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Spatial navigation critically underlies hippocampal-entorhinal circuit function that is early affected in Alzheimer's disease (AD). There is growing evidence that AD pathophysiology dynamically interacts with the sleep/wake cycle impairing hippocampal memory. To elucidate sleep-dependent consolidation in a cohort of symptomatic AD patients (n = 12, 71.25 ± 2.16 years), we tested hippocampal place learning by means of a virtual reality task and verbal memory by a word-pair association task before and after a night of sleep. Our results show an impaired overnight memory retention in AD compared with controls in the verbal task, together with a significant reduction of sleep spindle activity (i.e., lower amplitude of fast sleep spindles, p = 0.016) and increased duration of the slow oscillation (SO; p = 0.019). Higher spindle density, faster down-to-upstate transitions within SOs, and the time delay between SOs and nested spindles predicted better memory performance in healthy controls but not in AD patients. Our results show that mnemonic processing and memory consolidation in AD is slightly impaired as reflected by dysfunctional oscillatory dynamics and spindle-SO coupling during NonREM sleep. In this translational study based on experimental paradigms in animals and extending previous work in healthy aging and preclinical disease stages, our results in symptomatic AD further deepen the understanding of the memory decline within a bidirectional relationship of sleep and AD pathology.
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Doença de Alzheimer , Consolidação da Memória , Humanos , Consolidação da Memória/fisiologia , Polissonografia , Sono/fisiologia , Memória/fisiologia , Transtornos da Memória/etiologiaRESUMO
PURPOSE: Quality of Life (QoL) is associated with a bandwidth of lifestyle factors that can be subdivided into fixed and potentially modifiable ones. We know too little about the role of potentially modifiable factors in comparison to fixed ones. This study examines four aspects of QoL and its associations with 15 factors in a sample of elderly primary care patients with a high risk of dementia. The main objectives are (a) to determine the role of the factors in this particular group and (b) to assess the proportion of fixed and potentially modifiable factors. METHOD: A high-risk group of 1030 primary care patients aged between 60 and 77 years (52.1% females) were enrolled in "AgeWell.de," a cluster-randomized, controlled trial. This paper refers to the baseline data. The multi-component intervention targets to decrease the risk of dementia by optimization of associated lifestyle factors. 8 fixed and 7 modifiable factors potentially influencing QoL served as predictors in multiple linear regressions. RESULTS: The highest proportion of explained variance was found in psychological health and age-specific QoL. In comparison to health-related QoL and physical health, the modifiable predictors played a major role (corr. R2: 0.35/0.33 vs. 0.18), suggesting that they hold a greater potential for improving QoL. CONCLUSION: Social engagement, body weight, instrumental activities of daily living, and self-efficacy beliefs appeared as lifestyle factors eligible to be addressed in an intervention program for improving QoL. TRIAL REGISTRATION: German Clinical Trials Register, reference number: DRKS00013555. Date of registration: 07.12.2017.
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Demência , Atenção Primária à Saúde , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Feminino , Idoso , Masculino , Pessoa de Meia-Idade , Demência/psicologia , Estilo de Vida , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: We investigated the effectiveness of a multidomain intervention to preserve cognitive function in older adults at risk for dementia in Germany in a cluster-randomized trial. METHODS: Individuals with a Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk score ≥ 9 aged 60 to 77 years were recruited. After randomization of their general practitioner (GP), patients received a multidomain intervention (including optimization of nutrition and medication, and physical, social, and cognitive activity) or general health advice and GP treatment as usual over 24 months. Primary outcome was global cognitive performance (composite z score, based on domain-specific neuropsychological tests). RESULTS: Of 1030 participants at baseline, n = 819 completed the 24-month follow-up assessment. No differences regarding global cognitive performance (average marginal effect = 0.010, 95% confidence interval: -0.113, 0.133) were found between groups at follow-up. Perceived restrictions in intervention conduct by the COVID-19 pandemic did not impact intervention effectiveness. DISCUSSION: The intervention did not improve global cognitive performance. HIGHLIGHTS: Overall, no intervention effects on global cognitive performance were detected. The multidomain intervention improved health-related quality of life in the total sample. In women, the multidomain intervention reduced depressive symptoms. The intervention was completed during the COVID-19 pandemic.
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COVID-19 , Disfunção Cognitiva , Demência , Idoso , Feminino , Humanos , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/prevenção & controle , Demência/epidemiologia , Demência/prevenção & controle , Pandemias , Qualidade de Vida , Fatores de RiscoRESUMO
OBJECTIVES: Growing evidence suggests a protective effect of high mental demands at work on cognitive function in later life. However, evidence on corresponding associations in older adults at increased risk for dementia is currently lacking. This study investigates the association between mental demands at work and cognitive functioning in the population of the AgeWell.de-trial. METHODS: Cross-sectional investigation of the association between global cognitive functioning (Montreal Cognitive Assessment) and mental demands at work in older individuals at increased risk for dementia (Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE)score ≥ 9; n = 941, age: 60-77 years). Occupational information was matched to Occupational Information Network (O*NET)-descriptors. Associations between cognitive function and O*NET-indices executive, verbal and novelty were investigated using generalized linear models. RESULTS: Higher values of index verbal (b = .69, p = .002) were associated with better cognitive function when adjusting for covariates. No association was observed for indices executive (b = .37, p = .062) and novelty (b = .45, p = .119). Higher education, younger age, and employment were linked to better cognitive function, while preexisting medical conditions did not change the associations. Higher levels of depressive symptomatology were associated with worse cognitive function. CONCLUSIONS: Higher levels of verbal demands at work were associated with better cognitive function for older adults with increased dementia risk. This suggests an advantage for older persons in jobs with high mental demands even after retirement and despite prevalent risk factors. Longitudinal studies are warranted to confirm these results and evaluate the potential of workplaces to prevent cognitive decline through increased mental demands.
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Disfunção Cognitiva , Demência , Idoso , Idoso de 80 Anos ou mais , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Demência/diagnóstico , Demência/epidemiologia , Humanos , Local de TrabalhoRESUMO
Autobiographical memories in our lives are critically dependent on temporal lobe structures. However, the contribution of CA1 neurons in the human hippocampus to the retrieval of episodic autobiographical memory remains elusive. In patients with a rare acute transient global amnesia, highly focal lesions confined to the CA1 field of the hippocampus can be detected on MRI. We studied the effect of these lesions on autobiographical memory using a detailed autobiographical interview including the remember/know procedure. In 14 of 16 patients, focal lesions in the CA1 sector of the hippocampal cornu ammonis were detected. Autobiographical memory was significantly affected over all time periods, including memory for remote periods. Impairment of episodic memory and autonoetic consciousness exhibited a strong temporal gradient extending 30 to 40 y into the past. These results highlight the distinct and critical role of human hippocampal CA1 neurons in autobiographical memory retrieval and for re-experiencing detailed episodic memories.
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Amnésia Global Transitória/fisiopatologia , Região CA1 Hipocampal/fisiologia , Memória Episódica , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Amnésia Global Transitória/patologia , Região CA1 Hipocampal/patologia , Região CA1 Hipocampal/fisiopatologia , Estudos de Casos e Controles , Estado de Consciência/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Fatores de TempoRESUMO
Background: Studies demonstrate associations between low social activity in older adults and cognitive decline. Little has been investigated regarding which factors are associated with low social activity in older adults at increased risk of dementia. Objective: We investigate which sociodemographic, psychological, health-related, and environmental factors are associated with low social activity in older adults at increased risk of dementia. Additionally, we describe the stages of health behavior change, the types of social activities, and the duration of the current level of social activity. Methods: We used baseline data of 1,015 participants from the AgeWell.de trial. We conducted logistic and Poisson regression analyses to investigate factors associated with low social activity. We report descriptive statistics on the stages of change in the sample, the types of social activities most frequently pursued, and the duration of the current level of social activity. Results: Lower income, non-usage of public transport, depressive symptoms, cognitive, mobility, and hearing impairment were negatively associated with social activity. The majority of the sample was in the maintenance stage, followed by the precontemplation stage. The most common social activities were traveling and hobbies with others. Participants have maintained their current level of social activity for several years. Conclusions: We identified a lack of resources (income, transport), depressive symptoms and poorer health (cognitive, mobility and hearing impairment) as barriers to social activity. Interventions promoting social activity in older adults at risk of dementia may specifically target individuals with these risk factors. Low-threshold opportunities for social activity may be particularly beneficial.
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Disfunção Cognitiva , Demência , Perda Auditiva , Humanos , Idoso , Estudos Transversais , Disfunção Cognitiva/psicologia , Comportamento Social , Demência/epidemiologia , Demência/psicologia , Perda Auditiva/psicologiaRESUMO
BACKGROUND: Aim of this study was to detect predictors of better adherence to the AgeWell.de-intervention, a two-year randomized multi-domain lifestyle intervention against cognitive decline. METHODS: Data of 317 intervention group-participants comprising a risk group for dementia (Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) score of ≥ 9; mean age 68.9 years, 49.5% women) from the AgeWell.de intervention study were analysed. Regression models with four blocks of predictors (sociodemographic, cognitive and psychosocial, lifestyle factors and chronic conditions) were run on adherence to the components of nutrition, enhancement of social and physical activity and cognitive training. Adherence to each component was operationalised by assessing the degree of goal achievement per component at up to seven time points during the intervention period, measured using a 5-point Likert scale (mean score of goal achievement). RESULTS: Increasing age was negatively associated with adherence, while higher education positively predicted adherence. Participants with better mental state (Montreal Cognitive Assessment (MoCA)-score > 25) at baseline and higher self-efficacy adhered better. Diabetes and cardiovascular conditions were not associated with adherence, whereas smoking negatively affected adherence. Highest education and quitting smoking in the past were the only predictors associated with all four intervention components. CONCLUSION: Results identified predictors for better and worse adherence. Particularly self-efficacy seems to be of considerable influence on adherence. This should be considered when designing future intervention trials. TRIAL REGISTRATION: German Clinical Trials Register (ref. number: DRKS00013555).
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Disfunção Cognitiva , Estilo de Vida , Autoeficácia , Humanos , Feminino , Masculino , Idoso , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/psicologia , Cooperação do Paciente/psicologia , Pessoa de Meia-Idade , Exercício Físico/psicologia , Demência/psicologia , Demência/prevenção & controle , Demência/epidemiologia , Idoso de 80 Anos ou maisRESUMO
While regular physical-activity (PA) is beneficial, multimorbid individuals at increased dementia risk may exhibit reduced PA levels. Thus, a more comprehensive understanding of mediating factors responsible for inactivity in this population is needed. This study investigated the impact of a multimodal intervention on PA changes at 24-month follow-up and associated mediating factors among community-dwelling patients aged 60-77, with increased dementia risk determined by the CAIDE Dementia Risk Score. Of 1030 participants recruited, 819 completed the assessment. Thus, a generalized estimating equations model initially assessed differences in PA over 24 months, followed by a tree analysis identifying mediating factors influencing PA changes post-intervention. While no significant effect on regular PA was found during the follow-up (P = .674), subgroup analysis revealed improved self-efficacy (P = .000) associated with increased engagement in PA. Incorporating self-efficacy elements into future strategies is crucial for promoting PA among individuals with multimorbidity and at increased dementia risk.
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Demência , Exercício Físico , Autoeficácia , Humanos , Masculino , Feminino , Idoso , Exercício Físico/fisiologia , Pessoa de Meia-Idade , Vida Independente , Seguimentos , Multimorbidade , Fatores de RiscoRESUMO
BACKGROUND: General practitioners (GPs) play a crucial role in identifying cognitive impairment and dementia and providing post-diagnostic care. This study investigates (1) how promising GP consider lifestyle changes to maintain cognitive performance in general, (2) GP beliefs about the power of modifiable health and lifestyle factors to maintain cognitive performance, and (3) whether those beliefs vary by GP age. METHODS: As part of the AgeWell.de trial, GPs (n = 72) completed a process evaluation questionnaire assessing their perspectives on lifestyle changes to preserve cognitive performance in elderly patients. In greater detail, their perceived efficacy of established risk and protective factors was investigated using a 5-point Likert scale. Descriptive statistical analyses were performed for research question (1) and (2). Spearman´s rank correlations and ordinal logistic regressions were used to answer research question (3). All results were interpreted exploratively. RESULTS: GPs rated the overall chance of lifestyle changes maintaining cognitive performance quite neutral with a median score of 3.0 (IQR = 2.0). They rated the efficacy of all the modifiable health and lifestyle factors high, with increase in physical and social activity ((Mdn = 5.0, IQR = 1.0) receiving the highest ratings with the narrowest range. Spearman's rank correlation indicated a significant positive relationship between age and the belief in "Optimization of nutrition" for preventing cognitive decline and dementia (ρ = .255, p = .041). However, ordinal logistic regressions showed no significant relationships between age and GP ratings of lifestyle change efficacy. CONCLUSION: These findings highlight the positive perception of GPs on the efficacy of modifiable health and lifestyle factors for preventing cognitive decline and dementia. TRIAL REGISTRATION: The AgeWell.de trial is registered in the German Clinical Trials Register (DRKS; trial identifier: DRKS00013555, Registration Date 07 December 2017).
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Demência , Clínicos Gerais , Estilo de Vida , Humanos , Demência/prevenção & controle , Demência/psicologia , Masculino , Feminino , Clínicos Gerais/psicologia , Pessoa de Meia-Idade , Atitude do Pessoal de Saúde , Inquéritos e Questionários , Adulto , Idoso , Cognição , Exercício Físico/psicologiaRESUMO
Our study aims to examine the associations of sociodemographic factors, social support, resilience, and perceptions of the COVID-19 pandemic with late-life depression and anxiety symptoms in a cardiovascular risk group and a matched sample from the German general population during the beginning of the pandemic and draw a comparison regarding psychosocial characteristics. Data of n = 1236 participants (aged 64-81 years) were analyzed, with n = 618 participants showing a cardiovascular risk profile, and n = 618 participants from the general population. The cardiovascular risk sample had slightly higher levels of depressive symptoms and felt more threatened by the virus due to pre-existing conditions. In the cardiovascular risk group, social support was associated with less depressive and anxiety symptoms. In the general population, high social support was associated with less depressive symptoms. Experiencing high levels of worries due to COVID-19 was associated with more anxiety in the general population. Resilience was associated with less depressive and anxiety symptoms in both groups. Compared to the general population, the cardiovascular risk group showed slightly higher levels of depressive symptomatology even at the beginning of the pandemic and may be supported by addressing perceived social support and resilience in prevention programs targeting mental health.
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COVID-19 , Doenças Cardiovasculares , Humanos , Pandemias , Depressão , Fatores de Risco , Ansiedade , Fatores de Risco de Doenças CardíacasRESUMO
Background: With the outbreak of COVID-19, government measures including social distancing and restrictions of social contacts were imposed to slow the spread of the virus. Since older adults are at increased risk of severe disease, they were particularly affected by these restrictions. These may negatively affect mental health by loneliness and social isolation, which constitute risk factors for depressiveness. We aimed to analyse the impact of perceived restriction due to government measures on depressive symptoms and investigated stress as mediator in an at-risk-population in Germany. Methods: Data were collected in April 2020 from the population of the AgeWell.de-study, including individuals with a Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score ≥9, using the depression subscale of the Brief Symptom Inventory (BSI-18) and the Perceived Stress Scale (PSS-4). Feeling restricted due to COVID-19 government measures was surveyed with a standardized questionnaire. Stepwise multivariate regressions using zero-inflated negative binomial models were applied to analyse depressive symptoms, followed by a general structural equation model to assess stress as mediator. Analysis were controlled for sociodemographic factors as well as social support. Results: We analysed data from 810 older adults (mean age = 69.9, SD = 5). Feeling restricted due to COVID-19 government measures was linked to increased depressiveness (b = 0.19; p < 0.001). The association was no longer significant when adding stress and covariates (b = 0.04; p = 0.43), while stress was linked to increased depressive symptoms (b = 0.22; p < 0.001). A final model confirms the assumption that the feeling of restriction is mediated by stress (total effect: b = 0.26; p < 0.001). Conclusion: We found evidence that feeling restricted due to COVID-19 government measures is associated with higher levels of depressive symptoms in older adults at increased risk for dementia. The association is mediated by perceived stress. Furthermore, social support was significantly associated with less depressive symptoms. Thus, it is of high relevance to consider possible adverse effects of government measures related to COVID-19 on mental health of older people.
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COVID-19 , Demência , Humanos , Idoso , COVID-19/epidemiologia , COVID-19/psicologia , Estudos Transversais , Saúde Mental , SARS-CoV-2 , Governo , Atenção Primária à SaúdeRESUMO
To develop effective dementia prevention strategies, it is necessary to understand risk factors, associated factors and early signs of dementia. Subjective cognitive decline (SCD) is the earliest form of dementia. The aim of this study is to assess depression as a factor that is significantly associated with SCD. The data of 1030 general practitioner patients from the AgeWell.de-study (60-77 years; CAIDE dementia risk score ≥ 9) were analysed. A descriptive analysis was conducted using validated instruments like the Geriatric depression scale (GDS), Lubben social network scale (LSNS-6) and education classes according to CASMIN (Comparative Analysis of Social Mobility in Industrial Nations). A multivariate regression model with the dependent variable SCD was calculated. Of the 1030 participants, 5.9% had depressive symptoms and 31.3% SCD. The group with depressive symptoms showed significantly higher body-mass-index (p = 0.005), lower education class (p = 0.022), lower LSNS-6 score (p < 0.001), higher sports activity (p < 0.001), and more sleeping problems (p = 0.026). In the regression model a higher GDS-score [Odds ratio (OR): 1.219 (p < 0.001)], more sleeping problems [OR: 1.550 (p = 0.017)] and higher education class [middle/high: OR: 1.474/1.875 (p = 0.037/0.004)] were significantly associated with SCD. This study identified depressive symptoms, sleeping problems, and higher education classes as factors associated with SCD, which can represent an early form of dementia.
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This study aims to describe social network and social participation and to assess associations with depressive symptoms in older persons with increased risk for dementia in Germany. We conducted a cross-sectional observational study in primary care patients (aged 60−77) as part of a multicenter cluster-randomized controlled trial (AgeWell.de). We present descriptive and multivariate analyses for social networks (Lubben Social Network Scale and subscales) and social participation (item list of social activities) and analyze associations of these variables with depressive symptoms (Geriatric Depression Scale). Of 1030 included patients, 17.2% were at risk for social isolation (Lubben Social Network Scale < 12). Looking at the subscales, a reduced non-family network was found almost twice as often as a reduced family network. Patients with depressive symptoms had significantly smaller social networks than patients without depression (p < 0.001). They rather engaged in social activities of low involvement level or no weekly social activity at all (p < 0.001). The study shows associations of depressive symptoms with a decreased social network and less social participation in elderly participants. Sufficient non-family contacts and weekly social activities seem to play an important role in mental health and should be encouraged in elderly primary care patients.
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PURPOSE: To investigate the association between health-related quality of life and ego integrity among the oldest old. MATERIALS AND METHODS: Cross-sectional data were taken from follow-up wave 9 of the multicenter prospective cohort study "Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+)" (AgeQualiDe). Our analytical sample comprised n = 495 observations. Mean age was 90.2 years (SD: 2.7 years). Health-related quality of life was quantified using the EQ-5D-3L questionnaire (including the visual analogue scale EQ-VAS). Ego integrity was measured using the Ego Integrity Scale. RESULTS: Regressions showed an association between decreased ego integrity and problems with 'usual activities', 'pain/discomfort' and 'anxiety/depression'. Furthermore, regressions showed a marginally significant association between decreased ego integrity and problems with 'mobility' and a decreased EQ-VAS score. Ego integrity was not significantly associated with problems with 'self-care'. CONCLUSIONS: Findings stress the importance of health-related quality of life for ego integrity among the oldest old. Future studies are required to clarify the underlying mechanisms.
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Ego , Qualidade de Vida , Idoso de 80 Anos ou mais , Estudos Transversais , Humanos , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
Targeting dementia prevention, first trials addressing multiple modifiable risk factors showed promising results in at-risk populations. In Germany, AgeWell.de is the first large-scale initiative investigating the effectiveness of a multi-component lifestyle intervention against cognitive decline. We aimed to investigate the recruitment process and baseline characteristics of the AgeWell.de participants to gain an understanding of the at-risk population and who engages in the intervention. General practitioners across five study sites recruited participants (aged 60-77 years, Cardiovascular Risk Factors, Aging, and Incidence of Dementia/CAIDE dementia risk score ≥ 9). Structured face-to-face interviews were conducted with eligible participants, including neuropsychological assessments. We analyzed group differences between (1) eligible vs. non-eligible participants, (2) participants vs. non-participants, and (3) between intervention groups. Of 1176 eligible participants, 146 (12.5%) dropped out before baseline; the study population was thus 1030 individuals. Non-participants did not differ from participants in key sociodemographic factors and dementia risk. Study participants were M = 69.0 (SD = 4.9) years old, and 52.1% were women. The average Montreal Cognitive Assessment/MoCA score was 24.5 (SD = 3.1), indicating a rather mildly cognitively impaired study population; however, 39.4% scored ≥ 26, thus being cognitively unimpaired. The bandwidth of cognitive states bears the interesting potential for differential trial outcome analyses. However, trial conduction is impacted by the COVID-19 pandemic, requiring adjustments to the study protocol with yet unclear methodological consequences.
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Disfunção Cognitiva/prevenção & controle , Estilo de Vida , Seleção de Pacientes , Idoso , Feminino , Alemanha , Envelhecimento Saudável , Humanos , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
Learning and the formation of memory are reflected in various memory systems in the human brain such as the hippocampus based declarative memory system and the striatum-cortex based system involved in motor sequence learning. It is a matter of debate how both memory systems interact in humans during learning and consolidation and how this interaction is influenced by sleep. We studied the effect of an acute dysfunction of hippocampal CA1 neurons on the acquisition (on-line condition) and off-line changes of a motor skill in patients with a transient global amnesia (TGA). Sixteen patients (68 ± 4.4 yrs) were studied in the acute phase and during follow-up using a declarative and procedural test, and were compared to controls. Acute TGA patients displayed profound deficits in all declarative memory functions. During the acute amnestic phase, patients were able to acquire the motor skill task reflected by increasing finger tapping speed across the on-line condition, albeit to a lesser degree than during follow-up or compared to controls. Retrieval two days later indicated a greater off-line gain in motor speed in patients than controls. Moreover, this gain in motor skill performance was negatively correlated to the declarative learning deficit. Our results suggest a differential interaction between procedural and declarative memory systems during acquisition and consolidation of motor sequences in older humans. During acquisition, hippocampal dysfunction attenuates fast learning and thus unmasks the slow and rigid learning curve of striatum-based procedural learning. The stronger gains in the post-consolidation condition in motor skill in CA1 lesioned patients indicate a facilitated consolidation process probably occurring during sleep, and suggest a competitive interaction between the memory systems. These findings might be a reflection of network reorganization and plasticity in older humans and in the presence of CA1 hippocampal pathology.
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Amnésia Global Transitória/fisiopatologia , Aprendizagem/fisiologia , Destreza Motora/fisiologia , Idoso , Amnésia Global Transitória/psicologia , Feminino , Humanos , Masculino , Memória/fisiologia , Rememoração Mental/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Desempenho Psicomotor/fisiologia , Sono/fisiologiaRESUMO
The CA1 (cornu ammonis) region of hippocampus is selectively vulnerable to a variety of metabolic and cytotoxic insults, which is mirrored in a delayed neuronal death of CA1 neurons. The basis and mechanisms of this regional susceptibility of CA1 neurons are poorly understood, and the correlates in human diseases affecting the hippocampus are not clear. Adopting a translational approach, the lesion evolution, temporal course, pattern of diffusion changes, and damage in hippocampal CA1 in acute neurologic disorders were studied using high-resolution magnetic resonance imaging. In patients with hippocampal ischemia (n=50), limbic encephalitis (n=30), after status epilepticus (n=17), and transient global amnesia (n=53), the CA1 region was selectively affected compared with other CA regions of the hippocampus. CA1 neurons exhibited a maximum decrease of apparent diffusion coefficient (ADC) 48 to 72 hours after the insult, irrespective of the nature of the insult. Hypoxic-ischemic insults led to a significant lower ADC suggesting that the ischemic insult results in a stronger impairment of cellular metabolism. The evolution of diffusion changes show that CA1 diffusion lesions mirror the delayed time course of the pathophysiologic cascade typically observed in animal models. Studying the imaging correlates of hippocampal damage in humans provides valuable insight into the pathophysiology and neurobiology of the hippocampus.
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Região CA1 Hipocampal/patologia , Neurônios/patologia , Adulto , Idoso , Amnésia Global Transitória/patologia , Isquemia Encefálica/patologia , Região CA1 Hipocampal/fisiopatologia , Transtornos Cerebrovasculares/classificação , Transtornos Cerebrovasculares/patologia , Estudos de Coortes , Imagem de Difusão por Ressonância Magnética , Encefalite/patologia , Feminino , Hipocampo/patologia , Humanos , Hipóxia Encefálica/patologia , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estado Epiléptico/patologiaRESUMO
The transient global amnesia (TGA) is a rare amnesic syndrome that is characterized by an acute onset episode of an anterograde and retrograde amnesia. Its origin is still debated, but there is evidence for psychological factors involved in TGA. In neuroimaging, selective lesions in the CA1 field of the hippocampus can be detected, a region that is particularly involved in the processing of memory, stress and emotion. The aim of this study was to assess the role of psychological stress in TGA by studying the prevalence of stress related precipitating events and individual stress-related personality profiles as well as coping strategies in patients. The hypothesis of a functional differentiation of the hippocampus in mnemonic and stress-related compartments was also evaluated. From all 113 patients, 18% (n = 24) patients experienced emotional and psychological stress episodes directly before the TGA. In a cohort of 21 acute patients, TGA patients tend to cope with stress less efficiently and less constructively than controls. Patients who experienced a stress related precipitant event exhibited a higher level of anxiety in comparison to non-stress patients and controls. However, there was no difference between the general experience of stress and the number of stress inducing life events. The majority of patients (73%) did show typical magnetic resonance imaging (MRI) lesions in the CA1 region of the hippocampal cornu ammonis. There was no clear association between stressful events, distribution of hippocampal CA1 lesions and behavioral patterns during the TGA. Disadvantageous coping strategies and an elevated anxiety level may increase the susceptibility to psychological stress which may facilitate the pathophysiological cascade in TGA. The findings suggest a role of emotional stress factors in the manifestation of TGA in a subgroup of patients. Stress may be one trigger involved in the emergence of transient lesions in the hippocampal CA1 region, which are thought to be the structural and functional correlate of TGA.