Demencia prevenció: A korai diagnózistól a személyre szabott intervencióig

Összefoglaló. Az elmúlt évtizedekben a várható élettartam emelkedésével drámai mértékben nőtt a demencia előfordulásának gyakorisága, melynek hátterében leggyakrabban az Alzheimer-kór áll. A rendkívül ígéretes, biomarkereken, agyi képalkotáson és mesterséges intelligencián alapuló megközelítéseknek köszönhetően egyre szélesebb körű információink vannak a betegség kialakulásáról és lefolyásáról, új kapukat nyitva ezzel a demencia korai diagnózisa és a személyre szabott terápia felé. Míg az új kutatási irányzatok előnye vitathatatlan, a nagy mennyiségű kutatási adat kezelése, illetve a betegség korai szakaszban történő azonosítása több biztonsági kérdést felvet. A korai diagnózis mellett egyre nagyobb hangsúly helyeződik az intervencióra, a demenciára hajlamosító tényezőkbe történő beavatkozás által. Summary. As a consequence of increasing life expectancy, the number of those living with dementia is rising. While Alzheimer’s disease (AD) constitutes the most common cause of dementia, the origin of AD is unknown. Furthermore, in the absence of effective treatment, therapy focuses on the cognitive and behavioural symptoms of the disease, and the wellbeing of the patient. AD is characterised by a pronounced impairment experienced in one or more cognitive domains, and the criterion of the diagnosis is the presence of aggregated proteins in the brain leading to neuron death, and eventually to the loss of cognitive abilities. As a result of the latest technological advances, several biological markers (biomarkers) of AD pathology were identified. The biomarkers can be obtained using positron emission tomography or measured from cerebrospinal fluid, and lately from blood serum and plasma as well. Magnetic resonance imaging provides an important measure of brain atrophy, a biomarker of neurodegeneration and neuronal injury. The structure of the brain shows significant alterations as a function of neuronal loss, with cortical thinning and tissue density changes, mainly starting from the medial temporal lobes (also including the hippocampus playing a prominent role in memory functions), and extending to the temporoparietal regions, with observed changes in the activity of the different functional brain networks as well. A major challenge in defeating AD is that in most cases, the disease is recognised subsequent to the appearance of the decline in cognitive abilities, hampering everyday life. Previous studies identified a preclinical stage of AD, where the biomarkers indicative of the disease are present in the absence of detectable cognitive symptoms. This early, preclinical stage – with the use of artificial intelligence-based techniques – has been suggested to be a promising window for the early detection of the disease, and also for the prediction of individual disease trajectories, allowing for the thorough planning of patient management. While the benefit of the early diagnosis is unequivocal, it raises a number of important ethical and safety issues. Besides the tremendous effort of developing effective medical treatments, the importance of intervention stands in the centre of scientific interest. The proposed prevention and intervention methods target the potentially modifiable risk factors of dementia, encouraging engagement in stimulating everyday activities and healthy lifestyle, to preserve longevity.

Who Are You? The Study of Personality in Patients With Anterograde Amnesia

Little is known about the role of declarative memory in the ongoing perception of one’s personality. Seven individuals who developed a rare and severe type of anterograde amnesia following damage to their medial temporal lobes were identified from our neurological patient registry. We examined the stability of their personality ratings on the Big Five Inventory over five retest periods and assessed the accuracy of their ratings via analyses of self–caregiver agreement. The patients portrayed a stable sense of self over the course of 1 year. However, their self-ratings differed from those provided by the caregivers. Intriguingly, these discrepancies diminished when caregivers retrospectively rated the patients’ personalities prior to their brain injury, suggesting that patients’ perceptions of themselves were stuck in the past. We interpret our findings to indicate that the ability to form new declarative memories is not required for maintaining a stable sense of self but may be important for updating one’s sense of self over time.

Similar patterns of 18F-FDG brain PET hypometabolism in paediatric and adult patients with long COVID: a paediatric case series

Purpose. Several weeks after COVID-19 infection, some children report the persistence or recurrence of functional complaints. This clinical presentation has been referred as “long COVID” in the adult population, and an 18F-FDG brain PET hypometabolic pattern has recently been suggested as a biomarker. Herein, we present a retrospective analysis of 7 paediatric patients with suspected long COVID who were explored by 18F-FDG brain PET exam. Metabolic brain findings were confronted to those obtained in adult patients with long COVID, in comparison to their respective age-matched control groups. Methods. Review of clinical examination, and whole-brain voxel-based analysis of 18F-FDG PET metabolism of the 7 children in comparison to 20 paediatric controls, 35 adult patients with long COVID and 44 healthy adult subjects. Results. Paediatric patients demonstrated a similair brain hypometabolic pattern as that found in adult long COVID patients, involving bilateral medial temporal lobes, brainstem and cerebellum (p-voxel < 0.001, p-cluster < 0.05 FWE-corrected), and also the right olfactory gyrus after small volume correction (p-voxel = 0.010 FWE-corrected), with partial recovery in two children at follow-up. Conclusion. These results provide arguments in favour of possible long COVID in children, with a similar functional brain involvement to those found in adults.

Structural Changes in Thalamic Nuclei Across Prodromal and Clinical Alzheimer’s Disease

Background: Increasing evidence suggests that thalamic nuclei may atrophy in Alzheimer’s disease (AD). We hypothesized that there will be significant atrophy of limbic thalamic nuclei associated with declining memory and cognition across the AD continuum. Objective: The objective of this work was to characterize volume differences in thalamic nuclei in subjects with early and late mild cognitive impairment (MCI) as well as AD when compared to healthy control (HC) subjects using a novel MRI-based thalamic segmentation technique (THOMAS). Methods: MPRAGE data from the ADNI database were used in this study (n = 540). Healthy control (n = 125), early MCI (n = 212), late MCI (n = 114), and AD subjects (n = 89) were selected, and their MRI data were parcellated to determine the volumes of 11 thalamic nuclei for each subject. Volumes across the different clinical subgroups were compared using ANCOVA. Results: There were significant differences in thalamic nuclei volumes between HC, late MCI, and AD subjects. The anteroventral, mediodorsal, pulvinar, medial geniculate, and centromedian nuclei were significantly smaller in subjects with late MCI and AD when compared to HC subjects. Furthermore, the mediodorsal, pulvinar, and medial geniculate nuclei were significantly smaller in early MCI when compared to HC subjects. Conclusion: This work highlights nucleus specific atrophy within the thalamus in subjects with early and late MCI and AD. This is consistent with the hypothesis that memory and cognitive changes in AD are mediated by damage to a large-scale integrated neural network that extends beyond the medial temporal lobes.

Autobiographical memory unknown: Pervasive autobiographical memory loss encompassing personality trait knowledge in an individual with medial temporal lobe amnesia

Autobiographical memory consists of distinct memory types varying from highly abstract to episodic. Self trait knowledge, which is considered one of the more abstract types of autobiographical memory, is thought to rely on regions of the autobiographical memory neural network implicated in schema representation, including the medial prefrontal cortex, and critically, not the medial temporal lobes. The current case study introduces an individual who, as a consequence of bilateral posterior cerebral artery strokes, experienced extensive medial temporal lobe damage with sparing of the medial prefrontal cortex. Interestingly, in addition to severe retrograde and anterograde episodic and autobiographical fact amnesia, this individual’s self trait knowledge was impaired for his current and pre-morbid personality traits. Yet, further assessment revealed that this individual had preserved conceptual knowledge for personality traits, could reliably and accurately rate another person’s traits, and could access his own self-concept in a variety of ways. In addition to autobiographical memory loss, he demonstrated impairment on non-personal semantic memory tests, most notably on tests requiring retrieval of unique knowledge. This rare case of amnesia suggests a previously unreported role for the medial temporal lobes in personal trait knowledge, which we propose reflects the critical role of this neural region in the storage and retrieval of personal semantics that are experience-near, meaning autobiographical facts grounded in spatiotemporal contexts.

Memorable navigation: Assessing the influence of way-finding in spatial clustering

Navigating around an environment and remembering the events that took place within it are crucial cognitive abilities that have been linked to the Hippocampus and medial temporal lobes (MTL). Scene Construction Theory (SCT) has proposed that a function of the Hippocampus is the implicit and continuous construction of scenes to help prediction of upcoming environment. Scenes, as highly efficient means of packaging information, underpin in coordination with other brain regions, episodic memory (EM), spatial navigation, future thinking and perhaps even dreaming and mind-wandering. We examined the conditions in which spatial contiguity of stimuli influences the organization of memory by examining spatial clustering (SC) phenomenon. In this research, an augmented reality (AR) system was used to test 14 participants in a spatially dependent memory task which assessed the SC differences between active navigators and passive spectators. We confirmed our hypothesis that navigators use spatial information as part of the retrieval process in free recall, as they tended to sequentially recall any two neighboring otherwise unrelated items. We also found a significant correlation between SC and correct recall performance supporting our second hypothesis. These results may be valuable for design of learning applications, especially dealing with large amounts of data. Research on Alzheimer's and other neurodegenerative diseases may also benefit from our approach. Future studies may assess the role of encoding and retrieval modality and participant's use of mnemonic strategies.

Hippocampal Volume Influences The Correlations Between White Matter Disruption and Tau Protein in aMCI and mild AD

Background: Alzheimer’s disease (AD) is classically considered a grey matter (GM) disease that starts in the transentorhinal cortex and spreads to limbic and neocortical regions. However, white matter (WM) damage could be more severe and widespread than expected cortical atrophy. The role of AD biomarkers and WM integrity throughout the brain is unclear, especially in amnestic Mild Cognitive Impairment (aMCI) patients, a possible prodromal AD dementia stage. If WM damage can be detected even before the development of cortical atrophy and overt dementia and in the AD process, Aβ42 Tau (and its phosphorylated form) could directly affect WM. Methods: We analyzed in this study 183 individuals - 48 aMCI in the AD continuum (altered CSF Aβ42), 30 patients with very mild or mild AD dementia and 105 normal controls. All subjects underwent neuropsychological evaluation and MRI exams. aMCI and mild AD individuals were also submitted to CSF puncture to evaluate AD biomarkers.Results: We observed several significant differences in WM integrity regarding the DTI measures between individuals and we found significant correlations between fornix and right cingulum hippocampal tracts and Tau and p-Tau proteins. Conclusions: We hypothesize that significant correlations with tracts anatomically far from more well-established GM atrophic regions, like medial temporal lobes, would support a more direct effect of pathological proteins on WM, whereas medial temporal lobe (MTL) correlations would favor WD and/or a direct spreading of pathology from the hippocampus.

Hippocampal Volume Influences the Correlations Between White Matter Disruption and Tau Protein in aMCI and mild AD

BackgroundAlzheimer’s disease (AD) is classically considered a grey matter (GM) disease that starts in transentorhinal cortex and spread to limbic and neocortical regions. However, withe matter (WM) damage could be more severe and widespread than expected cortical atrophy. It is not clear the role of AD biomarkers and WM integrity throughout the brain, especially including amnestic Mild Cognitive Impairment (aMCI) patients, a possible prodromal AD dementia stage, if WM damage can be detected even before the development of cortical atrophy and overt dementia and in AD process, Aβ42 Tau (and its phosphorylated form) could directly affect WM.MethodsWe analyzed in this study 183 individuals - 48 aMCI in the AD continuum (altered CSF Aβ42), 30 patients with very mild or mild AD dementia and 105 normal controls. All subjects underwent neuropsychological evaluation and MRI exam. aMCI and mild AD individuals were also submitted to CSF puncture to evaluate AD biomarkers.ResultsWe observed several significant differences in WM integrity regarding the DTI measures between individuals and we found significant correlations between fornix and right cingulum hippocampal tracts and Tau and p-Tau proteins.ConclusionsWe hypothesize that significant correlations with tracts anatomically far from more well-established GM atrophic regions, like medial temporal lobes, would support a more direct effect of pathological proteins on WM, whereas medial temporal lobe (MTL) correlations would favor WD and/or a direct spreading of pathology from hippocampus.