RI scans, suggesting that some of the age-related cognitive decline may be explained by greater white matter hyperintensities. De Groot et ai82 examined the association between periventricular and subcortical white matter hyperintensities and cognitive deficits in more than 1000 community-dwelling Fostamatinib mw healthy individuals. After adjusting for atrophy, Inhibitors,research,lifescience,medical stroke history, educational level, and presence of depression, they found a significant association between neuropsychological

deficits (primarily psychomotor speed) and periventricular, but not subcortical, white matter hyperintensities. Inzitari ct al83 suggested that, a direct, effect of white matter hyperintensities on cognition may be explained by disconnection between cortical and subcortical brain regions due to fiber tract, demyelination and gliosis. Schretlen et al24 assessed a group of 112 healthy young and old adults with high-resolution Inhibitors,research,lifescience,medical MRI and tasks of perceptual comparison speed, working memory, and executive functions. One of their main findings was that. both age and executive abilities had a significant correlation with frontal lobe volume (ie,

older age and more deficits on executive functions were significantly Inhibitors,research,lifescience,medical related to smaller frontal lobes). A similar correlation between more perseverations on a set-shifting task and smaller frontal lobe volumes was reported by Raz et al.71 Several studies tried to disentangle the neuropathologic changes specific to AD from those related to the aging process. Brains of elderly cognitivcly normal individuals may show the initial changes of AD, such as senile plaques, neurofibrillary tangles, Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical and Lewy bodies, albeit, below the amount required

to make a pathologic diagnosis of a specific neuropathologic condition.84 These changes were considered as either part, of the normal aging process, or as incipient, AD.85 In a sample of 10 brains from, cognitively normal individuals aged 85 to 105 years at time of death, Hulcttc et al86 found a relatively poorer cognitive performance in tasks of memory and executive functions in those individuals with the neuropath ological changes of early AD compared with individuals with normal brains. This lack of brain pathological changes Electron transport chain in a subgroup of elderly individuals demonstrates that AD is not a final common pathway for the oldest-old. In conclusion, age-related volume reductions were reported mainly for the frontal lobes and limbic regions. This process is not linear, but may occur at specific stages of life. White matter hyperintensities are related to older age and may explain some of the age-related cognitive decline. The early ncuropathological changes of AD may account for mild cognitive deficits in nondemented elderly individuals.