for populations at high vascular risk.
Our study had several strengths. The data from the WACS cognitive cohort included a detailed dietary assessment with information on various fat intakes and four repeated cognitive assessments. We adjusted for a wide array of potential confounders, including various dietary, health, medication and lifestyle factors.
Nonetheless, some methodological issues should be considered. It is possible that a single assessment of fat consumption in late adulthood does not reflect the long-term dietary intakes of participants, which may be more etiologically relevant. This may be particularly true in our population of women at high cardiovascular risk, who were probably encouraged to change their diet. To address this, we carefully adjusted the analyses on participants’ cardiovascular profiles at enrollment (which may provide an indicator of the severity of the condition) and conducted subgroup analyses only among women who reported at enrollment that their diet changed very little in the past five years. Overall, our main “null result” was robust, since we did not observe that the findings were different from the main analyses. A limitation was that we lacked updated dietary data after baseline, however, because of the possibility of reverse causation (i.e., participants who experience slight cognitive change may actively change their diet) such analyses may have inherent biases, and the analyses with baseline diet would be preferred. Second, a telephone cognitive assessment might lack validity. However, both reliability and validity studies of our telephone instrument have provided convincing evidence of its utility to evaluate cognitive function in an epidemiologic study. In addition, using a similar telephone battery, significant associations with cognitive aging have been found with a large number of risk factors, including dietary variables (Kang et al., 2005
, Lee et al., 2006
). Finally, participants were mostly Caucasian, which precludes extending our findings to other ethnic minorities.
In a large sample of community-dwelling women aged ≥65 with pre-existing cardiovascular disease or risk factors, no associations were observed between intakes of various fats with 5-year cognitive decline. However, a trend toward a possible beneficial effect of unsaturated fats for preserving cognitive function in oldest women warrants further study.