Prefrontal atrophy, disrupted NREM slow waves, and impaired hippocampal-dependent memory in aging

Sleep and Neuroimaging Laboratory, University of California, Berkeley, California, USA.
Nature Neuroscience (Impact Factor: 16.1). 01/2013; 16(3). DOI: 10.1038/nn.3324
Source: PubMed


Aging has independently been associated with regional brain atrophy, reduced slow wave activity (SWA) during non-rapid eye movement (NREM) sleep and impaired long-term retention of episodic memories. However, whether the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. We found that age-related medial prefrontal cortex (mPFC) gray-matter atrophy was associated with reduced NREM SWA in older adults, the extent to which statistically mediated the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex functional connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represents a contributing factor to age-related cognitive decline in later life.

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    • "Although it is widely documented that sleep fragmentation and EDS are strongly correlated with both aging and neurodegenerative disease, it has proven difficult to define the causal relationships among these features, and the topic remains controversial (Klerman and Dijk 2008) (Gooneratne and Vitiello 2014). One recent human study (Mander et al. 2013) elucidated a role for slow wave sleep loss in the memory retention deficits associated with healthy aging, and found that both factors were associated with atrophy of medial prefrontal cortex. The authors concluded that age-associated cortical atrophy may contribute to sleep changes which in turn impact memory, indicating that interventions aimed at improving sleep among the elderly may have marked benefits on cognitive function even in healthy patients (Miyata et al. 2013). "
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    ABSTRACT: Sleep/wake disturbance is a feature of almost all common age-related neurodegenerative diseases. Although the reason for this is unknown, it is likely that this inability to maintain sleep and wake states is in large part due to declines in the number and function of wake-active neurons, populations of cells that fire only during waking and are silent during sleep. Consistent with this, many of the brain regions that are most susceptible to neurodegeneration are those that are necessary for wake maintenance and alertness. In the present review, these wake-active populations are systematically assessed in terms of their observed pathology across aging and several neurodegenerative diseases, with implications for future research relating sleep and wake disturbances to aging and age-related neurodegeneration.
    SpringerPlus 12/2015; 4(1):25. DOI:10.1186/s40064-014-0777-6
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    • "Research has begun to link changes in sleep and cognition by suggesting that co-occurring sleep problems may uniquely contribute to cognitive deficits. Negative correlations have been observed in older adults between cognitive performance and disrupted sleep on tests of global cognitive impairment (Jelicic et al., 2002; Blackwell et al., 2006; Carvalho-Bos et al., 2007), working memory (Haimov et al., 2008; Nebes et al., 2009; Lim et al., 2012), mental speed (Oosterman et al., 2009), memory encoding (Mander et al., 2013a), memory retrieval (Westerberg et al., 2010), and memory consolidation (Wilson et al., 2012; Mander et al., 2013b; Sonni and Spencer, 2015). Beyond the contribution of disrupted sleep, disturbances in the circadian rhythm of the rest-activity cycle are notably linked to age-related changes in cognitive functioning (Lim et al., 2012). "
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    ABSTRACT: Older adults experience parallel changes in sleep, circadian rhythms, and episodic memory. These processes appear to be linked such that disruptions in sleep contribute to deficits in memory. Although more variability in circadian patterns is a common feature of aging and predicts pathology, little is known about how alterations in circadian activity rhythms within older adults influence new episodic learning. Following 10 days of recording sleep-wake patterns using actigraphy, healthy older adults underwent fMRI while performing an associative memory task. The results revealed better associative memory was related to more consistent circadian activity rhythms, independent of total sleep time, sleep efficiency, and level of physical activity. Moreover, hippocampal activity during successful memory retrieval events was positively correlated with associative memory accuracy and circadian activity rhythm (CAR) consistency. We demonstrated that the link between consistent rhythms and associative memory performance was mediated by hippocampal activity. These findings provide novel insight into how the circadian rhythm of sleep-wake cycles are associated with memory in older adults and encourage further examination of circadian activity rhythms as a biomarker of cognitive functioning. Copyright © 2015. Published by Elsevier Ltd.
    Neuropsychologia 07/2015; 75. DOI:10.1016/j.neuropsychologia.2015.07.020 · 3.30 Impact Factor
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    • "the vmPFC may medi - ate online and offline integration of new information into existing knowledge structures ( Takashima et al . , 2006 ; van Kesteren et al . , 2010 ) . Moreover , shifts from hippocampus - based to vmPFC - based rep - resentations were shown to occur , even within 24 – 48 h that included a night ' s sleep ( Gais et al . , 2007 ; Mander et al . , 2013 ) . The current findings in the EE group are consistent with these models . The functional net - work highlighted by the vmPFC seed , which included MTL structures and specifically the hippocampus , was significantly enhanced during retrieval of Remote ( post - sleep ) items , compared to recent ones . This pattern suggests that for ass"
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    ABSTRACT: Memory formation for newly acquired associations typically depends on hippocampal-neocortical interactions. Through the process of system-consolidation, the mnemonic binding role of the hippocampus is subsequently replaced by cortical hubs, such as the ventromedial prefrontal cortex (vmPFC) or the anterior temporal lobe (ATL). Here, using BOLD-fMRI, we compared retrieval of semantic associations acquired through Fast Mapping (FM) - an incidental, exclusion-based learning procedure, to retrieval of similar associations that were intentionally acquired through explicit encoding (EE). Despite an identical retrieval task, the encoding histories of the retrieved semantic associations (FM vs. EE) induced distinct neural substrates and disparate related neural dynamics in time. Retrieval of associations acquired through EE engaged the expected hippocampal and vmPFC related networks. Furthermore, retrieval intentionally encoded associations gave rise to a typical overnight increase in engagement of the vmPFC and increased vmPFC-hippocampal-neocortical functional connectivity. On the other hand, retrieval of associations acquired through FM immediately engaged an ATL related network that typically supports well-established semantic knowledge, a network that did not engage the hippocampus and the vmPFC. Moreover, FM learning was associated with minimal overnight changes in the BOLD responses and in the functional connectivity. Our findings indicate that FM may induce a direct, ATL-mediated acquisition and retention of novel arbitrary associations, bypassing the initial hippocampal-cortical representation phase. A direct, ATL-mediated acquisition following FM can support the learning and retention of new associations in young children with presumably an immature hippocampal system, and even in amnesic adults with hippocampal lesions. Copyright © 2015. Published by Elsevier Inc.
    NeuroImage 05/2015; 117. DOI:10.1016/j.neuroimage.2015.05.027 · 6.36 Impact Factor
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