Abstract
The severe cognitive deficits in Alzheimer disease are associated with structural lesions in gray and white matter in addition to changes in synaptic function. The current investigation studied the breakdown of the structure and function in regional networks involving the Papez circuit and extended neocortical association areas. Cortical volumetric and diffusion tensor imaging (3T MR imaging), positron-emission tomography with (18)F fluorodeoxyglucose on a high-resolution research tomograph, and comprehensive neuropsychological assessments were performed in patients with late-onset sporadic Alzheimer disease, those with mild cognitive impairment, and elderly healthy controls. Atrophy of the medial temporal lobes was the strongest and most consistent abnormality in patients with mild cognitive impairment and Alzheimer disease. Atrophy in the temporal, frontal, and parietal regions was most strongly related to episodic memory deficits, while deficits in semantic cognition were also strongly related to reductions of glucose metabolism in the posterior cingulate cortex and temporoparietal regions. Changes in fractional anisotropy within white matter tracts, particularly in the left cingulum bundle, uncinate fasciculus, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus, were significantly associated with the cognitive deficits in multiple regression analyses. Posterior cingulate and orbitofrontal metabolic deficits appeared to be related to microstructural changes in projecting white matter tracts. Many lesioned network components within the Papez circuit and extended neocortical association areas were significantly associated with cognitive dysfunction in both mild cognitive impairment and late-onset sporadic Alzheimer disease. Hippocampal atrophy was the most prominent lesion, with associated impairment of the uncinate and cingulum white matter microstructures and hippocampal and posterior cingulate metabolic impairment.
Highlights
MethodsCortical volumetric and diffusion tensor imaging (3T MR imaging), positron-emission tomography with 18F fluorodeoxyglucose on a high-resolution research tomograph, and comprehensive neuropsychological assessments were performed in patients with late-onset sporadic Alzheimer disease, those with mild cognitive impairment, and elderly healthy controls
BACKGROUND AND PURPOSEThe severe cognitive deficits in Alzheimer disease are associated with structural lesions in gray and white matter in addition to changes in synaptic function
Many lesioned network components within the Papez circuit and extended neocortical association areas were significantly associated with cognitive dysfunction in both mild cognitive impairment and late-onset sporadic Alzheimer disease
Summary
Cortical volumetric and diffusion tensor imaging (3T MR imaging), positron-emission tomography with 18F fluorodeoxyglucose on a high-resolution research tomograph, and comprehensive neuropsychological assessments were performed in patients with late-onset sporadic Alzheimer disease, those with mild cognitive impairment, and elderly healthy controls. Age (yr) Sex (M/F) Years of education MMSE score APOE ⑀4 TIV (cm3) Total ACE-R ACE-R Memory Category Fluency ACE-R Attention Mean 3:8. Note:—HC indicates healthy controls; APOE ⑀4 indicates the number of participants carrying at least 1 ⑀4 allele (APOE data were unavailable from 1 healthy control and 3 patients with MCI); MMSE, Mini-Mental State Examination; TIV, total intracranial volume. There was a significant group difference for age, F(2, 27) ϭ 4.5, P Ͻ .05; MMSE score, F(2, 27) ϭ 20.2, P Ͻ .001; total ACE-R, F(2, 27) ϭ 29.9, P Ͻ .001; ACE-R Memory, F(2, 27) ϭ 42.2, P Ͻ .001; Category Fluency, F(2, 27) ϭ 20.1, P Ͻ .001; ACE-R Attention, F(2, 27) ϭ 11.4, P Ͻ .001. There was a significant group difference for age, F(2, 27) ϭ 4.5, P Ͻ .05; MMSE score, F(2, 27) ϭ 20.2, P Ͻ .001; total ACE-R, F(2, 27) ϭ 29.9, P Ͻ .001; ACE-R Memory, F(2, 27) ϭ 42.2, P Ͻ .001; Category Fluency, F(2, 27) ϭ 20.1, P Ͻ .001; ACE-R Attention, F(2, 27) ϭ 11.4, P Ͻ .001. b Significantly different from AD. c Significantly different from HC. d Significantly different from MCI
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