scholarly journals Medial temporal lobe connectivity and its associations with cognition in early Alzheimer’s disease

Brain ◽  
2020 ◽  
Vol 143 (4) ◽  
pp. 1233-1248 ◽  
Author(s):  
David Berron ◽  
Danielle van Westen ◽  
Rik Ossenkoppele ◽  
Olof Strandberg ◽  
Oskar Hansson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Functional Connectivity ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Amyloid Β ◽  
Temporal System ◽  
Early Alzheimer’S Disease

Abstract Human episodic memory critically depends on subregions of the medial temporal lobe, which are part of functional brain systems such as the anterior-temporal and the posterior-medial system. Here we analysed how Alzheimer’s pathology affects functional connectivity within these systems. Data from 256 amyloid-β-negative cognitively unimpaired, 103 amyloid-β-positive cognitively unimpaired, and 83 amyloid-β-positive individuals with mild cognitive impairment were analysed. Amyloid-β and tau pathology were measured using the CSF amyloid-β42/40 ratio and phosphorylated tau, respectively. We found that amyloid-β-positive cognitively unimpaired individuals were mainly characterized by decreased functional connectivity between the medial temporal lobe and regions in the anterior-temporal system, most prominently between left perirhinal/entorhinal cortices and medial prefrontal cortex. Furthermore, correlation analysis in this group revealed decreasing functional connectivity between bilateral perirhinal/entorhinal cortices, anterior hippocampus and posterior-medial regions with increasing levels of phosphorylated tau. The amyloid-β-positive individuals with mild cognitive impairment mostly exhibited reduced connectivity between the medial temporal lobe and posterior-medial regions, predominantly between the anterior hippocampus and posterior cingulate cortex. In addition, they showed hyperconnectivity within the medial temporal lobe and its immediate proximity. Lower medial temporal-cortical functional connectivity networks resulting from the group comparisons of cognitively unimpaired individuals were associated with reduced memory performance and more rapid longitudinal memory decline as shown by linear mixed-effects regression analysis. Finally, we found that reduced medial temporal-cortical connectivity in mildly cognitively impaired individuals was related to reduced entorhinal thickness and white matter integrity of the parahippocampal cingulum and the fornix. No such relationships were found in cognitively unimpaired individuals. In conclusion, our findings show that the earliest changes in preclinical Alzheimer’s disease might involve decreased connectivity within the anterior-temporal system, and early changes in connectivity might be related to memory impairment, but not to structural changes. With disease progression and increased tau pathology, medial temporal functional connectivity with posterior-medial regions seems to be increasingly impaired. In individuals with mild cognitive impairment, reduced functional connectivity is associated with structural brain changes as well as the emergence of locally increased connectivity patterns. Thus, functional connectivity between the medial temporal lobe and the anterior-temporal and posterior-medial system could serve as stage-specific functional markers in early Alzheimer’s disease.

scholarly journals Differential medial temporal lobe and default-mode network functional connectivity and morphometric changes in Alzheimer’s Disease

2017 ◽  
Author(s):  
Kamil A. Grajski ◽  
Steven L. Bressler ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Functional Connectivity ◽  
Temporal Lobe ◽  
Default Mode Network ◽  
Medial Temporal Lobe ◽  
Resting State Functional Connectivity ◽  
Default Mode

AbstractWe report group level differential detection of medial temporal lobe resting-state functional connectivity disruption and morphometric changes in the transition from cognitively normal to early mild cognitive impairment in an age-, education- and gender-matched 105 subjects Alzheimer’s Disease Neuroimaging Initiative dataset. In mild Alzheimer’s Disease, but not early mild cognitive impairment, characteristic brain atrophy was detected in FreeSurfer estimates of cortical thickness and subcortical and hippocampal subfield volumes. By contrast, functional connectivity analysis detected earlier significant changes. In early mild cognitive impairment these changes involved medial temporal lobe regions of transentorhinal, perirhinal and entorhinal cortices (associated with the earliest stages of neurofibrillary changes in Alzheimer’s Disease), hippocampus, parahippocampal gyrus and temporal pole, and cortical regions comprising or co-activated with the default-mode network, including rostral and medial prefrontal cortex, anterior cingulate cortex, precuneus and inferior temporal cortex. Key findings include: a) focal and bilaterally symmetric spatial organization of affected medial temporal lobe regions; b) mutual hyperconnectivity bilaterally involving ventral medial temporal lobe structures (temporal pole, uncus); and c) dorsal medial temporal lobe hypoconnectivity with anterior and posterior midline default-mode network nodes. These findings position medial temporal lobe resting state functional connectivity as a candidate biomarker of an Alzheimer’s Disease pathophysiological cascade, potentially in advance of clinical biomarkers, and coincident with biomarkers of the earliest stages of Alzheimer’s neuropathology. Our results indicate that medial temporal lobe resting-state functional connectivity should be further investigated as a potential biomarker in the diagnosis of Alzheimer’s Disease.HighlightsFunctional connectivity change seen before structural change in Alzheimer’s DiseaseMedial temporal lobes mutually hyper-connect in mild cognitive impairmentMedial temporal lobe and default mode network decouple in mild cognitive impairmentLoci of functional change in hippocampi are focal with bilaterally symmetric featuresNonmonotonic functional connectivity changes in Alzheimer’s Disease progression

scholarly journals Atrophy and cognitive profiles in older adults with temporal lobe epilepsy are similar to mild cognitive impairment

Brain ◽  
2020 ◽  
Author(s):  
Erik Kaestner ◽  
Anny Reyes ◽  
Austin Chen ◽  
Jun Rao ◽  
Anna Christina Macari ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Late Onset ◽  
Amnestic Mild Cognitive Impairment

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.

scholarly journals Longitudinal plasma p-tau217 is increased in early stages of Alzheimer’s disease

Brain ◽  
2020 ◽  
Vol 143 (11) ◽  
pp. 3234-3241 ◽  
Author(s):  
Niklas Mattsson-Carlgren ◽  
Shorena Janelidze ◽  
Sebastian Palmqvist ◽  
Nicholas Cullen ◽  
Anna L Svenningsson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amyloid Β ◽  
Linear Mixed Effects ◽  
Three Samples ◽  
Longitudinal Plasma ◽  
Early Alzheimer’S Disease ◽  
Alzheimer’S Disease Dementia

Abstract Plasma levels of tau phosphorylated at threonine-217 (p-tau217) is a candidate tool to monitor Alzheimer’s disease. We studied 150 cognitively unimpaired participants and 100 patients with mild cognitive impairment in the Swedish BioFINDER study. P-tau217 was measured repeatedly for up to 6 years (median three samples per person, median time from first to last sample, 4.3 years). Preclinical (amyloid-β-positive cognitively unimpaired, n = 62) and prodromal (amyloid-β-positive mild cognitive impairment, n = 49) Alzheimer’s disease had accelerated p-tau217 compared to amyloid-β-negative cognitively unimpaired (β  =  0.56, P < 0.001, using linear mixed effects models) and amyloid-β-negative mild cognitive impairment patients (β  =  0.67, P < 0.001), respectively. Mild cognitive impairment patients who later converted to Alzheimer’s disease dementia (n = 40) had accelerated p-tau217 compared to other mild cognitive impairment patients (β  =  0.79, P < 0.001). P-tau217 did not change in amyloid-β-negative participants, or in patients with mild cognitive impairment who did not convert to Alzheimer’s disease dementia. For 80% power, 109 participants per arm were required to observe a slope reduction in amyloid-β-positive cognitively unimpaired (71 participants per arm in amyloid-β-positive mild cognitive impairment). Longitudinal increases in p-tau217 correlated with longitudinal worsening of cognition and brain atrophy. In summary, plasma p-tau217 increases during early Alzheimer’s disease and can be used to monitor disease progression.

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

2013 ◽  
Vol 34 (8) ◽  
pp. 2003-2013 ◽  
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

P2-176: The medial temporal lobe index (MTLi) is a simple and reliable method for predicting conversion from mild cognitive impairment to Alzheimer's disease

2013 ◽  
Vol 9 ◽  
pp. P414-P415
Author(s):  
Manuel Menendez ◽  
Marta Martínez Rivera ◽  
Tania Álvarez-Avellon ◽  
López-Muñiz Alfonso ◽  
Jose Antonio Vega
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Reliable Method

scholarly journals Visual Evaluation of Medial Temporal Lobe Atrophy as a Clinical Marker of Conversion from Mild Cognitive Impairment to Dementia and for Predicting Progression in Patients with Mild Cognitive Impairment and Mild Alzheimer's Disease

2017 ◽  
Vol 44 (1-2) ◽  
pp. 12-24 ◽  
Author(s):  
Karin Persson ◽  
Maria Lage Barca ◽  
Rannveig Sakshaug Eldholm ◽  
Lena Cavallin ◽  
Jūratė Šaltytė Benth ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Delayed Recall ◽  
Medial Temporal Lobe Atrophy ◽  
Adjusted Model ◽  
Lobe Atrophy

Background/Aims: To evaluate whether visual assessment of medial temporal lobe atrophy (vaMTA) can predict 2-year conversion from mild cognitive impairment (MCI) to dementia and progression of MCI and Alzheimer's disease dementia as measured by the Clinical Dementia Rating Scale Sum of Boxes score (CDR-SB). Methods: vaMTA was performed in 94 patients with MCI according to the Winblad criteria and in 124 patients with AD according to ICD-10 and NINCDS-ADRDA criteria. Demographic data, the Consortium to Establish a Registry for Alzheimer's Disease 10-word delayed recall, APOE ɛ4 status, Cornell Scale for Depression in Dementia, and comorbid hypertension were used as covariates. Results: vaMTA was associated with MCI conversion in an unadjusted model but not in an adjusted model (p = 0.075), where delayed recall and APOE ɛ4 status were significant predictors. With CDR-SB change as the outcome, an interaction between vaMTA and diagnosis was found, but in the adjusted model only delayed recall and age were significant predictors. For vaMTA below 2, the association between vaMTA and CDR-SB change differed between diagnostic groups. Similar results were found based on a trajectory analysis. Conclusion: In adjusted models, memory function, APOE ɛ4 status and age were significant predictors of disease progression, not vaMTA. The association between vaMTA and CDR-SB change was different in patients with MCI and Alzheimer's disease dementia.

Volumes of Medial Temporal Lobe Structures in Patients with Alzheimer’s Disease and Mild Cognitive Impairment (and in Healthy Controls)

1998 ◽  
Vol 43 (1) ◽  
pp. 60-68 ◽  
Author(s):  
Jack S. Krasuski ◽  
Gene E. Alexander ◽  
Barry Horwitz ◽  
Eileen M. Daly ◽  
Declan G.M. Murphy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Healthy Controls
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