Medial temporal lobe atrophy is the norm in cerebrovascular dementias

Brain imaging has become an important tool to define atrophy related to neurodegenerative and vascular processes, which determine cognitive decline and dementia. Longitudinal studies suggest that rates of atrophy increase in a number of medial temporal lobe structures including the subfields of the hippocampus and the entorhinal cortices in non-demented ageing individuals. The mean annual rate of hippocampal volume loss is estimated to be 1.6%–2.0% per year after 70 years of age. These rates are determined to be 2.5 times greater in Alzheimer’s disease (AD) [1]. Incorporating the hippocampal formation, medial temporal lobe atrophy (MTLA) is widely regarded as a key biomarker of AD. However, MTLA and hippocampal atrophy have been described to be associated with other types of neurocognitive disorders including dementia with Lewy bodies, vascular dementia and post-stroke dementia (PSD). In recent years, our attention has been drawn to the association of MTLA with cognitive impairment related to different vascular conditions including transient ischaemic attack, first-episode stroke, cerebral small vessel disease (SVD) and carotid artery disease. Increasing severity of MTLA has been associated with amnestic vascular cognitive impairment no dementia (odds ratio 2.7) compared to non-amnestic vascular cognitive impairment no dementia in post-stroke survivors. MTLA is also associated with slowing psychomotor speed and declining executive functions in SVD and with a shorter time to delayed dementia after stroke [2]. Hippocampal volumes could be reduced by as much as 15% in subcortical vascular dementia relative to normal ageing controls. These findings are complemented by similar reductions in blood flow in the posterior cerebral artery territories and in hippocampal volumes in both PSD and AD subjects. All these observations reinforce the notion that MTLA (odds ratio 1.3–6.14) is a mainstay and appears to be an independent change in most cerebrovascular disease associated with cognitive impairment. It is reasoned that an ongoing concomitant neurodegenerative process causes MTLA in the preclinical phase at the time of stroke occurrence and before the development of dementia. Contamination with AD or other neurodegenerative pathology as a possible cause of MTLA or hippocampal atrophy has been worrisome to the most careful investigators. They interpret their observations with the idea that there is a greater role for Alzheimer-type pathology than cerebrovascular lesions in the development of cognitive impairment after onset of clinical stroke. In this issue, Arba and colleagues [3] explored the relationship between radiological features suggestive of AD and SVD as defined radiologically by the presence of white matter hyperintensities and other features per STRIVE (for Standards for Reporting Vascular Changes on Neuroimaging). They assessed the association of each of these features with cognitive status at 1 year in patients with stroke or transient ischaemic attack recruited in the Virtual International Stroke Trials Archive (VISTA). Interestingly, moderate to severe MTLA was present in 44% of patients and SVD features were independently associated with MTLA. Whilst comprehensive neuropsychometric assessment was not possible, MTLA was the only radiological feature independently associated with worsening cognitive impairment as measured by the Mini Mental State Examination. Why is an alternative view not plausible that AD pathology makes little if any contribution in SVD or post-stroke related cognitive impairment? Recent studies involving first-time stroke subjects suggested that MTLA was associated with greater neuropsychiatric symptoms [4] but excitingly also in the absence of AD pathology as determined by Pittsburgh compound B binding to track amyloid burden [4]. This is consistent with the observation that more than 75% of poststroke survivors who developed PSD and exhibited MTLA met pathological criteria for vascular dementia [5]. Perhaps the strongest evidence for a vascular basis for MTLA or hippocampal atrophy comes from genetic and animal models of SVD. For example, in CADASIL (for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) subjects hippocampal volumes were reduced in dementia in the whole cohort and in a subgroup progressing to dementia before age 60 years [6]. Animal models of long-term hypoperfusion show that coexisting neurodegenerative changes are not a prerequisite for hippocampal atrophy [7]. These findings strengthen the view that hippocampal atrophy and