APOE ɛ4 Allele Moderates the Association Between Basal Forebrain Nuclei Volumes and Allocentric Navigation in Older Adults Without Dementia

2022 ◽  
pp. 1-17
Author(s):  
Ondrej Lerch ◽  
Martina Pařízková ◽  
Martin Vyhnálek ◽  
Zuzana Nedelská ◽  
Jakub Hort ◽  
...  
Keyword(s):  
Older Adults ◽  
Basal Forebrain ◽  
Medial Temporal Lobe ◽  
Structural Equation ◽  
Brain Aging ◽  
Late Onset ◽  
Brain Regions ◽  
Real Space ◽  
Complex Model ◽  
E4 Allele

Background: Cholinergic deficit and medial temporal lobe (MTL) atrophy are hallmarks of Alzheimer’s disease (AD) leading to early allocentric spatial navigation (aSN) impairment. APOE ɛ4 allele (E4) is a major genetic risk factor for late-onset AD and contributes to cholinergic dysfunction. Basal forebrain (BF) nuclei, the major source of acetylcholine, project into multiple brain regions and, along with MTL and prefrontal cortex (PFC), are involved in aSN processing. Objective: We aimed to determine different contributions of individual BF nuclei atrophy to aSN in E4 positive and E4 negative older adults without dementia and assess whether they operate on aSN through MTL and PFC or independently from these structures. Methods: 120 participants (60 E4 positive, 60 E4 negative) from the Czech Brain Aging Study underwent structural MRI and aSN testing in real-space arena setting. Hippocampal and BF nuclei volumes and entorhinal cortex and PFC thickness were obtained. Associations between brain regions involved in aSN were assessed using MANOVA and complex model of mutual relationships was built using structural equation modelling (SEM). Results: Path analysis based on SEM modeling revealed that BF Ch1-2, Ch4p, and Ch4ai nuclei volumes were indirectly associated with aSN performance through MTL (pch1 - 2 = 0.039; pch4p = 0.042) and PFC (pch4ai = 0.044). In the E4 negative group, aSN was indirectly associated with Ch1-2 nuclei volumes (p = 0.015), while in the E4 positive group, there was indirect effect of Ch4p nucleus (p = 0.035). Conclusion: Our findings suggest that in older adults without dementia, BF nuclei affect aSN processing indirectly, through MTL and PFC, and that APOE E4 moderates these associations.

scholarly journals The Combined Effect of APOE and BDNF Val66Met Polymorphisms on Spatial Navigation in Older Adults

2020 ◽  
Vol 78 (4) ◽  
pp. 1473-1492
Author(s):  
Jan Laczó ◽  
Katerina Cechova ◽  
Martina Parizkova ◽  
Ondrej Lerch ◽  
Ross Andel ◽  
...  
Keyword(s):  
Older Adults ◽  
Verbal Memory ◽  
Medial Temporal Lobe ◽  
Brain Aging ◽  
Spatial Navigation ◽  
Memory Performance ◽  
Brain Mri ◽  
Brain Regions ◽  
Real Space ◽  
Egocentric Navigation

Background: The apolipoprotein E (APOE) ɛ4 allele is associated with episodic memory and spatial navigation deficits. The brain-derived neurotrophic factor (BDNF) Met allele may further worsen memory impairment in APOE ɛ4 carriers but its role in APOE ɛ4-related spatial navigation deficits has not been established. Objective: We examined influence of APOE and BDNF Val66Met polymorphism combination on spatial navigation and volumes of selected navigation-related brain regions in cognitively unimpaired (CU) older adults and those with amnestic mild cognitive impairment (aMCI). Methods: 187 participants (aMCI [n = 116] and CU [n = 71]) from the Czech Brain Aging Study were stratified based on APOE and BDNF Val66Met polymorphisms into four groups: ɛ4–/BDNFVal/Val, ɛ4–/BDNFMet, ɛ4+/BDNFVal/Val, and ɛ4+/BDNFMet. The participants underwent comprehensive neuropsychological examination, brain MRI, and spatial navigation testing of egocentric, allocentric, and allocentric delayed navigation in a real-space human analogue of the Morris water maze. Results: Among the aMCI participants, the ɛ4+/BDNFMet group had the least accurate egocentric navigation performance (p < 0.05) and lower verbal memory performance than the ɛ4–/BDNFVal/Val group (p = 0.007). The ɛ4+/BDNFMet group had smaller hippocampal and entorhinal cortical volumes than the ɛ4–/BDNFVal/Val (p≤0.019) and ɛ4–/BDNFMet (p≤0.020) groups. Among the CU participants, the ɛ4+/BDNFMet group had less accurate allocentric and allocentric delayed navigation performance than the ɛ4–/BDNFVal/Val group (p < 0.05). Conclusion: The combination of APOE ɛ4 and BDNF Met polymorphisms is associated with more pronounced egocentric navigation impairment and atrophy of the medial temporal lobe regions in individuals with aMCI and less accurate allocentric navigation in CU older adults.

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 (&gt;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 &lt;50 years) and late-onset (&gt;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 &lt; 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 &lt; 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 Multiple pathways of reserve simultaneously present in cognitively normal older adults

Neurology ◽  
2017 ◽  
Vol 90 (3) ◽  
pp. e197-e205 ◽  
Author(s):  
Hwamee Oh ◽  
Qolamreza R. Razlighi ◽  
Yaakov Stern
Keyword(s):  
Older Adults ◽  
Task Switching ◽  
Reading Ability ◽  
Brain Aging ◽  
Brain Activation ◽  
Brain Regions ◽  
Amyloid Deposition ◽  
Neural Pathways ◽  
Intellectual Activity ◽  
Cognitively Normal

ObjectiveTo examine neural correlates of intellectual activity underlying multiple pathways imparting reserve by testing that higher intellectual activity is associated with lower brain amyloid pathology, greater gray matter (GM) volume, and differential task-evoked brain activation levels as a function of amyloid positivity status among clinically intact older adults.MethodsEighty-two cognitively normal older adults and 46 healthy young participants underwent fMRI during task switching. All older participants completed 18F-florbetaben-PET and an individual's amyloid positivity status was determined. To assess GM volume, T1-weighted high-resolution structural images were processed using voxel-based morphometry. As lifestyle factors, intellectual activity was estimated by a composite score of vocabulary, reading ability, and years of education.ResultsAcross all older participants, intellectual activity was associated with lower amyloid deposition in lateral and medial frontoparietal and temporal lobes but higher amyloid deposition in superior frontal and parietal cortices, larger GM volume across widespread brain regions, and reduced brain activation during task switching. These patterns of associations, however, differed by amyloid positivity status. While the patterns of associations remained similar among amyloid-negative older adults, among amyloid-positive older adults, intellectual activity was associated with increased amyloid deposition in frontoparietal cortices and increased activation during task.ConclusionsIntellectual activity simultaneously exerts both neuroprotective and compensatory effects via multiple neural pathways that promote optimal brain aging and help maintain normal cognition during amyloid accumulation.

Network interactions among limbic cortices, basal forebrain, and cerebellum differentiate a tone conditioned as a Pavlovian excitor or inhibitor: fluorodeoxyglucose mapping and covariance structural modeling

1994 ◽  
Vol 72 (4) ◽  
pp. 1717-1733 ◽  
Author(s):  
A. R. McIntosh ◽  
F. Gonzalez-Lima
Keyword(s):  
Structural Equation Modeling ◽  
Discriminant Analysis ◽  
Network Analysis ◽  
Basal Forebrain ◽  
Structural Equation ◽  
Brain Regions ◽  
Retrosplenial Cortex ◽  
Equation Modeling ◽  
Regional Activity ◽  
Path Coefficients

1. The objective was to examine how opposite learned behavioral responses to the same physical tone were differentiated by the pattern of interactions between extraauditory neural regions. This was pursued using a new approach combining behavior, neuroimaging, and network analysis to integrate information about differences in regional activity with differences in the covariance relationships between brain areas. 2. A tone was used as either a Pavlovian conditioned excitor or inhibitor. Rats were conditioned with reinforced trials of a conditioned excitor (A+) intermixed with nonreinforced trials of a tone-light compound (AX-). The tone was the excitor (A+) for the tone-excitor group and was the inhibitor (X-) for the tone-inhibitor group. After conditioning, all rats were injected with [14C(U)]2-fluoro-2-deoxyglucose (FDG) and presented with the same tone. 3. FDG autoradiography was used to measure regional activity and to generate interregional correlations of activity resulting from the presentation of the tone. A stepwise discriminant analysis was used to select brain regions that differentiated the excitor from the inhibitor effects. 4. Network analysis consisted of constructing an anatomic model of the brain regions, selected by the discriminant analysis, linking the regions with their known anatomical connections. Then, functional models for the tone-excitor and -inhibitor groups were constructed using structural equation modeling. Correlations of activity between regions were decomposed to calculate numerical weights, or path coefficients, for each anatomic path. These path coefficients were used to compare the interactions for the tone-excitor and -inhibitor models. 5. Regional differences in FDG uptake were found in the sulcal frontal cortex (SFC), lateral septum (LS), medial septum/diagonal band (MS/DB), retrosplenial cortex (RS), and dentate-interpositus nuclei of the cerebellum (DEN). Discriminant analysis selected three other regions that significantly discriminated the tone-excitor and -inhibitor groups: perirhinal cortex (PRh), nucleus accumbens (ACB), and the anteroventral nucleus of the thalamus (AVN). 6. Structural equation modeling identified two functional circuits that differentiated the groups. One involved the basal forebrain regions (LS, MS/DB, ACB) and the other limbic thalamocortical structures (SFC, RS, PRh, AVN). Differences in the interactions within these circuits were mainly in sign of the covariance relationships between regions, from positive for the tone-excitor model to negative path coefficients for the tone-inhibitor model. The path coefficient between the basal forebrain circuit and the limbic thalamocortical circuit showed the largest magnitude difference. This quantitative difference was mediated by a path from the MS/DB to PRh.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Structural Brain Correlates of Loneliness among Older Adults

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sandra Düzel ◽  
Johanna Drewelies ◽  
Denis Gerstorf ◽  
Ilja Demuth ◽  
Elisabeth Steinhagen-Thiessen ◽  
...  
Keyword(s):  
Older Adults ◽  
Individual Differences ◽  
Cognitive Processing ◽  
Emotional Regulation ◽  
Structural Equation ◽  
Brain Structures ◽  
Brain Regions ◽  
Network Size ◽  
Equation Modeling ◽  
Ample Evidence

Abstract Ample evidence indicates that loneliness in old age is associated with poor bodily and mental health. However, little is known about structural cerebral correlates of loneliness in healthy older adults. We examined such correlates in a magnetic resonance imaging (MRI) subsample of 319 older adults aged 61 to 82 years drawn from the Berlin Aging Study II. Using voxel-based morphometry (VBM) and structural equation modeling (SEM), latent hierarchical regression analyses were performed to examine associations of (i) loneliness, (ii) a range of covariates, and (iii) loneliness by covariate interactions with latent brain volume estimates of brain structures known to be involved in processing, expressing, and regulating emotions. Results from whole-brain VBM analyses showed that individuals with higher loneliness scores tended to have smaller gray matter volumes in three clusters comprising (i) the left amygdala/anterior hippocampus, (ii) the left posterior parahippocampus and (iii) the left cerebellum. Significant associations and interactions between loneliness and latent factors for the amygdala and the hippocampus were confirmed with a region-of-interest (ROI)-based approach. These findings suggest that individual differences in loneliness among older adults are correlated with individual differences in the volumes of brain regions that are central to cognitive processing and emotional regulation, also after correcting for confounders such as social network size. We discuss possible mechanisms underlying these associations and their implications.

scholarly journals Cerebral Metabolite Concentrations Are Associated With Cortical and Subcortical Volumes and Cognition in Older Adults

2021 ◽  
Vol 12 ◽  
Author(s):  
John B. Williamson ◽  
Damon G. Lamb ◽  
Eric C. Porges ◽  
Sarah Bottari ◽  
Adam J. Woods ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Aging ◽  
Structural Changes ◽  
Fluid Intelligence ◽  
Brain Aging ◽  
Neuropsychological Testing ◽  
Hippocampal Volume ◽  
Brain Regions ◽  
Cognitive Changes ◽  
Imaging And Spectroscopy

BackgroundCerebral metabolites are associated with different physiological processes in brain aging. Cortical and limbic structures play important roles in cognitive aging; however, the relationship between these structures and age remains unclear with respect to physiological underpinnings. Regional differences in metabolite levels may be related to different structural and cognitive changes in aging.MethodsMagnetic resonance imaging and spectroscopy were obtained from 117 cognitively healthy older adults. Limbic and other key structural volumes were measured. Concentrations of N-acetylaspartate (NAA) and choline-containing compounds (Cho) were measured in frontal and parietal regions. Neuropsychological testing was performed including measures of crystallized and fluid intelligence and memory.ResultsNAA in the frontal voxel was associated with limbic and cortical volumes, whereas Cho in parietal cortex was negatively associated with hippocampal and other regional volumes. Hippocampal volume was associated with forgetting, independent of age. Further, parietal Cho and hippocampal volume contributed independent variance to age corrected discrepancy between fluid and crystallized abilities.ConclusionThese findings suggest that physiological changes with age in the frontal and parietal cortices may be linked to structural changes in other connected brain regions. These changes are differentially associated with cognitive performance, suggesting potentially divergent mechanisms.

Inefficient Encoding as an Explanation for Age-Related Deficits in Recollection-Based Processing

2014 ◽  
Vol 28 (3) ◽  
pp. 148-161 ◽  
Author(s):  
David Friedman ◽  
Ray Johnson
Keyword(s):  
Older Adults ◽  
Young Adults ◽  
Cognitive Processes ◽  
Brain Activity ◽  
Memory Performance ◽  
Brain Regions ◽  
Semantic Retrieval ◽  
Age Related ◽  
The Face ◽  
Episodic Memories

A cardinal feature of aging is a decline in episodic memory (EM). Nevertheless, there is evidence that some older adults may be able to “compensate” for failures in recollection-based processing by recruiting brain regions and cognitive processes not normally recruited by the young. We review the evidence suggesting that age-related declines in EM performance and recollection-related brain activity (left-parietal EM effect; LPEM) are due to altered processing at encoding. We describe results from our laboratory on differences in encoding- and retrieval-related activity between young and older adults. We then show that, relative to the young, in older adults brain activity at encoding is reduced over a brain region believed to be crucial for successful semantic elaboration in a 400–1,400-ms interval (left inferior prefrontal cortex, LIPFC; Johnson, Nessler, & Friedman, 2013 ; Nessler, Friedman, Johnson, & Bersick, 2007 ; Nessler, Johnson, Bersick, & Friedman, 2006 ). This reduced brain activity is associated with diminished subsequent recognition-memory performance and the LPEM at retrieval. We provide evidence for this premise by demonstrating that disrupting encoding-related processes during this 400–1,400-ms interval in young adults affords causal support for the hypothesis that the reduction over LIPFC during encoding produces the hallmarks of an age-related EM deficit: normal semantic retrieval at encoding, reduced subsequent episodic recognition accuracy, free recall, and the LPEM. Finally, we show that the reduced LPEM in young adults is associated with “additional” brain activity over similar brain areas as those activated when older adults show deficient retrieval. Hence, rather than supporting the compensation hypothesis, these data are more consistent with the scaffolding hypothesis, in which the recruitment of additional cognitive processes is an adaptive response across the life span in the face of momentary increases in task demand due to poorly-encoded episodic memories.

Neuroplasticity

2019 ◽  
pp. 230-260
Author(s):  
Judy S. Reilly ◽  
Lara R. Polse
Keyword(s):  
Neural Plasticity ◽  
Late Onset ◽  
Neural Substrates ◽  
Brain Regions ◽  
Developing Brain ◽  
Perinatal Stroke ◽  
Alternative Pathways ◽  
Affective Expression ◽  
Unilateral Brain ◽  
Irreparable Damage

With respect to language, it has long been observed that children who experience early unilateral brain injury do not show the same irreparable damage as do adults with homologous late-onset strokes. Neural plasticity has been proposed as the explanation for such differential linguistic profiles; that is, the plasticity of the young, developing brain allows the possibility for extensive adaptation and organization following a neural insult. Recent research, however, suggests that there are limits to this ability to adapt and organize. Results from a another communicative system, affect, suggest that children with unilateral pre- or perinatal stroke show similar (albeit subtler) effects to adults with homologous late-onset injuries. This chapter presents findings on language development in children who sustained a pre- or perinatal unilateral stroke, and complements these studies with a discussion of affective expression in these same children. These prospective studies of children with perinatal stroke provide a unique window into the development of the neural substrates for language and affect. Specifically, they afford a context to investigate the degree to which particular brain regions may be privileged for specific behavioral functions, as well as how the developing brain adapts to organize alternative pathways in the wake of an early insult.

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