Asymmetrical Volume Loss in Hippocampal Subfield During the Early Stages of Alzheimer Disease: A Cross Sectional Study

다국어 초록 (Multilingual Abstract)

Hippocampal atrophy is a well-established imaging biomarker of Alzheimer disease (AD). However, hippocampus is a non-homogenous structure with cytoarchitecturally and functionally distinct sub-regions or subfield, with each region performing distinct functions. Certain regions of the subfield have shown selective vulnerability to AD. Here, we are interested in studying the effects of normal aging and mild cognitive impairment on these sub-regional volumes. With a reliable automated segmentation technique, we segmented these subregions of the hippocampus in 101 cognitively normal (CN), 135 early mild cognitive impairment (EMCI), 67 late mild cognitive impairment (LMCI) and 48 AD subjects. Thereby, dividing the hippocampus into hippocampal tail (tail), subiculum (SUB), cornu ammonis 1 (CA1), hippocampal fissure (fissure), presubiculum (PSUB), parasubiculum (ParaSUB), molecular layer (ML), granule cells/molecular layer/dentate gyrus (GCMLDG), cornu ammonis 3(CA3), cornu ammonis 4(CA4), fimbria and hippocampal-amygdala transition area (HATA). In this cross sectional study of 351 ADNI subjects, no differences in terms of age, gender, and years of education were observed among the groups. Though, the groups had statistically significant differences (p < 0.05 after the multiple comparison correction) in the Mini-Mental State Examination (MMSE) scores. There was asymmetrical volume loss in the early stages of AD with the left hemisphere showing volume loss in regions that were unaffected in the right hemisphere. Bilateral parasubiculum, right cornu ammonis 1, 3 and 4, right fimbria and right HATA regions did not show any volume loss till the late MCI stages. Our findings suggest that the hippocampal subfield regions are selectively vulnerable to AD and also that these vulnerabilities are asymmetrical especially during the early stages of AD.

참고문헌 (Reference)

1 Simic G, "Volume and number of neurons of the human hippocampal formation in normal aging and Alzheimer's disease" 379 (379): 482-494, 1997

2 Bernard C, "Time course of brain volume changes in the preclinical phase of Alzheimer’s disease" 10 (10): 143-151, 2014

3 O'Mara S, "The subiculum: what it does, what it might do, and what neuroanatomy has yet to tell us" 207 (207): 271-282, 2005

4 Duvernoy HM, "The human hippocampus : functional anatomy, vascularization, and serial sections with MRI" Springer 2005

5 McKhann GM, "The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease" 7 (7): 263-269, 2011

6 Jack CR Jr., "The Alzheimer's Disease Neuroimaging Initiative (ADNI): MRI methods" 27 (27): 685-691, 2008

7 Smith CD, "Structural Brain Alterations before Mild Cognitive Impairment in ADNI: Validation of Volume Loss in a Predefined Antero-Temporal Region" 31 (31): 49-58, 2012

8 Lucassen P, "Stress, Depression and Hippocampal Apoptosis"

9 Mueller SG, "Selective effect of age, Apo e4, and Alzheimer’s disease on hippocampal subfields" 19 (19): 558-564, 2009

10 Dale AM, "Segmentation and Surface Reconstruction" 9 (9): 179-194, 1999

11 Jack CR, "Rates of ${\beta}$-amyloid accumulation are independent of hippocampal neurodegeneration" 82 (82): 1605-, 2014

12 Loewenstein DA, "Predominant left hemisphere metabolic dysfunction in dementia" 46 (46): 146-152, 1989

13 Braak H, "Neuropathological stageing of Alzheimer-related changes" 82 (82): 239-259, 1991

14 Adachi M, "Morphology of the inner structure of the hippocampal formation in Alzheimer disease" 24 (24): 1575-1581, 2003

15 Petersen RC, "Mild cognitive impairment as a diagnostic entity" 256 (256): 183-194, 2004

16 Toga AW, "Mapping brain asymmetry" 4 : 37-, 2003

17 Devanand DP, "MRI hippocampal and entorhinal cortex mapping in predicting conversion to Alzheimer’s disease" 60 (60): 1622-1629, 2012

18 Leow AD, "Longitudinal stability of MRI for mapping brain change using tensor-based morphometry" 31 (31): 627-640, 2006

19 Leutgeb S, "Independent codes for spatial and episodic memory in hippocampal neuronal ensembles" 309 (309): 619-623, 2005

20 Mueller SG, "Hippocampal atrophy patterns in mild cognitive impairment and Alzheimer's disease" 31 (31): 1339-1347, 2010

21 Hou G, "Hippocampal asymmetry: differences in structures and functions" 38 (38): 453-460, 2013

22 Kerchner GA, "Hippocampal CA1 apical neuropil atrophy and memory performance in Alzheimer's disease" 63 (63): 194-202, 2012

23 Massman PJ, "Hemispheric asymmetry in Alzheimer's disease is apparent in motor functioning" 18 (18): 110-121, 1996

24 Zahn R, "Hemispheric asymmetries of hypometabolism associated with semantic memory impairment in Alzheimer's disease: a study using positron emission tomography with fluorodeoxyglucose-F18" 132 (132): 159-172, 2004

25 Wang L, "Fully-automated, multi-stage hippocampus mapping in very mild Alzheimer disease" 19 (19): 541-548, 2009

26 Thompson PM, "Dynamics of gray matter loss in Alzheimer's disease" 23 (23): 994-1005, 2003

27 Lee I, "Differential contributions of dorsal hippocampal subregions to memory acquisition and retrieval in contextual fear-conditioning" 14 (14): 301-310, 2004

28 Mak E, "Differential Atrophy of Hippocampal Subfields: A Comparative Study of Dementia with Lewy Bodies and Alzheimer Disease" 24 (24): 136-143, 2016

29 West MJ, "Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer’s disease" 344 (344): 769-772, 1994

30 Fischl B, "Cortical Surface-Based Analysis: II: Inflation, Flattening, and a Surface-Based Coordinate System" 9 (9): 195-207, 1999

31 Chow N, "Comparing Hippocampal Atrophy in Alzheimer’s Dementia and Dementia with Lewy Bodies" 34 (34): 44-50, 2012

32 McKhann G, "Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease" 34 (34): 939-944, 1984

33 Smith CD, "Brain structural alterations before mild cognitive impairment" 68 (68): 1268-1273, 2007

34 Pedraza O, "Asymmetry of the hippocampus and amygdala in MRI volumetric measurements of normal adults" 10 (10): 664-678, 2004

35 Bugiani O, "Asymmetrical cerebral atrophy in Alzheimer’s disease" 10 (10): 55-60, 1991

36 "Amyloid deposition, hypometabolism, and longitudinal cognitive decline" 72 (72): 578-586, 2012

37 Braak E, "Alzheimer’s disease: Transiently developing dendritic changes in pyramidal cells of sector CA1 of the Ammon’s horn" 93 : 323-325, 1997

38 Iglesias JE, "A computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI: Application to adaptive segmentation of in vivo MRI" 115 : 117-137, 2015

39 Fletcher E, "${\beta}$-amyloid, hippocampal atrophy and their relation to longitudinal brain change in cognitively normal individuals" 40 : 173-180, 2016

40 "2018 Alzheimer's disease facts and figures" 14 (14): 367-429, 2018