Histological validation of calcifications in the human hippocampus as seen on computed tomography.

BACKGROUND: Calcifications within the hippocampus were recently described for the first time on computed tomography (CT). These calcifications appeared in patients older than 50 years, the prevalence increases with age and they may be associated with cognitive decline. The aim of this study was to determine the histological basis (the presence, severity and location) of these CT-detected hippocampal calcifications of post-mortem brains. METHODS: CT scans of seven post-mortem brains were scored for the presence and severity (mild, moderate, severe) of hippocampal calcification. After this, samples from nine hippocampi (bilateral in two brains, unilateral in five brains) were stained with hematoxylin and eosin (HE) to indicate the cytoarchitecture, with Elastica van Gieson to analyse the elastic connective tissue of the vessel walls and with von Kossa for detection of calcium. RESULTS: In four brains (six hippocampi), calcifications were both found on CT and in corresponding histology. In three brains (three hippocampi), calcifications were absent on CT and corresponding histology. In histology, mild calcifications were located in the tail and severe calcifications involved the tail, body and sometimes the head of the hippocampus. The calcifications co-localised with precapillaries, capillaries and arteries of the molecular and granular layers of the dentate gyrus and the Cornu Ammonis 1. CONCLUSIONS: In this study, calcifications of the hippocampus as seen on CT scans were histologically located in vascular structures of the tail, body and head of the hippocampus.

Hippocampal calcification on brain CT: prevalence and risk factors in a cerebrovascular cohort.

OBJECTIVES: Recently, hippocampal calcification as observed on brain CT examinations was identified in over 20% of people over 50 years of age and a relation between hippocampal calcification and cognitive decline was shown. We determined the prevalence and investigated the vascular risk factors of hippocampal calcification in patients with cerebrovascular disease. METHODS: Hippocampal calcification was scored bilaterally on presence and severity on CT examinations in a cohort of 1130 patients with (suspected) acute ischaemic stroke. Multivariable logistic regression analysis, adjusting for age and gender as well as adjusting for multiple cardiovascular disease risk factors, was used to determine risk factors for hippocampal calcification. RESULTS: Hippocampal calcification was present in 381 (34%) patients. Prevalence increased with age from 8% below 40 to 45% at 80 years and older. In multivariable logistic regression analysis, age per decile (OR 1.41 [95% CI 1.26-1.57], p < 0.01), hypertension (OR 0.74 [95% CI 0.56-0.99], p = 0.049), diabetes mellitus (OR 1.57 [95% CI 1.10-2.25], p = 0.01) and hyperlipidaemia (OR 1.63 [95% CI 1.20-2.22], p < 0.01) were significantly associated with hippocampal calcification. CONCLUSIONS: Hippocampal calcification was a frequent finding on CT in this cohort of stroke patients and was independently positively associated with hyperlipidaemia and diabetes mellitus, suggesting an atherosclerotic origin. KEY POINTS: • Hippocampal calcification is prevalent in over 30% of cerebrovascular disease patients. • Prevalence increases from 8% below 40 to 45% over 80 years. • Hippocampal calcification is associated with cardiovascular risk factors hyperlipidaemia and diabetes mellitus.

Hippocampal Calcification on Computed Tomography in Relation to Cognitive Decline in Memory Clinic Patients: A Case-Control Study.

BACKGROUND: It was recently shown that calcification of the hippocampus can be detected on computed tomography (CT) images and these calcifications occur in up to 20% of people over 50 years of age. However, little is known about hippocampal calcification and its relation to cognition and cognitive decline. Therefore, the aim of this study was to (1) determine the prevalence of hippocampal calcification on CT in memory clinic patients controls, and (2) to assess its relation with cognitive decline. METHODS: 67 patients from a memory clinic (cases) were matched by age and gender to a control group. In both groups, hippocampal calcification was assessed by two raters on thin slice, non-contrast enhanced brain CT images. Calcifications were scored bilaterally on presence and severity (absent, mild, moderate, severe). Mini Mental State Exam (MMSE) score was determined in cases. RESULTS: Hippocampal calcification presence was significantly higher in cases (N = 26, 38.8%) compared to controls (N = 9, 13.4%) (P < .01) with an odds ratio of 4.40 (95%CI: 1.63-14.87). In cases, MMSE score was significantly lower in those with hippocampal calcification compared to those without (21.6 vs 24.5, p = .02). CONCLUSION: In this case-control study we found significantly more hippocampal calcification in patients with cognitive decline as compared to controls. Furthermore, within the cases, MMSE score was significantly lower in those with hippocampal calcification.

Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations.

BACKGROUND: White matter hyperintensities (WMH), lacunes and microbleeds are regarded as typical MRI expressions of cerebral small vessel disease (SVD) and they are highly prevalent in the elderly. However, clinical expression of MRI defined SVD is generally moderate and heterogeneous. By reviewing studies that directly correlated postmortem MRI and histopathology, this paper aimed to characterise the pathological substrates of SVD in order to create more understanding as to its heterogeneous clinical manifestation. SUMMARY: Postmortem studies showed that WMH are also heterogeneous in terms of histopathology. Damage to the tissue ranges from slight disentanglement of the matrix to varying degrees of myelin and axonal loss. Glial cell responses include astrocytic reactions--for example, astrogliosis and clasmatodendrosis--as well as loss of oligodendrocytes and distinct microglial responses. Lipohyalinosis, arteriosclerosis, vessel wall leakage and collagen deposition in venular walls are recognised microvascular changes. Suggested pathogenetic mechanisms are ischaemia/hypoxia, hypoperfusion due to altered cerebrovascular autoregulation, blood-brain barrier leakage, inflammation, degeneration and amyloid angiopathy. Only a few postmortem MRI studies have addressed lacunes and microbleeds to date. Cortical microinfarcts and changes in the normal appearing white matter are 'invisible' on conventional MRI but are nevertheless expected to contribute substantially to clinical symptoms. CONCLUSION: Pathological substrates of WMH are heterogeneous in nature and severity, which may partly explain the weak clinicoradiological associations found in SVD. Lacunes and microbleeds have been relatively understudied and need to be further investigated. Future studies should also take into account 'MRI invisible' SVD features and consider the use of, for example, quantitative MRI techniques, to increase the sensitivity of MRI for these abnormalities and study their effects on clinical functioning.