IC-P-094: Medial temporal lobe changes preceding symptom onset of mild cognitive impairment: The BIOCARD Cohort

Abstract Epilepsy incidence and prevalence peaks in older adults yet systematic studies of brain ageing and cognition in older adults with epilepsy remain limited. Here, we characterize patterns of cortical atrophy and cognitive impairment in 73 older adults with temporal lobe epilepsy (>55 years) and compare these patterns to those observed in 70 healthy controls and 79 patients with amnestic mild cognitive impairment, the prodromal stage of Alzheimer’s disease. Patients with temporal lobe epilepsy were recruited from four tertiary epilepsy surgical centres; amnestic mild cognitive impairment and control subjects were obtained from the Alzheimer’s Disease Neuroimaging Initiative database. Whole brain and region of interest analyses were conducted between patient groups and controls, as well as between temporal lobe epilepsy patients with early-onset (age of onset <50 years) and late-onset (>50 years) seizures. Older adults with temporal lobe epilepsy demonstrated a similar pattern and magnitude of medial temporal lobe atrophy to amnestic mild cognitive impairment. Region of interest analyses revealed pronounced medial temporal lobe thinning in both patient groups in bilateral entorhinal, temporal pole, and fusiform regions (all P < 0.05). Patients with temporal lobe epilepsy demonstrated thinner left entorhinal cortex compared to amnestic mild cognitive impairment (P = 0.02). Patients with late-onset temporal lobe epilepsy had a more consistent pattern of cortical thinning than patients with early-onset epilepsy, demonstrating decreased cortical thickness extending into the bilateral fusiform (both P < 0.01). Both temporal lobe epilepsy and amnestic mild cognitive impairment groups showed significant memory and language impairment relative to healthy control subjects. However, despite similar performances in language and memory encoding, patients with amnestic mild cognitive impairment demonstrated poorer delayed memory performances relative to both early and late-onset temporal lobe epilepsy. Medial temporal lobe atrophy and cognitive impairment overlap between older adults with temporal lobe epilepsy and amnestic mild cognitive impairment highlights the risks of growing old with epilepsy. Concerns regarding accelerated ageing and Alzheimer’s disease co-morbidity in older adults with temporal lobe epilepsy suggests an urgent need for translational research aimed at identifying common mechanisms and/or targeting symptoms shared across a broad neurological disease spectrum.

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Evidence that volume of anterior medial temporal lobe is reduced in seniors destined for mild cognitive impairment

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2008.08.010 ◽

2010 ◽

Vol 31 (7) ◽

pp. 1099-1106 ◽

Cited By ~ 41

Author(s):

Sarah B. Martin ◽

Charles D. Smith ◽

Heather R. Collins ◽

Fred A. Schmitt ◽

Brian T. Gold

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Temporal Lobe ◽

Medial Temporal Lobe

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CSF biomarkers and medial temporal lobe atrophy predict dementia in mild cognitive impairment

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2006.05.006 ◽

2007 ◽

Vol 28 (7) ◽

pp. 1070-1074 ◽

Cited By ~ 100

Author(s):

F.H. Bouwman ◽

S.N.M. Schoonenboom ◽

W.M. van der Flier ◽

E.J. van Elk ◽

A. Kok ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Csf Biomarkers ◽

Medial Temporal Lobe Atrophy ◽

Lobe Atrophy

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Measurements of medial temporal lobe atrophy for prediction of Alzheimer's disease in subjects with mild cognitive impairment

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2013.02.002 ◽

2013 ◽

Vol 34 (8) ◽

pp. 2003-2013 ◽

Cited By ~ 49

Author(s):

Lies Clerx ◽

Ineke A. van Rossum ◽

Leah Burns ◽

Dirk L. Knol ◽

Philip Scheltens ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Medial Temporal Lobe Atrophy ◽

Lobe Atrophy

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T2 heterogeneity as an in vivo marker of microstructural integrity in medial temporal lobe subfields in ageing and mild cognitive impairment

10.1101/2020.11.03.20225177 ◽

2020 ◽

Author(s):

Alfie R. Wearn ◽

Volkan Nurdal ◽

Esther Saunders-Jennings ◽

Michael J. Knight ◽

Christopher R. Madan ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Learning Task ◽

Quantitative Mri ◽

Associate Learning ◽

Age Related ◽

Brain Changes

ABSTRACTA better understanding of early brain changes that precede loss of independence in diseases like Alzheimer’s disease (AD) is critical for development of disease-modifying therapies. Quantitative MRI, such as T2 relaxometry, can identify microstructural changes relevant to early stages of pathology. Recent evidence suggests heterogeneity of T2 may be a more informative measure of early pathology than absolute T2. Here we test whether T2 markers of brain integrity precede the volume changes we know are present in established AD and whether such changes are most marked in medial temporal lobe (MTL) subfields known to be most affected early in AD. We show that T2 heterogeneity was greater in people with mild cognitive impairment (MCI; n=49) compared to healthy older controls (n=99) in all MTL subfields, but this increase was greatest in MTL cortices, and smallest in dentate gyrus. This reflects the spatio-temporal progression of neurodegeneration in AD. T2 heterogeneity in the entorhinal cortex also predicted cognitive decline over a year in people with MCI, where measures of volume or T2 in any other subfield or whole hippocampus could not. Increases in T2 heterogeneity in MTL cortices may reflect localised pathological change and may present as one of the earliest detectible brain changes prior to atrophy. Finally, we describe a mechanism by which memory, as measured by accuracy and reaction time on a paired associate learning task, deteriorates with age. Age-related memory deficits were explained in part by lower subfield volumes, which in turn were directly associated with greater T2 heterogeneity. We propose that tissue with high T2 heterogeneity represents extant tissue at risk of permanent damage but with the potential for therapeutic rescue. This has implications for early detection of neurodegenerative disease.

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Corneal Nerve and Brain Imaging in Mild Cognitive Impairment and Dementia

Journal of Alzheimer s Disease ◽

10.3233/jad-200678 ◽

2020 ◽

Vol 77 (4) ◽

pp. 1533-1543

Author(s):

Eiman Al-Janahi ◽

Georgios Ponirakis ◽

Hanadi Al Hamad ◽

Surjith Vattoth ◽

Ahmed Elsotouhy ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Diagnostic Accuracy ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Medial Temporal Lobe Atrophy ◽

Non Invasive ◽

Corneal Confocal Microscopy ◽

Corneal Nerve ◽

Lobe Atrophy

Background: Visual rating of medial temporal lobe atrophy (MTA) is an accepted structural neuroimaging marker of Alzheimer’s disease. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic technique that detects neuronal loss in peripheral and central neurodegenerative disorders. Objective: To determine the diagnostic accuracy of CCM for mild cognitive impairment (MCI) and dementia compared to medial temporal lobe atrophy (MTA) rating on MRI. Methods: Subjects aged 60–85 with no cognitive impairment (NCI), MCI, and dementia based on the ICD-10 criteria were recruited. Subjects underwent cognitive screening, CCM, and MTA rating on MRI. Results: 182 subjects with NCI (n = 36), MCI (n = 80), and dementia (n = 66), including AD (n = 19, 28.8%), VaD (n = 13, 19.7%), and mixed AD (n = 34, 51.5%) were studied. CCM showed a progressive reduction in corneal nerve fiber density (CNFD, fibers/mm2) (32.0±7.5 versus 24.5±9.6 and 20.8±9.3, p < 0.0001), branch density (CNBD, branches/mm2) (90.9±46.5 versus 59.3±35.7 and 53.9±38.7, p < 0.0001), and fiber length (CNFL, mm/mm2) (22.9±6.1 versus 17.2±6.5 and 15.8±7.4, p < 0.0001) in subjects with MCI and dementia compared to NCI. The area under the ROC curve (95% CI) for the diagnostic accuracy of CNFD, CNBD, CNFL compared to MTA-right and MTA-left for MCI was 78% (67–90%), 82% (72–92%), 86% (77–95%) versus 53% (36–69%) and 40% (25–55%), respectively, and for dementia it was 85% (76–94%), 84% (75–93%), 85% (76–94%) versus 86% (76–96%) and 82% (72–92%), respectively. Conclusion: The diagnostic accuracy of CCM, a non-invasive ophthalmic biomarker of neurodegeneration, was high and comparable with MTA rating for dementia but was superior to MTA rating for MCI.

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