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.A utobiographical memory is one of the multifaceted forms of human memory that constitutes a major source for selfidentity, self-continuity, and self-awareness of an individual's life. Episodic autobiographical recollection includes conscious awareness for specific episodic situations embedded in time and space, and the ability of mental reliving of episodes of a person's history along the subjective and mental time axis (1). Considering the phenomenological experience of remembering, episodic recollection involving re-experiencing requires autonoetic consciousness in contrast to semantic knowledge of memory, which is associated with noetic consciousness (2).It is generally accepted that the hippocampus plays a critical role in episodic memory, including autobiographical memory, as neuroimaging data show hippocampal activation in autobiographical memory retrieval tasks, supporting that the hippocampus is an integral structure of the autobiographical network (3, 4). The involvement of the hippocampus culminates in the question of the temporal contribution of the hippocampal-neocortical interaction in the consolidation and recollection of remote episodic memory (5). One view, according to the standard model of consolidation, considers the hippocampus as a temporary relay structure that facilitates the transition of newly encoded hippocampus-dependant memory traces to its permanent storage and consolidation in neocortical structures, resulting in hippocampus-independent remote memories (6). This transitory role of the hippocampus is thought to be reflected in the temporal gradient of retrograde amnesia seen in patients with lesions to the medial temporal lobe (MTL). Evidence for this time-limited role of the hippocampus has come from lesion studies of amnestic patients and neuroimaging studies (7,8). In contrast, the multiple trace theory (MTT) postulates a permanent contribution of the hippocampus in retrieving and recollection in terms of a binding module for episodic memories (9). This v...

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.

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.

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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