Giovanna Bubbico

Background: Foreign language learning (FLL) in older adults is a cognitive training tool that enhances neuroplasticity and supports cognitive reserve. While its impact on cortical networks is well‐documented, little is known about its effects on subcortical structures, particularly the cerebellum. Given its role in learning and aging, we hypothesize that FLL selectively modulates cerebellar‐cortical connectivity, with changes in connectivity overlapping with regions rich in CB1 and GABAa receptor expression. Methods: We conducted a resting‐state functional connectivity (rs‐FC) MRI study on 27 older adults randomly assigned to either a four‐month FLL intervention ( n = 14) or a control group ( n = 13). We performed seed‐based analyses of cerebellar subregions using voxel‐wise comparisons to identify FLL‐induced connectivity changes. Additionally, we examined spatial correlations between these changes and receptor expression maps from publicly available databases. Results: The FLL group exhibited significant alterations in cerebellar‐cortical connectivity. Specifically, Crus I showed decreased connectivity with the posterior cingulate cortex, while Lobule VI exhibited increased connectivity with the superior frontal cortex. Additionally, Vermis IX showed reduced connectivity with the occipital cortex. These connectivity changes spatially overlapped with the distribution of CB1 receptors in Lobule VI and GABAa receptors in Vermis IV‐V. Conclusion: Our findings highlight the role of the cerebellum in the neural adaptations associated with FLL in older adults. The observed connectivity changes suggest a link between FLL‐induced neuroplasticity and the distribution of CB1 and GABAa receptors, shedding light on potential molecular mechanisms underlying cognitive resilience in aging.

Substance Use Disorders (SUDs) are frequently associated with impairments in emotional regulation and behavioural control. Among the most prevalent substances of abuse, alcohol and cocaine are known to exert distinct effects on neuropsychological functioning. This study aimed to compare individuals with Alcohol Use Disorder (AUD) and Cocaine Use Disorder (CUD) in terms of impulsivity and alexithymia, and to examine the clinical implications of poly-substance use involving both alcohol and cocaine. Participants completed standardized psychometric assessments, including the Barratt Impulsiveness Scale (BIS-11), the Brief Psychiatric Rating Scale (BPRS), and the Toronto Alexithymia Scale (TAS-20). Group comparisons were conducted using non-parametric tests, and logistic regression models were applied to control for demographic covariates. The findings showed that impulsivity levels were comparable across groups, whereas alexithymia scores were significantly higher in individuals with AUD and in those with poly-substance use, relative to CUD-only participants. These findings underscore the relevance of targeting emotional regulation difficulties, particularly alexithymia, in the assessment and treatment of SUDs. Integrating emotion-focused interventions may enhance treatment outcomes, especially for individuals with co-occurring substance use patterns. Future research is needed to clarify the underlying neuropsychological mechanisms contributing to these differences and to inform more personalized approaches to addiction care.

Objective Bilingualism has been associated with cognitive benefits and a potential protective effect against neurodegenerative conditions. Previous research has shown that bilingual individuals exhibit greater white matter integrity compared to monolinguals of the same age. However, the impact of foreign-language learning on brain structure in older adults during the initial stages of language acquisition remains uncertain. This study aimed to investigate the cognitive and structural effects of a four-month-long foreign language learning program in a group of healthy monolinguals older adult. Materials and Methods Thirteen Italian-speaking participants (aged 59-78) underwent a four-month intensive English course for beginners. Pre- and post-assessments were conducted to evaluate executive cognitive functions, as well as diffusion tensor imaging (DTI) to examine brain structural changes. Results The study findings showed substantial increases in axial, radial, and mean diffusivity during the four-month language learning period. The most prominent variations were observed in key brain regions, namely the fronto-occipital fasciculus, the superior longitudinal fasciculus, and the corpus callosum areas. Notably, brain-behaviour correlations indicated a robust positive relationship between changes in axial diffusivity and performance on the Stroop task, a well-established measure of cognitive interference inhibition. Conclusions These findings suggest that a four-month foreign language learning program can lead to structural changes in the brain, particularly affecting white matter integrity and that these structural changes are associated with improvements in executive functions. The study underscores the potential of brief language learning interventions to influence brain structure and enhance cognitive abilities in older adults. Highlights Bilingualism is associated with cognitive advantages and the potential for protection against neurodegenerative conditions, as evidenced by bilingual individuals displaying enhanced white matter integrity compared to individuals who are monolingual and of the same age. The study investigates how a four-month foreign language learning program affects brain structure in older adults during the initial stages of language acquisition The research reveals significant increases in axial, radial, and mean diffusivity in key brain regions, including the fronto-occipital fasciculus, superior longitudinal fasciculus, and corpus callosum, during the language learning period. The study demonstrates a positive link between changes in axial diffusivity and performance on the Stroop task, indicating that short language learning interventions can lead to structural brain changes associated with improved executive functions in older adults.

Background: There is an urgent need for accessible biomarkers that can predict cognitive impairment in older individuals. There is also a complete lack of biomarkers for TAR DNA‐binding protein‐43 (TDP‐43), a frequent and important neurodegenerative pathology in older individuals, currently referred to as Limbic‐predominant Age‐related TDP‐43 Encephalopathy‐Neuropathologic Change (LATE‐NC). Here we explored the utility of linguistic markers for prediction of future cognitive impairments and LATE‐NC.Method: 134 participants of the Leisure World cohort, an epidemiologic study in a California retirement community, produced written descriptions of the cookie‐theft picture from the Boston Aphasia Diagnostic Examination. All had normal cognition at the time. Samples were quantitatively analyzed for 31 linguistic markers (see table 1 for definitions of select relevant variables). Participants subsequently joined the 90+ study and underwent cognitive assessments every 6 months and autopsy after death. Cognitive impairment and its onset date were determined at postmortem conferences. LATE‐NC was considered present in those with TDP‐43 in hippocampus or neocortex, and Alzheimer’s disease neuropathologic change (ADNC) in those with high likelihood ADNC according to NIA‐ AA guidelines. To examine the relationships between linguistic markers and future cognitive impairment and presence of LATE‐NC and ADNC, we used logistic regression analysis. Models were adjusted for sex, education, age at the time of writing the samples and age at death.Result: Table 2 summarizes demographic and neuropathology findings. Additionally, mean age at cognitive impairment was 93.2 in 72% who developed cognitive impairment. Future cognitive impairment was significantly associated with less information content (OR:0.02) and fewer clauses (OR:0.93) (Table 3). Also, presence of LATE‐NC was significantly associated with higher proportions of content words (OR:7.2), higher proportion of function word errors (OR:10.5), and fewer complete units (OR:0.15). Lower number of words also trended towards a significant association (OR:8, p = 0.07) with LATE‐NC. No language measure was associated with ADNC.Conclusion: Our results suggest that linguistic markers derived from writing samples obtained on average 8 years prior to development of cognitive impairment and 12 years before death might serve as biomarkers for future cognitive impairment and presence of LATE‐NC at autopsy.

Background: Subjective cognitive decline (SCD) is a state in which a subjectively perceived decline in cognition appears in the absence of an objective decline detected by neuropsychological tests. It tends to occur at the late phase of preclinical AD and has been proposed as a pre‐MCI stage (Rabin et al., 2017). Hippocampal atrophy is a well‐known feature of AD (Halliday, 2017).Method: Brain morphometry was observed in a 2‐years follow‐up. Participants were assigned to the SCD or non‐SCD group according to the SCD research criteria: SCD‐Q score ≥7 was classified as SCD (Rami et al., 2014). Among seventy community‐ dwelling individuals who had been enrolled at baseline (Lauriola et al., 2017), thirty‐five (64.6 ±5.6 y, 15M/20F) took‐part in the follow‐up phase. All participants underwent complete neuropsychological battery and a 3T Structural Magnetic Resonance Imaging (MRI) examination (Philips Achieva X Series). High‐resolution structural images were acquired through a 3D magnetization‐prepared rapid acquisition gradient echo sequence: matrix 256 × 256, field of view 240 × 240 × 170 mm, slice thickness 1 mm, no gaps, in‐plane voxel size 1 mm × 1 mm, flip angle 12°, repetition time = 8.2 ms, echo time = 3.8 ms. Structural T1‐weighted images were processed using FSL software (https://fsl.fmrib.ox.ac.uk/fsl/fslwiki, version 6.0). Gray matter differences were assessed with VBM (voxel‐based morphometry), as implemented in FSL (FMRIB Software Library v6.0).Result: Significant differences (p=0.03, corrected for multiple comparison) were observed between SCD and non‐SCD partecipants in the hippocampus global total intracranial normalized volume (TIV). Atrophy maps on hippocampal areas showed major involvement of the para‐hippocampal region, of the left mesial temporal lobe (Fig. 1).Conclusion: SCD hippocampal volumetry reduction might be considered a negative prognostic finding as a potential prelude to an evolution in early dementia.

Corrigendum: Effects of Second Language Learning on the Plastic Aging Brain: Functional Connectivity, Cognitive Decline, and Reorganization