Longitudinal results in the CN population and MCI and sporadic AD cases Different measures of plasma A?? have been associated with progression to dementia (Table ?(Table4):4): high baseline A??1-42 [30,57], low baseline A??1-42/A??1-40 [58,59], low baseline A??1-40 read more or A??1-42 [60], high baseline A??1-40 [29], high A??1-40 or low A??1-42/A??1-40 [61] and low A??1-40 in older subjects [62]. Finally, other studies found no associations of plasma A?? levels with progression to dementia [10,13,63]. A study including information on vascular risk factors in midlife and a long follow-up period after baseline plasma sampling found an increased risk of dementia in subjects with low A??1-40 and A??1-42 at baseline and there was an interaction between plasma A?? levels and diastolic blood pressure that indicated a higher incidence of dementia in subjects with higher diastolic blood pressure and low plasma A?? levels [60].

One study that compared A?? plasma levels in CN and MCI subjects who remained cognitively stable or progressed to AD found no differences in these two different cohorts [13], but, as noted above, there were significant differences based on the CSF-defined groups. Table 4 Longitudinal studies in populations including sporadic Alzheimer’s disease patients Other studies measuring plasma A?? levels included correlations of these values with cognitive measures instead of using a diagnosis as outcome. One study included 481 subjects with a long follow-up and repeated measurements, and it used repeated brief telephone interviews for determining the study outcome, and the authors reported greater cognitive decline in subjects with a low A??1-42/A??1-40 at baseline [64].

However, interassay CV was over 30% (repeated subject measurements were included in the same assay with CV <10%). A larger study of 997 CN subjects followed for 9 years also found a faster cognitive decline in subjects with a lower A??1-42/A??1-40 at baseline [65]. Cosentino et al. [66] followed 880 subjects for 4.5 years who were CN at baseline or had cognitive impairment that was not severe enough for a dementia diagnosis. In this study, subjects with higher baseline A??1-40 and A??1-42 and stable or decreasing A??1-42 levels during follow-up had a faster rate of decline, whereas A??1-42/A??1-40 showed no such association. On the other hand, in another study by Locascio et al.

[67], the rate of cognitive decline in 122 AD patients was Entinostat determined in subjects followed for 4.2 years, and these authors described a faster decline in subjects with lower plasma A??1-40 and A??1-42 at baseline. Two studies found an interaction between cognitive reserve ref 1 and A?? plasma levels, indicating that subjects with lower cognitive reserve showed a greater decline associated with A?? levels [10,65].