Selective effect of age, Apo e4, and Alzheimer's disease on hippocampal subfields

Abstract

Histopathological studies and animal models suggest that different physiological and pathophysiological processes exert different subfield specific effects on the hippocampus. High-resolution images at 4T depict details of the internal structure of the hippocampus allowing for in vivo volumetry of hippocampal subfields. The aims of this study were (1) to determine patterns of hippocampal subfield volume loss due to normal aging and Apo e4 carrier state, (2) to determine subfield specific volume losses due to preclinical (MCI) and clinical Alzheimer’s disease (AD) and their modification due to age and Apo e4 carrier state. One hundred fifty seven subjects (119 cognitively healthy elderly controls, 20 MCI and 18 AD) were studied with a high resolution T2 weighted imaging sequence obtained at 4T aimed at the hippocampus. Apo e4 carrier state was known in 95 subjects (66 controls, 14 MCI, 15 AD). Subiculum (SUB), CA1, CA1–CA2 transition zone (CA1–2 transition), CA3- dentate gyrus (CA3&DG) were manually marked. Multiple linear regression analysis was used to test for effects of age, Apo e4 carrier state and effects of MCI and AD on different hippocampal subfields. Age had a significant negative effect on CA1 and CA3&DG volumes in controls (P < 0.05). AD had significantly smaller volumes of SUB, CA1, CA1–2 transition, and MCI had smaller CA1–2 transition volumes than controls (P < 0.05). Apo e4 carrier state was associated with volume loss in CA3&DG compared to non-Apo e4 carriers in healthy controls and AD. Based on these findings, we conclude that subfield volumetry provides regional selective information that allows to distinguish between different normal and pathological processes affecting the hippocampus and thus for an improved differential diagnosis of neurodegenerative diseases affecting the hippocampus.

Automated Segmentation of Hippocampal Subfields in Drug-Naïve Patients with Alzheimer Disease

“…To date, there was a study on the hippocampal subfield volume segmentation analysis in AD. 5 Using manual segmentation analysis of hippocampal subfield volume, Mueller and Weiner 5 reported that patients with AD had smaller subicular and CA1 volumes, compared with controls, which is in line with those in our study. In the progression from mid cognitive impairment to AD, neurodegeneration is known to occur in a progressive and hierarchic fashion.…”

“…22 In addition, the left total hippocampal and CA4-DG volumes were negatively correlated significantly with age in the control group, which was also in accordance with those in the previous studies. 5,6 The study by Hanseeuw et al 6 showed that total hippocampal volume was significantly explained by age in the healthy elderly controls. Additionally, they showed that age tended to explain CA4-DG volume in the controls.…”

“…6 However, these results were not in line with those in previous studies using the manual segmentation of hippocampal subfields or 3D surface mapping of the hippocampus. 5,22 As to this discrepancy, Hanseeuw et al suggested that there was a boundary difference between the studies and possible CA1 hypertrophy in aMCI. They also suggested that the reproducibility of their method would permit more consistency between studies than was possible with manual methods.…”

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

“…Manual methods to determine hippocampal subfields are based on the direct identification of anatomical boundaries and serve as goldstandard to assess the performance of automated methods. Using hippocampus subfields can significantly decrease the rate of false positive findings in the prediction of future conversion from MCI to AD using manual [168] or automated [169] measurement. Sequences at 7 Tesla provide higher spatial resolution, new contrasts and access to even finer substructures of the hippocampus [170,171], but the clinical relevance of these measures needs to be explored in future studies [172].…”

Cytoprotective effects of growth factors: BDNF more potent than GDNF in an organotypic culture model of Parkinson's disease

“…Differential susceptibility of specific subsets of neurons within a region is not a unique feature for the midbrain. Hippocampal CA1 neurons are more vulnerable than CA3 neurons to a variety of adverse conditions, including global cerebral ischemia, toxins, chronic epileptic seizures, aging, oxidative stress and early stages of AD (418)(419)(420)(421). Thus, similar neuronal populations with regional proximity may have unique vulnerability profiles.…”