Combining lifestyle risks to disentangle brain structure and functional connectivity differences in older adults

Bittner, Nóra; Jockwitz, Christiane; Mühleisen, Thomas W.; Hoffstaedter, Felix; Eickhoff, Simon B.; Moebus, Susanne; Bayen, Ute J.; Cichon, Sven; Zilles, Karl; Amunts, Katrin; Caspers, Svenja

doi:10.1038/s41467-019-08500-x

Cited by 44 publications

(50 citation statements)

References 67 publications

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“…Furthermore, Lindbergh et al [43] found a stronger segregation of the DMN, expressed by a higher within-compared to between-network RSFC, over the course of aging to be associated with higher intelligence. Bittner et al [8] integrated different aspects of lifestyle into a lifestyle risk score including smoking and alcohol intake as risk factors and social interaction and physical activity as protective factors. Higher lifestyle risk was associated with higher between-network RSFC, i.e.…”

Section: Other Factors That Might Explain the High Inter-individual Vmentioning

confidence: 99%

Resting-state networks in the course of aging—differential insights from studies across the lifespan vs. amongst the old

Jockwitz

Caspers

2021

Pflugers Arch - Eur J Physiol

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Resting-state functional connectivity (RSFC) has widely been used to examine reorganization of functional brain networks during normal aging. The extraction of generalizable age trends, however, is hampered by differences in methodological approaches, study designs and sample characteristics. Distinct age ranges of study samples thereby represent an important aspect between studies especially due to the increase in inter-individual variability over the lifespan. The current review focuses on comparing age-related differences in RSFC in the course of the whole adult lifespan versus later decades of life. We summarize and compare studies assessing age-related differences in within- and between-network RSFC of major resting-state brain networks. Differential effects of the factor age on resting-state networks can be identified when comparing studies focusing on younger versus older adults with studies investigating effects within the older adult population. These differential effects pertain to higher order and primary processing resting-state networks to a varying extent. Especially during later decades of life, other factors beyond age might come into play to understand the high inter-individual variability in RSFC.

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Section: Other Factors That Might Explain the High Inter-individual Vmentioning

confidence: 99%

Resting-state networks in the course of aging—differential insights from studies across the lifespan vs. amongst the old

Jockwitz

Caspers

2021

Pflugers Arch - Eur J Physiol

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“…Acute alcohol intake by older individuals is associated with reduced cognitive function and blunted neural responses that mediate higher order working memory and attention as compared to younger adults (Lewis et al, 2019;Squeglia et al, 2014). Moreover, magnetic resonance imaging studies have shown that moderate, nondependent, alcohol use (Mukamal et al, 2001) or moderate alcohol use combined with reduced physical activity (Bittner et al, 2019) is associated with loss of gray matter in older adults, which may contribute to alcohol-induced cognitive decline. However, other evidence suggests that moderate alcohol use does not alter age-related cognitive decline (Moussa et al, 2014) suggesting that the conditions under which low to moderate levels of alcohol use may impact health and well-being in older populations are not fully understood.…”

Section: Alcohol Age-related Cognitive Decline and Dementiamentioning

confidence: 99%

Alcohol Drinking Exacerbates Neural and Behavioral Pathology in the 3xTg-AD Mouse Model of Alzheimer’s Disease

Hoffman

Faccidomo

Kim

et al. 2019

Preprint

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder that represents the most common cause of dementia in the United States. Although the link between alcohol use and AD has been studied, preclinical research has potential to elucidate neurobiological mechanisms that underlie this interaction. This study was designed to test the hypothesis that non-dependent alcohol drinking exacerbates the onset and magnitude of AD-like neural and behavioral pathology.We first evaluated the impact of voluntary 24-h, 2-bottle choice home-cage alcohol drinking on the prefrontal cortex and amygdala neuroproteome in C57BL/6J mice and found a striking association between alcohol drinking and AD-like pathology. Bioinformatics identified the ADassociated proteins MAPT (Tau), amyloid beta precursor protein (APP), and presenilin-1 (PSEN-1) as the main modulators of alcohol-sensitive protein networks that included AD-related proteins that regulate energy metabolism (ATP5D, HK1, AK1, PGAM1, CKB), cytoskeletal development (BASP1, CAP1, DPYSL2 [CRMP2], ALDOA, TUBA1A, CFL2, ACTG1), cellular/oxidative stress (HSPA5, HSPA8, ENO1, ENO2), and DNA regulation (PURA, YWHAZ). To address the impact of alcohol drinking on AD, studies were conducted using 3xTg-AD mice that express human MAPT, APP, and PSEN-1 transgenes and develop AD-like brain and behavioral pathology. 3xTg-AD and wildtype mice consumed alcohol or saccharin for 4 months. Behavioral tests were administered during a 1-month alcohol free period. Alcohol intake induced AD-like behavioral pathologies in 3xTg-AD mice including impaired spatial memory in the Morris Water Maze, diminished sensorimotor gating as measured by prepulse inhibition, and exacerbated conditioned fear. Multiplex immunoassay conducted on brain lysates showed that alcohol drinking upregulated primary markers of AD pathology in 3xTg-AD mice: Aβ 42/40 ratio in the lateral entorhinal and prefrontal cortex and total Tau expression in the lateral entorhinal cortex and amygdala at 1-month post alcohol exposure. Immunocytochemistry showed that alcohol use upregulated expression of pTau (Ser199/Ser202) in the hippocampus, which is consistent with late stage AD. According to the NIA-AA Research Framework, these results suggest that alcohol use is associated with Alzheimer's pathology. Results also showed that alcohol use was associated with a general reduction in Akt/mTOR signaling via several phosphoproteins (IR, IRS1, IGF1R, PTEN, ERK, mTOR, p70S6K, RPS6) in multiple brain regions including hippocampus and entorhinal cortex.Dysregulation of Akt/mTOR phosphoproteins suggests alcohol may target this pathway in AD progression. These results suggest that nondependent alcohol drinking increases the onset and magnitude of AD-like neural and behavioral pathology in 3xTg-AD mice.

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“…Acute alcohol intake by older individuals is associated with reduced cognitive function and blunted neural responses that mediate higher order working memory and attention as compared to younger adults (Lewis, Garcia, Boissoneault, Price, & Nixon, 2019; Squeglia, Boissoneault, Van Skike, Nixon, & Matthews, 2014). Moreover, magnetic resonance imaging studies have shown that moderate, nondependent, alcohol use (Mukamal, Longstreth, Mittleman, Crum, & Siscovick, 2001) or moderate alcohol use combined with reduced physical activity (Bittner et al, 2019) is associated with loss of gray matter in older adults, which may contribute to alcohol-induced cognitive decline. However, other evidence suggests that moderate alcohol use does not alter age-related cognitive decline (Moussa et al, 2014) suggesting that the conditions under which low to moderate levels of alcohol use may impact health and well-being in older populations are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Alcohol drinking exacerbates neural and behavioral pathology in the 3xTg-AD mouse model of Alzheimer's disease

Hoffman

Faccidomo

Kim

et al. 2019

International Review of Neurobiology

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that represents the most common cause of dementia in the United States. Although the link between alcohol use and AD has been studied, preclinical research has potential to elucidate neurobiological mechanisms that underlie this interaction. This study was designed to test the hypothesis that nondependent alcohol drinking exacerbates the onset and magnitude of AD-like neural and behavioral pathology. We first evaluated the impact of voluntary 24-h, two-bottle choice home-cage alcohol drinking on the prefrontal cortex and amygdala neuroproteome in C57BL/6J mice and found a striking association between alcohol drinking and AD-like pathology. Bioinformatics identified the AD-associated proteins MAPT (Tau), amyloid beta precursor protein (APP), and presenilin-1 (PSEN-1) as the main modulators of alcohol-sensitive protein networks that included AD-related proteins that regulate energy metabolism (ATP5D, HK1, AK1, PGAM1, CKB), cytoskeletal development (BASP1, CAP1, DPYSL2 [CRMP2], ALDOA, TUBA1A, CFL2, ACTG1), cellular/oxidative stress (HSPA5, HSPA8, ENO1, ENO2), and DNA regulation (PURA, YWHAZ). To address the impact of alcohol drinking on AD, studies were conducted using 3xTg-AD mice that express human MAPT, APP, and PSEN-1 transgenes and develop AD-like brain and behavioral pathology. 3xTg-AD and wild-type mice consumed alcohol or saccharin for 4 months. Behavioral tests were administered during a 1-month alcohol-free period. Alcohol intake induced AD-like behavioral pathologies in 3xTg-AD mice including impaired spatial memory in the Morris Water Maze, diminished sensorimotor gating as measured by prepulse inhibition, and exacerbated conditioned fear. Multiplex immunoassay conducted on brain lysates showed that alcohol drinking upregulated primary markers of AD pathology in 3xTg-AD mice: Aβ 42/40 ratio in the lateral entorhinal and prefrontal cortex and total Tau expression in the lateral entorhinal cortex, medial prefrontal cortex, and amygdala at 1-month post alcohol exposure. Immunocytochemistry showed that alcohol use upregulated expression of pTau (Ser199/Ser202) in the hippocampus, which is consistent with late-stage AD. According to the NIA-AA Research Framework, these results suggest that alcohol use is associated with Alzheimer’s pathology. Results also showed that alcohol use was associated with a general reduction in Akt/mTOR signaling via several phosphoproteins (IR, IRS1, IGF1R, PTEN, ERK, mTOR, p70S6K, RPS6) in multiple brain regions including hippocampus and entorhinal cortex. Dysregulation of Akt/mTOR phosphoproteins suggests alcohol may target this pathway in AD progression. These results suggest that nondependent alcohol drinking increases the onset and magnitude of AD-like neural and behavioral pathology in 3xTg-AD mice.

show abstract

Combining lifestyle risks to disentangle brain structure and functional connectivity differences in older adults

Cited by 44 publications

References 67 publications

Resting-state networks in the course of aging—differential insights from studies across the lifespan vs. amongst the old

Resting-state networks in the course of aging—differential insights from studies across the lifespan vs. amongst the old

Alcohol Drinking Exacerbates Neural and Behavioral Pathology in the 3xTg-AD Mouse Model of Alzheimer’s Disease

Alcohol drinking exacerbates neural and behavioral pathology in the 3xTg-AD mouse model of Alzheimer's disease

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