Relationships between neurodegeneration and neurodevelopment have long been noted. However, the magnitude and etiopathogenesis of these relationships have not been clear. The relationship between a widely used, neurodevelopmentally based, functional measure of AD course, the Functional Assessment Staging procedure (FAST, Sclan & Reisberg, International Psychogeriatrics, 1992), and the cognitively based MMSE, was studied. The 1507 otherwise healthy participants comprised 376 cognitively normal, 243 MCI, and 888 AD subjects. The 16 ordinal FAST stages and substages were divided into 9 FAST levels for some analyses. A strong monotonic relationship was observed between the two conceptually independent assessments (Spearman r = –0.90, p < 0.0001). The Wilcoxon rank sum test showed significant differences between each consecutive FAST level in MMSE scores (p<0.0001, except levels 8 and 9, p<0.05). Age, education, gender and mean number of co–morbid conditions did not alter the Spearman rank correlation between the FAST and the MMSE. The reverse relationship between neurodevelopment and neurodegeneration supported by the present findings and prior observations has been termed retrogenesis (Reisberg, et al., Eur. Arch. Psychiatry Clin. Neurosci., 1999). We hypothesized that the retrogenesis relationship could be accounted for if the most neurometabolically active brain regions, subsuming the most recently acquired functional capacities, are affected sequentially by AD related pathology (Reisberg, et al., Am. J. Alz., Dis., 2002). Recent findings have supported this hypothesis indicating that neurometabolic change in normal elders is a predictor of subsequent decline (de Leon, et al., PNAS, 2001), and that the most metabolically active brain regions at rest are subsequent sites of β–amyloid deposition (Buckner, et al., J. Neurosci., 2005). Furthermore, interference with IGF–1, produces AD like neuropathologic changes in rodents (Carro, et al., Neurobiol. Aging, in press). Hence, it now appears that neurohormonal and neurometabolic changes antedate other AD pathologies and these changes appear to link clinical retrogenic, neuropathologic and neuroimaging AD observations. In AD the time course of the retrogenic process also reverses, in many ways, the human temporal developmental sequence (Reisberg, Geriatrics, 1986). This latter phenomenon is consistent with developmental genetic antagonistic pleiotropy as a primary pathogenic event.