Quantitative neurobiological evidence for accelerated brain aging in alcohol dependence

Guggenmos, Matthias; Schmack, Katharina; Sekutowicz, Maria; Garbusow, Maria; Sebold, Miriam; Sommer, Christian; Smolka, Michael N.; Wittchen, Hans‐Ulrich; Zimmermann, U.; Heinz, Andreas; Sterzer, Philipp

doi:10.1038/s41398-017-0037-y

Cited by 68 publications

(58 citation statements)

References 25 publications

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“…A recent voxel-based structural analysis measured gray matter volumes in 110 brain regions in those with AUD and controls aged 25 to 65 years to examine for potential alcohol-related accelerated aging. Results indicated that, in the later decades of life, the brain age of the chronic drinkers was increased by an impressive 12 years, consistent with the accelerated brain aging theory in substance users (Guggenmos et al, 2017). Similarly, we recently compared cortical and subcortical volumes in nonsmokers and smokers aged 22 to 70 years without any other substance use disorder and also found chronic smoking associated with accelerated age-related volume loss in subcortical white and gray matter regions, including the cerebellum (Durazzo et al, 2017).…”

supporting

confidence: 70%

Cerebellar Morphometry and Cognition in the Context of Chronic Alcohol Consumption and Cigarette Smoking

Cardenas

Hough

Durazzo

et al. 2019

Alcoholism Clin & Exp Res

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Background: Cerebellar atrophy (especially involving the superior-anterior cerebellar vermis) is among the most salient and clinically significant effects of chronic hazardous alcohol consumption on brain structure. Smaller cerebellar volumes are also associated with chronic cigarette smoking. The present study investigated effects of both chronic alcohol consumption and cigarette smoking on cerebellar structure and its relation to performance on select cognitive/behavioral tasks. Methods: Using T1-weighted Magnetic Resonance Images (MRIs), the Cerebellar Analysis Tool Kit segmented the cerebellum into bilateral hemispheres and 3 vermis parcels from 4 participant groups: smoking (s) and nonsmoking (ns) abstinent alcohol-dependent treatment seekers (ALC) and controls (CON) (i.e., sALC, nsALC, sCON, and nsCON). Cognitive and behavioral data were also obtained. Results: We found detrimental effects of chronic drinking on all cerebellar structural measures in ALC participants, with largest reductions seen in vermis areas. Furthermore, both smoking groups had smaller volumes of cerebellar hemispheres but not vermis areas compared to their nonsmoking counterparts. In exploratory analyses, smaller cerebellar volumes were related to lower measures of intelligence. In sCON, but not sALC, greater smoking severity was related to smaller cerebellar volume and smaller superior-anterior vermis area. In sALC, greater abstinence duration was associated with larger cerebellar and superior-anterior vermis areas, suggesting some recovery with abstinence. Conclusions: Our results show that both smoking and alcohol status are associated with smaller cerebellar structural measurements, with vermal areas more vulnerable to chronic alcohol consumption and less affected by chronic smoking. These morphometric cerebellar deficits were also associated with lower intelligence and related to duration of abstinence in sALC only.

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supporting

confidence: 70%

Cerebellar Morphometry and Cognition in the Context of Chronic Alcohol Consumption and Cigarette Smoking

Cardenas

Hough

Durazzo

et al. 2019

Alcoholism Clin & Exp Res

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“…The identification of brain systems from a population-based cohort that is not suffering from any other psychiatric illness has major advantages: By identifying subclinical correlates of psychiatric illness, prior to the full manifestation of disorder, it is possible to avoid the potential impact of effects indirectly related to illness, such as substance use and medication effects. For example, 17% percent of the schizophrenia, and 21% percent of the Bipolar samples but none of the healthy controls studied here have a history of alcohol abuse, which has been linked to widespread decreases in grey matter 40 . In addition, various psychiatric medicines, including lithium, which is often prescribed to Bipolar patients, have also been linked to alterations in grey matter volume , it is possible that lithium-induced increases in grey matter volume may have contributed to the observed absence of significant findings in Bipolar patients in this study.…”

Section: Discussionmentioning

confidence: 80%

Identification of neurobehavioural symptom groups based on shared brain mechanisms

Ing¹,

Sämann²,

Chu³

et al. 2019

Nat Hum Behav

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Most psychopathological disorders develop in adolescence. The biological basis for this development is poorly understood. To enhance diagnostic characterisation, and develop improved targeted interventions, it is critical to identify behavioural symptom groups that share neural substrates. We ran analyses to find relations between behavioral symptoms, and neuroimaging measures of brain structure and function in adolescence. We found two symptom groups, consisting of anxiety/depression and executive dysfunction symptoms respectively, which correlated with distinct sets of brain regions and interregional connections, measured by structural and functional neuroimaging modalities. We found that the neural correlates of these symptom groups were present before behavioural symptoms had developed. These neural correlates showed case-control differences in corresponding psychiatric disorders, depression and ADHD, in independent clinical samples. By characterising behavioral symptom groups based on shared neural mechanisms, our results provide a framework for developing a classification system for psychiatric illness, which is based on quantitative neurobehavioural measures.

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“…Similarly, so-called "blackout" episodes, commonly associated with drinking large amounts of alcohol over short periods of time (Goodwin, Crane & Guze, 1969;White, 2003), are clearly largely defined by and associated with AA (White, 2003;Nelson et al, 2004;Perry et al, 2006), appearing to involve both the frontal lobe and hippocampal regions (White, 2003;Oscar-Berman et al, 2004;Alderazi & Brett, 2007;Vetreno, Hall & Savage, 2011;Wetherill, Schnyer & Fromme, 2012;Hermens & Lagopoulos, 2018). In particular, chronic alcoholism appears to act synergistically with the normal ageing process to exacerbate the memory and other cognitive deficits commonly resulting from the latter (Pfefferbaum et al, 1992;Kim et al, 2012;Sabia et al, 2014;Guggenmos et al, 2017;Rehm et al, 2019).…”

Section: Basal Forebrain Damage In Ad and Arbdmentioning

confidence: 99%

A lipid-leakage model for Alzheimer’s Disease

Rudge

2019

Preprint

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This paper describes a potential new explanation for Alzheimer’s disease (AD), referred to here as the lipid-leakage model. It proposes that AD is caused by the influx of lipids following the breakdown of the blood brain barrier (BBB). The model argues that a principle role of the BBB is to protect the brain from external lipid access. When the BBB is damaged, it allows a mass influx of (mainly albumin-bound) free fatty acids (FFAs) and lipid-rich lipoproteins to the brain, which in turn causes neurodegeneration, amyloidosis, tau tangles and other AD characteristics. The model also argues that, whilst β-amyloid causes neurodegeneration, as is widely argued, its principal role in the disease lies in damaging the BBB. It is the external lipids, entering as a consequence, that are the primary drivers of neurodegeneration in AD., especially FFAs, which induce oxidative stress, stimulate microglia-driven neuroinflammation, and inhibit neurogenesis. Simultaneously, the larger, more lipid-laden lipoproteins, characteristic of the external plasma but not the CNS, cause endosomal-lysosomal abnormalities, amyloidosis and the formation of tau tangles, all characteristic of AD. In most cases (certainly in late-onset, noninherited forms of the disease) amyloidosis and tau tangle formation are consequences of this external lipid invasion, and in many ways more symptomatic of the disease than causative. In support of this, it is argued that the pattern of damage caused by the influx of FFAs into the brain is likely to resemble the neurodegeneration seen in alcohol-related brain damage (ARBD), a disease that shows many similarities to AD, including the areas of the brain it affects. The fact that neurodegeneration is far more pronounced in AD than in ARBD most likely results from the greater heterogeneity of the lipid assault in AD compared with ethanol alone. The lipid-leakage model, described here, arguably provides the first cohesive, multi-factorial explanation of AD that best accounts for all currently known major risk factors, and credibly explains all AD-associated pathologies, including those, such as endosomal-lysosomal dysfunction and excessive lipid droplet formation, that have been too readily overlooked by other accounts of this disease.

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Quantitative neurobiological evidence for accelerated brain aging in alcohol dependence

Cited by 68 publications

References 25 publications

Cerebellar Morphometry and Cognition in the Context of Chronic Alcohol Consumption and Cigarette Smoking

Cerebellar Morphometry and Cognition in the Context of Chronic Alcohol Consumption and Cigarette Smoking

Identification of neurobehavioural symptom groups based on shared brain mechanisms

A lipid-leakage model for Alzheimer’s Disease

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