Neuropathologic Substrate of Mild Cognitive Impairment

Abstract

To define the neuropathologic findings in amnestic mild cognitive impairment (MCI) and early Alzheimer disease (EAD). Methods: The mean numbers of diffuse plaques, neuritic plaques (NPs), and neurofibrillary tangles (NFTs) in 4 neocortical regions and 4 ventromedial temporal lobe regions were counted in 10 patients with amnestic MCI and compared with the mean numbers in 23 normal control subjects and 10 patients with EAD, and then were compared with memory performance. All of the controls and patients were followed longitudinally. Results: Patients with MCI showed no significant difference (PϾ.05) in the number of diffuse plaques from that in normal controls or patients with EAD. In patients with MCI, the number of NPs was significantly elevated in all 4 neocortical regions and amygdala compared with controls (PϽ.01 to Ͻ.001). There were no significant differences (PϾ.05) in the number of NPs between MCI and EAD cerebral cortex, but significant increases were present for NPs in EAD amygdala and subiculum compared with MCI (PϽ.01). In patients with MCI compared with controls, the only significant increase in NFTs in the neocortex was in the parietal lobe. However, the number of NFTs was significantly elevated in MCI in all 4 ventromedial temporal lobe structures compared with controls (PϽ.01 to Ͻ.001). In comparing MCI with EAD, there were significant increases in NFTs in EAD in frontal and temporal lobes, amygdala, and subiculum (PϽ.01). The numbers of NPs and NFTs were significantly elevated in all of the neocortical regions and ventromedial temporal lobe regions in patients with EAD compared with controls (PϽ.001). Memory function was significantly correlated with NFTs in CA1 of the hippocampus (PϽ.01) and the entorhinal cortex (PϽ.05). Conclusions: In patients with amnestic MCI who were followed longitudinally, the early changes of Alzheimer disease were present. The NFTs were slightly more prominent than ␤-amyloid peptide deposition in the progression from normal to MCI to EAD. Ventromedial temporal lobe NFTs probably represent the substrate for memory decline in MCI. From a neuropathologic perspective, it appears that amnestic MCI is, in reality, EAD.

Multicentre variability of MRI-based medial temporal lobe volumetry in Alzheimer's disease

“…There is some, but still very limited, evidence that neuron loss may be more pronounced and neurofibrillary tangles may be more frequent in amygdala than in hippocampus in early stages of AD [2,20,33,34,43,47,52]. This may indicate more rapid progression or earlier onset of pathological changes in amygdala than hippocampus so that amygdala atrophy may have reached its maximum even before the conversion from MCI to AD.…”

Captopril and Valsartan May Improve Cognitive Function Through Potentiation of the Brain Antioxidant Defense System and Attenuation of Oxidative/Nitrosative Damage in STZ-Induced Dementia in Rat

“…According to recent studies, the beginning of AD is generally preceded by an temporary phase known as MCI, when there is no significant increase in the senile Advanced Pharmaceutical Bulletin, 2016, 6(4), 531-539 plaques and neurofibrillary tangles. 14,41 These subjects exhibit a significant oxidative imbalance. 8,9,14 The findings of present study indicated that using captopril and valsartan during AD has attenuated the free radicals production of ROS and RNS, (Figures 5 and 6).…”

Neurological Factors in Cognitive Aging

“…In persons with mild cognitive impairment proximate to death, levels of Alzheimer's disease pathology Petersen et al, 2006) and cerebral infarction have been shown to be intermediate between levels in persons with no cognitive impairment and those with dementia. Neurofibrillary pathology in particular has been proposed as the pathologic substrate of mild cognitive impairment (Guillozet, Weintraub, Mash, & Mesulam, 2003;Riley, Snowden, & Markesbery, 2002) and, from a neuropathologic standpoint, mild cognitive impairment has been characterized as early Alzheimer's disease (Markesbery et al, 2006). Neither is the impact of age-related neuropathology confined to persons with mild cognitive impairment.…”