Presymptomatic hippocampal atrophy in Alzheimer's disease: A longitudinal MRI study
Abstract
The hippocampal formation (HF) is known from pathological and MRI studies to be severely atrophied in established Alzheimer's disease. However, it is unclear when the earliest changes in the HF occur. We performed a longitudinal study of asymptomatic individuals at risk of autosomal dominant familial Alzheimer's disease in order to assess presymptomatic changes in the HF. Seven at risk members of a familial Alzheimer's disease pedigree associated with the amyloid precursor protein 717 valine to glycine mutation underwent serial MR scanning and neuropsychological assessments over 3 years. These assessments were compared with results from 38 normal controls. During the study three at risk subjects became clinically affected. Volumetric measurement of the HF showed that asymmetrical atrophy developed in these subjects before the appearance of symptoms. Verbal and visual memory measures declined in parallel with hippocampal loss. A loss of up to 8% per annum of the volume of the HF occurred in the 2 years over which symptoms first appeared. These findings may have implications for early diagnosis of Alzheimer's disease.
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This rate was also within the range described in another study (27) using MRI volumetrics, but less than described by a different group (28) who measured the change in thickness of the medial temporal lobe on CT.
“This rate was also within the range described in another study (27) using MRI volumetrics, but less than described by a different group (28) who measured the change in thickness of the medial temporal lobe on CT.”
From Rates of hippocampal atrophy correlate with change in clinical status in aging and AD (2000) · cites this paper as [27]
Other groups have also shown that assessments of hippocampal atrophy can provide predictive information in patients who are at elevated risk for AD (27, 30).
“Other groups have also shown that assessments of hippocampal atrophy can provide predictive information in patients who are at elevated risk for AD(27, 30).”
From Rates of hippocampal atrophy correlate with change in clinical status in aging and AD (2000) · cites this paper as [27]
Brain structures critical to episodic remembering, such as the hippocampus and neighboring regions, show pathological alterations long before clinical diagnosis of Alzheimer's disease.
“These observations are consistent with findings that brain structures known to be critical to episodic remembering, such as the hippocampus and neighboring regions (Nyberg, McIntosh, Houle, Nilsson, & Tulving, 1996; Vargha-Khadem et al., 1997), show pathological alterations long before clinical diagnosis (Braak & Braak, 1995; Fox et al., 1996; S. A. Small, Perara, DeLaPaz, Mayeux, & Stern, 1999).”
From Cognitive impairment in preclinical Alzheimer's disease: a meta-analysis (2005) · cites this paper as Fox et al., 1996
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- Authors
- Fox, N. C., Warrington, E. K., Freeborough, P. A., Hartikainen, P., Kennedy, A. M., Stevens, J. M., & Rossor, M. N.
- Affiliations
- St Mary's Hospital (GB)
- National Hospital for Neurology and Neurosurgery (GB)
- Corresponding author
- Rossor, M. N.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 1996
- Volume
- 119
- Issue
- 6
- Pages
- 2001-2007
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2015629132
- Cited by
- 656
- References
- 30
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 12 · 2023: 21 · 2022: 18 · 2021: 21 · 2020: 32 · 2019: 19 · 2018: 26 · 2017: 18 · 2016: 26 · 2015: 29 · 2014: 13 · 2013: 33 · 2012: 22
- FWCI
- 9.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- Alzheimer's disease, familial Alzheimer's disease, amyloid precursor protein mutations, hippocampal volume, memory decline, early diagnosis, longitudinal MRI
- MeSH terms
- Aged, Alzheimer Disease, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Amyloid beta-Protein Precursor
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