title: Atrophy and dysfunction of parahippocampal white matter in mild Alzheimer's disease.
abstract: In addition to atrophy of mesial temporal lobe structures critical for memory function, white matter projections to the hippocampus may be compromised in individuals with mild Alzheimer's disease (AD), thereby compounding the memory difficulty. In the present study, high-resolution structural imaging and diffusion tensor imaging techniques were used to examine microstructural alterations in the parahippocampal white matter (PWM) region that includes the perforant path. Results demonstrated white matter volume loss bilaterally in the PWM in patients with mild AD. In addition, the remaining white matter had significantly lower fractional anisotropy and higher mean diffusivity values. Both increased mean diffusivity and volume reduction in the PWM were associated with memory performance and ApoE ε4 allele status. These findings indicate that, in addition to partial disconnection of the hippocampus from incoming sensory information due to volume loss in PWM, microstructural alterations in remaining fibers may further degrade impulse transmission to the hippocampus and accentuate memory dysfunction. The results reported here also suggest that ApoE ε4 may exacerbate PWM changes.
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA. cwang30@emory.edu
authors.forename: Changsheng
authors.initials: C
authors.lastname: Wang
authors.forename: Glenn T
authors.initials: GT
authors.lastname: Stebbins
authors.forename: David A
authors.initials: DA
authors.lastname: Medina
authors.forename: Raj C
authors.initials: RC
authors.lastname: Shah
authors.forename: Roland
authors.initials: R
authors.lastname: Bammer
authors.forename: Michael E
authors.initials: ME
authors.lastname: Moseley
authors.forename: Leyla
authors.initials: L
authors.lastname: deToledo-Morrell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000473:pathology; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology* / Q000523:psychology; D016880:Anisotropy; D053327:Apolipoprotein E4 / Q000235:genetics; D001284:Atrophy; D003337:Corpus Callosum / Q000473:pathology*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D008568:Memory; D009413:Nerve Fibers, Myelinated / Q000473:pathology* / Q000502:physiology; D009435:Synaptic Transmission
chemical_list: D053327:Apolipoprotein E4