Hippocampal CA1 apical neuropil atrophy and memory performance in Alzheimer's disease

• Published in: NeuroImage (Orlando, Fla.) Vol. 63; no. 1; pp. 194 - 202
• Main Authors: Kerchner, Geoffrey A., Deutsch, Gayle K., Zeineh, Michael, Dougherty, Robert F., Saranathan, Manojkumar, Rutt, Brian K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.10.2012; Elsevier Limited
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - complications; Alzheimer Disease - pathology; Alzheimer Disease - physiopathology; Alzheimer's disease; Atrophy - pathology; Atrophy - physiopathology; Automation; CA1; Cognition & reasoning; Dementia; Female; Gender; Hippocampus; Hippocampus - pathology; Hippocampus - physiopathology; Humans; Magnetic Resonance Imaging; Male; Memory; Memory Disorders - etiology; Memory Disorders - pathology; Memory Disorders - physiopathology; Mental Recall; Middle Aged; Neuropil - pathology; Neuropsychology; NMR; Nuclear magnetic resonance; Older people; Recall; Structural imaging; Trends; Verbal learning; CA1; Magnetic resonance imaging; Memory; Neuropsychology; Alzheimer's disease; Hippocampus; Structural imaging; Dementia
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2012.06.048

Memory loss is often the first and most prominent symptom of Alzheimer's disease (AD), coinciding with the spread of neurofibrillary pathology from the entorhinal cortex (ERC) to the hippocampus. The apical dendrites of hippocampal CA1 pyramidal neurons, in the stratum radiatum/stratum lacunosum-moleculare (SRLM), are among the earliest targets of this pathology, and atrophy of the CA1-SRLM is apparent in postmortem tissue from patients with mild AD. We previously demonstrated that CA1-SRLM thinning is also apparent in vivo, using ultra-high field 7-Tesla (7T) MRI to obtain high-resolution hippocampal microstructural imaging. Here, we hypothesized that CA1-SRLM thickness would correlate with episodic memory performance among patients with mild AD. We scanned nine patients, using an oblique coronal T2-weighted sequence through the hippocampal body with an in-plane resolution of 220μm, allowing direct visual identification of subfields — dentate gyrus (DG)/CA3, CA2, CA1, and ERC — and hippocampal strata — SRLM and stratum pyramidale (SP). We present a novel semi-automated method of measuring stratal width that correlated well with manual measurements. We performed multi-domain neuropsychological evaluations that included three tests of episodic memory, yielding composite scores for immediate recall, delayed recall, and delayed recognition memory. Strong correlations occurred between delayed recall performance and the widths of CA1-SRLM (r2=0.69; p=0.005), CA1-SP (r2=0.5; p=0.034), and ERC (r2=0.62; p=0.012). The correlation between CA1-SRLM width and delayed recall lateralized to the left hemisphere. DG/CA3 size did not correlate significantly with any aspect of memory performance. These findings highlight a role for 7T hippocampal microstructural imaging in revealing focal structural pathology that correlates with the central cognitive feature of AD. ► 7T microstructural MRI reveals hippocampal subfields and stratal layers in vivo. ► CA1 apical neuropil atrophy correlated with memory deficits in Alzheimer's disease. ► This correlation was stronger in the left hemisphere. ► Entorhinal cortex and CA1 stratum pyramidale thicknesses also correlated with memory. ► CA1 apical neuropil atrophy may be useful as a biomarker to track memory loss in AD.