In addition, age, the most significant risk factor for dementia, also plays a role in the extent of ADassociated neuropathology observed in the brain, irrespective of the presence or absence of dementia symptoms. Thus, if questions regarding the presence, absence, or extent of neuropathologic lesions or Ruxolitinib in vivo neurobiological Inhibitors,research,lifescience,medical changes are framed in the context of whether persons with MCI meet neuropathological criteria for AD, the results may lead to very different conclusions than if the questions are framed within the context of whether persons with MCI present with lesion densities or neurobiological changes that are different from those without cognitive impairments. In general,

Inhibitors,research,lifescience,medical the brains of persons with MCI do not meet neuropathological criteria for AD, but they nevertheless evidence pathological features that are qualitatively, but not quantitatively, AD-like (please see below). An illustrative example is a study of the association of neuritic plaques with cognitive compromise as defined by the CDR.35 Persons with no cognitive impairment were compared with those with different levels of impairment. Persons with CDRs of 0.5 (ie, MCI), had cortical neuritic plaque densities that were significantly higher than that of persons with intact Inhibitors,research,lifescience,medical cognition. Yet, the majority

of the studied sample with CDR scores of 0.5 and even those with CDR scores of 1 did not meet accepted neuropathological criteria lor AD.31,32,36 Similar results Inhibitors,research,lifescience,medical have been reported using different MCI classification schemes and different metrics of AD-associated lesion densities

(eg, ref 37). General neuropathology The majority of the studies of the neuropathology Inhibitors,research,lifescience,medical of MCI, especially degenerative/amnestic MCI,11,12 suggest that in most instances MCI is associated with a less fervent manifestation of the neuropathologies that are generally associated with dementia. Unselected MCI samples derived from memory clinic or general geriatric populations evidence a variety of neuropathologic lesions such as those associated with diffuse Lewy body disease, cerebrovascular disease, ischemic changes and hippocampal sclerosis, argtrophilic grain disease, Parkinson’s disease, and, of course, AD (eg, refs 37-40). Nearly invariably, the extent of these lesions is considerably 17-DMAG (Alvespimycin) HCl less than those observed in persons with frank dementia. In general, relative to persons with intact cognition, the frequency of AD-associated neuropathology in persons with MCI, especially those with amnestic MCI, is significantly greater than other neuropathologic lesions associated with dementia.40,41 Hallmark lesions of AD Alzheimer’s disease is characterized by extracellular neuritic plaques (NP) and intracellular neurofibrillary tangles (NFT).