Distinct neuroanatomical bases of episodic and semantic memory performance in Alzheimer’s disease

Abstract

Alzheimer's disease (AD) neurofibrillary pathology begins in the medial perirhinal cortex (mPRC) before spreading to the entorhinal cortex (ERC) and hippocampus (HP) in anterior medial temporal lobe (aMTL). While the role of the ERC/HP complex in episodic memory formation is well-established, recent research suggests that the PRC is required to form semantic memories of individual objects. We aimed to test whether commonly used clinical measures of episodic and semantic memory are distinctly associated with ERC/HP and mPRC integrity, respectively, in healthy mature individuals and very early AD patients. One hundred thirty normal controls, 32 amnestic mild cognitive impairment patients, some of whom are in the earliest (i.e., preclinical) stages of AD, and ten early-stage AD patients received neuropsychological testing and high-resolution anatomic and diffusion MRI. Voxel-based regression analyses tested for regions where episodic memory (delayed recall scores on the California Verbal Learning and Rey Osterrieth Complex Figure Tests) and semantic memory (Boston Naming Test, category fluency) performance correlated with gray matter (GM) regions of interest and whole-brain fractional anisotropy (FA) voxel values. When controlling for the opposing memory performance, poorer episodic memory performance was associated with reduced bilateral ERC/HP GM volume and related white matter integrity, but not with mPRC GM volume. Poor semantic memory performance was associated with both reduced left mPRC and ERC/HP GM volume, as well as reduced FA values in white matter tracts leading to the PRC. These results indicate a partial division of labor within the aMTL and suggest that mPRC damage in very early AD may be detectable with common clinical tests of semantic memory if episodic memory performance is controlled.

Neuropsychological Markers of Medial Perirhinal and Entorhinal Cortex Functioning are Impaired Twelve Years Preceding Diagnosis of Alzheimer’s Dementia

“…Similar findings were reported by Wilson et al [42], who showed that an average of three semantic memory tests (i.e., verbal fluency, Boston Naming Test, and a measure of reading recognition) was affected earlier than episodic memory performance (76 versus 63 months, respectively) in a group of 462 NC-AD patients. Since the mPRC presumably codes for semantic object memories [14,16], the findings of Amieva et al [32] and Wilson et al [42] are in line with the pattern of cortical NFT pathology in AD, which affects the mPRC before the ERC in the preclinical course of AD [5].…”

“…However, many wellestablished clinical neuropsychological tests used in current longitudinal studies are more meta-cognitive in nature, lacking the anatomical specificity to target the PRC. For example, Hirni et al [16] demonstrated that both clinical tests of episodic memory and semantic object memory significantly predicted ERC/HP and PRC atrophy. However, linear regression analyses differentiated the relationships between PRC integrity and semantic memory functioning, and ERC/HP integrity and episodic memory functioning: when the opposing memory performance was controlled, episodic memory performance was associated with ERC/HP but not PRC integrity, whereas semantic memory was associated with both PRC and ERC/HP integrity [16].…”

“…For example, Hirni et al [16] demonstrated that both clinical tests of episodic memory and semantic object memory significantly predicted ERC/HP and PRC atrophy. However, linear regression analyses differentiated the relationships between PRC integrity and semantic memory functioning, and ERC/HP integrity and episodic memory functioning: when the opposing memory performance was controlled, episodic memory performance was associated with ERC/HP but not PRC integrity, whereas semantic memory was associated with both PRC and ERC/HP integrity [16]. These results indicate that when existing clinical neuropsychological data are used to assess PRC and ERC/HP functions, one way to increase anatomical specificity for medial temporal lobe substructures would be to control for the opposing memory performance.…”

Brain Volume, Connectivity, and Neuropsychological Performance in Mild Traumatic Brain Injury: The Impact of Post-Traumatic Stress Disorder Symptoms

“…Prior studies suggest the involvement of the EC in learning and memory. [31][32][33] The EC serves as a gateway between the hippocampus and frontal aspects of the neocortex, playing a central role in memory retrieval. 31 In our sample of mTBI/PTSD subjects, the EC was unexpectedly found to be enlarged, compared with mTBIonly subjects.…”

Transorbital endoscopic amygdalohippocampectomy: a feasibility investigation

“…34 Additional evidence for the role of the lateral cortex in working memory is the higher rate of memory decline following anterior temporal lobectomy compared with selective amygdalohippocampectomy. 18 The perirhinal cortex and temporal lobe white matter tracts are involved in semantic memory processing, 23 as are the middle and inferior temporal gyri. 9 Traditional surgical approaches can compromise the cortex and fiber tracts subserving memory function, resulting in progressive white matter atrophy up to a year following surgery 16 and impeding cognitive recovery.…”