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.

Download full-text


Available from: Bryce A Mander
    • "Several limitations should be considered when interpreting our findings.Hayes, 2013;Kerti et al., 2013;Mander et al., 2013 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Midlife obesity has been associated with increased dementia risk, yet reports on brain structure and function are mixed. We therefore assessed the effects of body mass index (BMI) on gray matter volume (GMV) and cognition in a well-characterized sample of community-dwelled older adults. GMV was measured using 3T-neuroimaging in 617 participants (258 women, 60-80 years, BMI 17-41 kg/m2). Also, cognitive performance and various confounders including hypertension, diabetes and APOE-genotype were assessed. A higher BMI correlated significantly with lower GMV in multiple brain regions, including (pre)frontal, temporal, insular and occipital cortex, thalamus, putamen, amygdala and cerebellum, even after adjusting for confounders. Also, lower GMV in prefrontal and thalamic areas partially mediated negative effects of (1) higher BMI and (2) higher age on memory performance. We here showed that a higher BMI in older adults is associated with widespread gray matter alterations, irrespective of obesity-related co-morbidities and other confounders. Our results further indicate that a higher BMI induces structural alterations that translate into subtle impairments in memory performance in aging.
    No preview · Article · Jan 2016
  • Source
    • "Ainsi, lorsque le matériel utilisé est pertinent sur le plan personnel ou met en jeu une composante émotionnelle, les différences liées à l'âge seraient moins franches. Récemment, Mander et al. (2013) ont comparé les performances mnésiques, les données EEG et des données d'imagerie de sujets jeunes et âgés. Les auteurs ont observé que les performances mnésiques des sujets âgés lors d'une épreuve de mémoire épisodique (apprentissage de paires constituées d'un mot et d'un non mot) étaient inférieures à celles des sujets jeunes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Le sommeil est un moment privilégié favorisant la consolidation des souvenirs en mémoire à long terme. Les travaux menés au cours des dernières années ont permis de préciser les substrats neurobiologiques sous-tendant cet effet bénéfique du sommeil sur la mémoire et ont abouti à la proposition de deux modèles : l’hypothèse du dialogue hippocampo-néocortical et la théorie de l’homéostasie synaptique (ou recalibrage synaptique). Le vieillissement et, de manière plus marquée la maladie d’Alzheimer, s’accompagnent de troubles du sommeil qui semblent participer aux troubles de la consolidation mnésique. Dans cet article, nous proposons une synthèse des études portant sur les liens entre sommeil et mémoire, et sur la façon dont ces liens sont modifiés pendant le vieillissement normal et pathologique.
    Full-text · Article · Dec 2015 · Biologie Aujourd'hui
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Dec 2015 · SpringerPlus
Show more

We use cookies to give you the best possible experience on ResearchGate. Read our cookies policy to learn more.