Atrophy is an extremely well established downstream effect of dementia due to Alzheimer’s Disease (AD). The hippocampus - a part of the brain associated with memory - is affected especially early in the disease course and the rate of atrophy is considerably higher for the hippocampus than for the brain as a whole. Changes in other regions of the brain including the amygdala, the parahippocampal gyrus and the lateral ventricles are also associated with dementia.


While the volume of research is greatest for AD, which is the most common dementia, atrophy of the hippocampus isn't just associated with AD. In frontal temporal dementia, the hippocampus often undergoes asymmetrical atrophy, and measuring this asymmetry can assist with the differential diagnosis. Measurement of amygdala volume can improve the quality of this differential diagnosis.


Measurement of hippocampal volume is used in other neurological disorders such as schizophrenia.

The Evidence Supporting Hippocampal Atrophy in Alzheimer's Disease

Measurement of hippocampal volume from structural MRI scans is a well-established biomarker correlating with disease stage1,2, cognitive performance3-6, post-mortem Braak stage7 and local neuronal density8. In the AD pathological cascade2, hippocampal atrophy accelerates before the transition to clinical dementia9.

Indeed, low hippocampal volume has been shown to be a predictive marker of AD in subjects with mild cognitive impairment (MCI)10-12. It is proposed as a screening criterion to select a more homogeneous prodromal patient population of increased risk for rapid imminent clinical progression13 and has recently been qualified by the European Medicines Agency (EMA) as a biomarker to enrich prodromal AD clinical trials14. Low hippocampal volume has also been proposed for new diagnostic criteria for MCI patients at high risk of converting to AD15.

1. Fox et al 2000
2. Jack et al 2000
3. Soininen et al 1994
4. van Petten 2004
5. Schuff et al 2009
6. Wolz et al 2010b
7. Braak and Braak 1991
8. Bobinski et al 1999
9. Jack et al 2011b
10. Convit et al 1997
11.Jack et al 1999
12.Gosche et al 2002
13. Hampel et al 2010
14. Hill et al 2013
15. Albert 2011