Fourth, another possible explanation was that the effect of CRP on rate of decline may take place before the age of 65, given various studies suggesting that age-related cognitive decline accelerates during midlife [45], and that higher levels of CRP during midlife are associated with a steeper rate of cognitive decline [19], white matter disease [46, 47], and higher risk of dementia in late-life [6]. This evidence concerns the gene CRP and dementia.