Association of imaging abnormalities of the subcallosal septal area with Alzheimer's disease and mild cognitive impairment

Abstract

AimTo evaluate the use the distance between the adjacent septal nuclei as a surrogate marker of septal area atrophy seen in Alzheimer's disease (AD).Materials & MethodsInterseptal distance (ISD) was measured, blind to clinical details, in 250 patients who underwent computed tomography (CT) of the brain at University Hospital of Wales. Clinical details including memory problem history were retrieved. An ISD cut-off value that discriminated those with and without memory symptoms was sought. ISD measurements were also made in 20 AD patients. To test both the method and the defined cut-off, measurements were then made in an independent cohort of 21 mild cognitive impairment (MCI) patients and 45 age-matched healthy controls, in a randomised and blinded fashion.ResultsISD measurement was achieved in all patients. In 28 patients with memory symptoms, the mean ISD was 5.9 mm compared with 2.3 mm in those without overt symptoms (p=0.001). The optimum ISD cut-off value was 4 mm (sensitivity 85.7% and specificity 85.8%). All AD patients had an ISD of >4 mm (mean ISD= 6.1 mm). The mean ISD for MCI patients was 3.84 mm compared with 2.18 mm in age-matched healthy controls (p=0.001). Using a 4 mm cut-off correctly categorised 10 mild cognitive impairment patients (47.6%) and 38 healthy controls (84.4%).ConclusionISD is a simple and reliable surrogate measurement for septal area atrophy, applicable to CT and magnetic resonance imaging (MRI). It can be used to help select patients for further investigation.

Leveraging genetic diversity in mice to inform individual differences in brain microstructure and memory

“…Weight loss commonly occurs in prodromal and clinical stages of AD ( White et al, 1996 ; Sergi et al, 2013 ), and mouse models of AD exhibit hypothalamic gene expression levels that correlate to both weight loss and cognitive deficits ( Dai et al, 2022 ). The septum and pallidum have been reported to undergo AD-related morphological changes ( Teipel et al, 2005 ; Gan et al, 2017 ), elicit hippocampal theta oscillations ( Hangya et al, 2009 ; Chee et al, 2015 ), and modulate hippocampal epileptogenesis ( Miller et al, 1994 ), which is observed in human AD patients ( Lam et al, 2017 ) and AD mouse models ( Palop and Mucke, 2009 ). Lastly, the habenula is implicated in motivation and behavioral regulation ( Hikosaka et al, 2008 ).…”

Visualization of atrophy of medial temporal lobes and the septal nuclei in patients with transient ischaemic attack and controls

“…Inter-septal distance (ISD) is defined as the minimum distance between the septal nuclei of each hemisphere. In accordance with the methodology outlined by Gan and colleagues, [11] the distance between the medial convexities of the septal nuclei of each hemisphere, posterior to the anterior cerebral arteries, was used for this marker. This measurement was performed on T1 images by an expert neurologist (PAB).…”

“…Larger MTA scores have been associated with global cognitive impairment one year after ischaemic stroke [10] . Additionally, the interseptal distance (ISD), or distance between adjacent septal nuclei, has recently been proposed as a practical measure of septal atrophy seen in AD, and has shown high sensitivity and specificity for distinguishing patients with and without memory impairment as well as MCI patients from controls [11] and so may be a valid marker of neurodegeneration. The clinical utility of these low-cost measures have not been thoroughly explored in the cont of predicting cognitive impairment in a TIA population.…”

Practical microscopic neuroanatomy of the limbic system and basal forebrain identifiable on clinical 3T MRI

“…Milder ISD increase can be seen in mild cognitive impairment (MCI). 1 Paradoxical septal area hypertrophy (antiepileptic septal-hippocampal system) may be seen in MTS due to seizure related increased retrograde transport of nerve growth factor from hippocampus to septal area. 2

Figure 1.Sagittal graphic (a) and consecutive parasagittal to midline sagittal 3D FLAIR images (b–d) demonstrating the 3-arches configuration of limbic system.

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“…Milder ISD increase can be seen in mild cognitive impairment (MCI). 1 Paradoxical septal area hypertrophy (antiepileptic septalhippocampal system) may be seen in MTS due to seizure related increased retrograde transport of nerve growth factor from hippocampus to septal area. 2 Hippocampus (Figure 2) consists of two distinctive layers of GM, namely, cornu ammonis (CA) and gyrus dentatus (GD).…”