An interesting inference derived from our observations is that the deposition of amyloid in the OO does not appear to be critical for the development of dementia, since these individuals can possess high plaque scores and be non-demented. Dementia is clearly more associated with age-related vascular dysfunction and the spread of NFT throughout the EPZ004777 hydrochloride neocortex. However, there may be other factors at play, including the agerelated inability to restore molecular damage, or an accumulation of a variety of other ��lesions��, that result from the loss of, or increases in, a large number of Pentoxifylline adaptive brain processes present in most OO individuals surviving beyond the average life expectancy. Most individuals with dementia in our previous study were Braak stage V and VI, while those without dementia were classified as Braak stage III and IV. In addition, nondemented OO individuals exhibited a better brain perfusion preservation with lesser degrees of CAA and WMR compared to demented OO subjects. To complicate matters further, neuropathological examination of individuals diagnosed with dementia of the Alzheimer��s type revealed the presence of other concurrent neuropathological lesions that by themselves are sufficient to induce the symptoms of dementia, thus confounding clinical diagnoses as well as complicating the interpretation of clinical trial outcomes. The latest AD amyloidosis model is based on the assumption that Ab deposition follows a time-dependent sigmoidal kinetics with an asymptotic approach to saturation virtually coincident with the onset of dementia. The slope of the sigmoidal curve is likely to be variable since the deposition of amyloid in the cerebral cortex occurs at different rates and it is important to note that the early phases of the amyloid deposition processes are not well defined. It is clear that familial AD is characterized by Ab accumulation that starts at an early age, about the third and fourth decades of life, while in sporadic AD cases the deposition of amyloid begins about the fifth and sixth decades of life.