Selective effect of age, Apo e4, and Alzheimer's disease on hippocampal subfields - PubMed (original) (raw)

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

Susanne G Mueller et al. Hippocampus. 2009 Jun.

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.

2009 Wiley-Liss, Inc.

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Figures

FIGURE 1

FIGURE 1

(a) Parcellation scheme used for manual marking of subfields. As it is not possible to identify individual hippocampal layers at 4 T, the scheme was based on reliably recognizable anatomical landmarks even though this resulted in a part of the prosubiculum and subiculum proper being counted toward the CA1 sector. ERC, entorhinal cortex; CA1–2, CA1–CA2 transition zone (cf. methods in text); CA3&DG, CA3 and dentate gyrus. (b) Histological preparation of hippocampal subfields, arrow, dentate gyrus. (c) Typical example of hippocampal subfield markings. No. 1 is the most anterior slice, No. 5 the most posterior slice. No. 3 is referred to in the text as “starting” slice. Red, ERC; green, subiculum; blue, CA1; yellow, CA1–2 transition; maroon, CA3&DG.

FIGURE 2

FIGURE 2

(a) Age effect on CA1 in healthy controls. *, smaller (P < 0.05) compared to CA1 volume 3rd–5th decade; (b) Age effect on CA3-dentate in healthy controls. *, smaller (P < 0.05) compared to CA3&DG volume 3rd–4th decade. (c) Apo e4 effects in healthy controls (age range 22–85 yrs of age). Mean volumes and standard deviation (SD) of subjects without Apo e4 (bright blue), dark blue bars, mean volumes and SD of subjects with at least one Apo e4 allele (dark blue). *, smaller (P < 0.05) in Apo e4 carriers compared to non-Apo e4 carriers. (d) Mean volumes and SD of healthy, elderly controls (yellow), MCI (orange), and AD (red). *, smaller (P < 0.05) compared to corresponding volume in controls. (e) Apo E4 effect in AD. Mean volumes and SD of AD without Apo e4 (red) and with at least one Apo e4 allele (orange). *, smaller (P < 0.05) in Apo e4 carriers compared to non-Apo e4 carriers. (f) Apo E4 effect in MCI. Mean volumes and SD of MCI without Apo e4 (yellow) and MCI with at least one Apo e4 allele (bright yellow).

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