Temporal Cognitive and Brain Changes in Korsakoff Syndrome

Abstract

ObjectiveTo investigate, in Korsakoff patients (KS), cognitive and brain changes over months and up to 10 years after the diagnosis.MethodsTwo groups of 8 KS patients underwent neuropsychological, motor and neuroimaging investigations including structural MRI and 18F-FDG-PET. The KSC group was examined early after the KS diagnosis (KSC-T1) and one year later (KSC-T2). The KSR group was evaluated 10 years after the diagnosis. Longitudinal comparisons in KSC explored short-term changes while cross-sectional comparisons between KSC-T1 and KSR informed about long-term changes.ResultsNo cognitive, motor nor brain deterioration occurred over time in KS patients. There was no clear improvement either, with only modest recovery in the frontocerebellar circuit. Compared to the norms, KSC-T1 had severe episodic memory impairments, ataxia and some executive dysfunctions. They also presented widespread atrophy and hypometabolism, as well as cerebellar hypermetabolism compared to 44 healthy matched controls. Episodic memory remained significantly impaired in KSC-T2 and KSR. Contrary to KSC at T1 and T2, KSR had preserved inhibition abilities. Atrophy was similar but less extended in KSC-T2, and even more limited in KSR. At all times, the thalamus, hypothalamus, and fornix remained severely atrophied. Hypometabolism was still widespread in KSC-T2 and KSR affecting notably the diencephalon. Cerebellar metabolism decreased over time and normalized in KSR, whereas motor dysfunction persisted.ConclusionIn KS, structural and metabolic alterations of the Papez circuit persisted over time, in accordance with the irreversible nature of amnesia. There was neither significant recovery as observed in patients with alcohol use disorder nor progressive decline as in neurodegenerative diseases.

Bifurcating Neurons In The Anterior Thalamic Nuclei

“…The ATN have reciprocal connections with at least three distinct memory structures, namely the medial prefrontal cortex (mPFC), retrosplenial cortex (RSC) and subicular regions of the hippocampal formation (HF) (Bubb et al, 2017;Mathiasen et al, 2017). The importance of the ATN for memory is supported by extensive clinical and experimental evidence (Aggleton, 2008;Aggleton et al, 2016;Barnett et al, 2021;Carlesimo et al, 2011;Dalrymple-Alford et al, 2015;Harding et al, 2000;Kim et al, 2009;Kopelman, 2015;Liu et al, 2021;Maillard et al, 2021;Sweeney-Reed et al, 2021;Wolff et al, 2015). This evidence is consistent with the perspective that the ATN are a critical hub that actively coordinates information processing among telencephalic memory structures (Wolff and Vann, 2019).…”

“…Extensive clinical and experimental evidence supports the conclusion that the anterior thalamic nuclei (ATN) make a significant contribution to memory function (Aggleton, 2008; Aggleton et al, 2016; Barnett et al, 2021; Carlesimo et al, 2011; Dalrymple-Alford et al, 2015; Harding et al, 2000; Kim et al, 2009; Kopelman, 2015; Liu et al, 2021; Maillard et al, 2021; Sweeney-Reed et al, 2021; Wolff et al, 2015). This influence is consistent with the ATN’s strong reciprocal connections with three distinct memory structures, namely the medial prefrontal cortex (mPFC), retrosplenial cortex (RSC) and the hippocampal formation (HF) (Aggleton et al, 2016; Bubb et al, 2017; Mathiasen et al, 2017; Nelson, 2021; Shibata, 1993a, 1993b; van Groen et al, 1999; van Groen and Wyss, 1990; van Groen and Wyss, 1995).…”

Anterior thalamic nuclei: A critical substrate for non-spatial paired-associate memory in rats

“…The pattern of connections suggests that this small brain region is a critical subcortical node that supports episodic memory. This perspective aligns with evidence that loss of ATN neurons in people with the Korsakoff’s syndrome, which is characterised by persistent and severe amnesia, discriminates these patients from alcoholic individuals who retain relatively good memory (Harding, Halliday, Caine, & Kril, 2000; Kopelman, 2015; Maillard et al, 2021). Intra-thalamic recordings in epilepsy patients also reinforce the association between ATN function and memory (Sweeney-Reed et al, 2021).…”

Patients With Severe Alcohol-Related Cognitive Impairment Improve in Flexibility When Abstinence Is Maintained: A Comparative Study With Alzheimer’s Disease

“…Among the few prospective data on the change of cognitive impairment in Wernicke-Korsakoff syndrome or severe ARCI, two studies deserve a specific attention (Fujiwara et al, 2008;Maillard et al, 2021). Regarding the episodic memory impairment, both Fujiwara et al (n = 20) and Maillard et al (n = 8) showed the stability of impairment (Fujiwara et al, 2008;Maillard et al, 2021).…”

“…Among the few prospective data on the change of cognitive impairment in Wernicke-Korsakoff syndrome or severe ARCI, two studies deserve a specific attention (Fujiwara et al, 2008;Maillard et al, 2021). Regarding the episodic memory impairment, both Fujiwara et al (n = 20) and Maillard et al (n = 8) showed the stability of impairment (Fujiwara et al, 2008;Maillard et al, 2021). Regarding the executive functions, the results were discordant and only Fujiwara et al showed a possible improvement in some of the executive functions at follow-up after 2 years, but the patients were abstinent since several years at baseline (Fujiwara et al, 2008).…”