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Recent studies associated rapid eye movement sleep behavior disorder (RBD) in Parkinson’s disease (PD) with severe cognitive impairment and brain atrophy. However, whole-brain functional connectivity has never been explored in this group of PD patients. In this study, whole-brain network-based statistics and graph-theoretical approaches were used to characterize resting-state interregional functional connectivity in PD with probable RBD (PD-pRBD) and its relationship with cognition. Our sample consisted of 30 healthy controls, 32 PD without probable RBD (PD-non pRBD), and 27 PD-pRBD. The PD-pRBD group showed reduced functional connectivity compared with controls mainly involving cingulate areas with temporal, frontal, insular, and thalamic regions ( p  < 0.001). Also, the PD-pRBD group showed reduced functional connectivity between right ventral posterior cingulate and left medial precuneus compared with PD-non pRBD ( p  < 0.05). We found increased normalized characteristic path length in PD-pRBD compared with PD-non pRBD. In the PD-pRBD group, mean connectivity strength from reduced connections correlated with visuoperceptual task and normalized characteristic path length correlated with processing speed and verbal memory tasks. This work demonstrates the existence of disrupted functional connectivity in PD-pRBD, together with abnormal network integrity, that supports its consideration as a severe PD subtype.

BackgroundThe presence of rapid eye movement sleep behavior disorder (RBD) contributes to increase cognitive impairment and brain atrophy in Parkinson’s disease (PD), but the impact of sex is unclear. We aimed to investigate sex differences in cognition and brain atrophy in PD patients with and without probable RBD (pRBD).MethodsMagnetic resonance imaging and cognition data were obtained for 274 participants from the Parkinson's Progression Marker Initiative database: 79 PD with pRBD (PD-pRBD; male/female, 54/25), 126 PD without pRBD (PD-non pRBD; male/female, 73/53), and 69 healthy controls (male/female, 40/29). FreeSurfer was used to obtain volumetric and cortical thickness data.ResultsMales showed greater global cortical and subcortical gray matter atrophy than females in the PD-pRBD group. Significant group-by-sex interactions were found in the pallidum. Structures showing a within-group sex effect in the deep gray matter differed, with significant volume reductions for males in one structure in in PD-non pRBD (brainstem), and three in PD-pRBD (caudate, pallidum and brainstem). Significant group-by-sex interactions were found in Montreal Cognitive Assessment (MoCA) and Symbol Digits Modalities Test (SDMT). Males performed worse than females in MoCA, phonemic fluency and SDMT in the PD-pRBD group.ConclusionMale sex is related to increased cognitive impairment and subcortical atrophy in de novo PD-pRBD. Accordingly, we suggest that sex differences are relevant and should be considered in future clinical and translational research.

Background and Objectives: Although several meta-analyses have evaluated the effects of motor imagery (MI) on upper-limb recovery using the Fugl-Meyer Assessment for the Upper Extremity (FM-UE), evidence based on more specific (Action Research Arm Test, ARAT) and functional (Barthel Index, BI) outcomes remains scarce. This study examined the effect of MI combined with conventional rehabilitation therapy (CRT), which translates into meaningful improvements in upper-limb performance and functional independence after stroke, accounting for methodological quality and publication bias. Materials and Methods: A systematic review and meta-analysis were carried out in accordance with PRISMA recommendations, with prior registration in PROSPERO (CRD420251120044). Comprehensive searches were conducted across six electronic databases up to July 2025. The methodological rigor of the included studies was evaluated using the PEDro scale, and risk of bias was appraised with the Cochrane RoB 2 instrument. Random-effects models estimated pooled effect sizes (ESs) for the ARAT and BI, alongside analyses of heterogeneity, publication bias, and moderators. Results: Eleven RCTs (n = 425) were included. A small pooled improvement in ARAT was observed (ES = 0.25; 95% CI: 0.13–0.37; p < 0.001); however, this effect was rendered non-significant after correction for publication bias (ES = 0.08; 95% CI: −0.14–0.31). No significant differences were found for the BI (ES = 0.41; 95% CI: −0.35–1.18; p = 0.268), with substantial heterogeneity (I2 = 96.6%). The mean PEDro score was 6.6, indicating moderate methodological quality. Conclusions: MI combined with CRT yields small and inconsistent effects on upper-limb recovery and no improvement in functional independence. Current evidence does not support its routine use in stroke rehabilitation. Well-designed, adequately powered randomized controlled trials employing standardized MI protocols are required to determine its true clinical relevance.

Background and objective: Brain atrophy and cognitive impairment in neurodegenerative diseases are influenced by sex. We aimed to investigate sex differences in brain atrophy and cognition in de novo Parkinson’s disease (PD) patients. Methods: Clinical, neuropsychological and T1-weighted MRI data from 205 PD patients (127 males:78 females) and 69 healthy controls (40 males:29 females) were obtained from the PPMI dataset. Results: PD males had a greater motor and rapid eye movement sleep behavior disorder symptomatology than PD females. They also showed cortical thinning in postcentral and precentral regions, greater global cortical and subcortical atrophy and smaller volumes in thalamus, caudate, putamen, pallidum, hippocampus, and brainstem, compared with PD females. Healthy controls only showed reduced hippocampal volume in males compared to females. PD males performed worse than PD females in global cognition, immediate verbal recall, and mental processing speed. In both groups males performed worse than females in semantic verbal fluency and delayed verbal recall; as well as females performed worse than males in visuospatial function. Conclusions: Sex effect in brain and cognition is already evident in de novo PD not explained by age per se, being a relevant factor to consider in clinical and translational research in PD.

Introduction Olfactory deficits, especially in odor identification (OID), have been linked to Alzheimer’s disease (AD), likely due to regional proteinopathy and atrophy in the olfactory brain circuit. Their cognitive and biological correlates across the clinical spectrum, particularly in individuals with no evident cognitive impairment, have been underexplored. This examination is relevant because many individuals of this group will not progress to dementia, and olfactory deficits may reflect ongoing pathological processes and could enrich risk stratification. Methods We analyzed data from a cohort of 233 subjective cognitive impairment (SCI, n =152), mild cognitive impairment (MCI, n =50), and AD dementia ( n =31) individuals from the Karolinska University Hospital Memory Clinic (Solna, Sweden). We examined the association of performance on the 16-item Sniffin’ Sticks OID test (free and total [free or cued] identification scores) with a range of markers: cognitive performance, cerebrospinal fluid biomarkers, AD- and olfactory-related brain volumes, and white matter hyperintensities volume. We performed correlation analyses, generalized additive models, and threshold regressions, adjusted for sociodemographic factors and APOE status. Results OID performance was better in SCI compared to MCI and AD. Aβ42/40 ratio was positively associated with OID in SCI and AD, with APOE ε4 carriers driving this association in SCI. Hippocampal volume was positively associated with OID in AD. Higher volume of white matter hyperintensities was negatively associated with OID in MCI. The relationships of OID with Aβ42/40 and hippocampal volume were linear in the whole cohort. Worse verbal episodic memory performance was associated with lower OID scores only in the AD group. Free OID showed a broader and stronger pattern of associations with episodic memory and biomarkers compared with total OID. Threshold regression between free OID and Aβ42/40 identified a subthreshold value (<0.94) above the clinical cutoff (<0.86), capturing nine non-demented individuals within the gray zone between these cutoffs. Conclusions Our findings support an association between amyloid levels and olfactory performance in the AD spectrum, underscoring the potential of smell tests as cost-effective tools in multimodal stratification frameworks. In dementia stages, medial temporal atrophy accompanied by memory impairment may be the main correlate of olfactory deficits.

Introduction Longitudinal subtypes in Alzheimer’s disease (AD) have been identified based on their distinct brain atrophy trajectories, encompassing mediotemporal and cortical pathways. These subtypes include minimal atrophy, limbic predominant, limbic predominant plus, diffuse atrophy and hippocampal sparing. The impact of sex on the progression of these subtypes remains a crucial area of investigation. Methods We analysed MRI data from 320 amyloid-β positive individuals with AD from three international cohorts (ADNI, J-ADNI and AIBL). Longitudinal clustering was conducted to identify atrophy trajectories over eight years from the clinical disease onset, with separate trajectories delineated for women and men. Results Women consistently exhibited earlier hippocampal atrophy and a higher burden of white matter abnormalities compared to men, yet women displayed less cognitive decline over time. Additionally, specific risk factors and distinct neuropsychiatric symptoms were associated with sex within specific trajectories. Conclusions AD subtypes show sex-specific differences in disease progression, highlighting the need to account for these differences from the early disease stages. Integrating imaging biomarkers with sex differences can enable the identification of more precise treatments for each patient, ensuring that both women and men have equal access to tailored care.

Background: Motor imagery (MI) and mirror therapy (MT) are widely used neurorehabilitation strategies to enhance motor recovery after stroke and are commonly applied as adjuncts to conventional rehabilitation therapy (CRT). However, direct comparative evidence between these interventions remains limited. This systematic review compared the effects of MI and MT on motor function, functional performance, spasticity, and gait-related outcomes in adults after stroke. Methods: A systematic comparative review with narrative synthesis was conducted following PRISMA guidelines and registered in PROSPERO (CRD420251274308). PubMed, Cochrane Library, CINAHL, Scopus, Web of Science, and ScienceDirect were searched up to July 2025. Clinical trials directly comparing MI and MT in adults with stroke were included. Methodological quality was assessed using the PEDro scale, and risk of bias was evaluated with the Cochrane RoB 2 tool. Results: Six clinical trials involving 206 participants were included. Both MI and MT were associated with significant pre–post improvements across motor function, functional performance, spasticity, and gait-related outcomes. Between-group comparisons yielded heterogeneous findings, with no consistent evidence supporting the superiority of either intervention. Isolated advantages of MI were reported for specific upper-limb subdomains, but these effects were not consistently replicated. Overall methodological quality ranged from low to moderate, and all included studies were judged to be at high risk of bias according to the RoB 2 tool. Conclusions: MI and MT appear to provide comparable benefits for motor and functional recovery after stroke when used as adjuncts to CRT. Current evidence does not support the preferential use of one intervention, highlighting the need for well-designed trials with improved methodological rigor.

[This corrects the article DOI: 10.3389/fnagi.2025.1539508.].

The mechanisms underlying olfactory decline in aging need further investigation. Noticeably, the longitudinal relationship of biological markers with olfaction remains underexplored. We investigated whether baseline levels and progression of microvascular lesions and brain atrophy are associated with odor identification (OID) decline. The association between structural MRI markers and OID decline was examined in participants from the SNAC-K MRI study who were free from dementia at baseline (  = 401, mean age = 70.2 years, 60% females). OID was repeatedly assessed over 15 years. Presence of lacunes, white matter hyperintensities (WMH), perivascular spaces (PVS), and lateral ventricular, hippocampal, amygdalar, and total gray matter (GM) volumes were assessed up to 6 years, concurrent with the first 6 years of olfactory assessments. Higher PVS count and lower hippocampal and GM volumes at baseline were associated with accelerated OID decline (  < 0.05). Longitudinally (  = 225), presence of lacunes at follow-up, faster WMH volume and PVS count increases, faster lateral ventricular enlargement, and faster hippocampal, amygdalar, and GM atrophy were associated with accelerated OID decline (  < 0.05). Olfactory decline is related to both increased cerebrovascular burden and accelerated brain atrophy over time.

Rapid eye movement sleep behavior disorder (RBD) is associated with high likelihood of prodromal Parkinson’s disease (PD) and is common in de novo PD. It is associated with greater cognitive impairment and brain atrophy. However, the relation between structural brain characteristics and cognition remains poorly understood. We aimed to investigate subcortical and cortical atrophy in de novo PD with probable RBD (PD-pRBD) and to relate it with cognitive impairment. We analyzed volumetry, cortical thickness, and cognitive measures from 79 PD-pRBD patients, 126 PD without probable RBD patients (PD-non pRBD), and 69 controls from the Parkinson’s Progression Markers Initiative (PPMI). Regression models of cognition were tested using magnetic resonance imaging measures as predictors. We found lower left thalamus volume in PD-pRBD compared with PD-non pRBD. Compared with controls, PD-pRBD group showed atrophy in the bilateral putamen, left hippocampus, left amygdala, and thinning in the right superior temporal gyrus. Specific deep gray matter nuclei volumes were associated with impairment in global cognition, phonemic fluency, processing speed, and visuospatial function in PD-pRBD. In conclusion, cognitive impairment and gray matter atrophy are already present in de novo PD-pRBD. Thalamus, hippocampus, and putamen volumes were mainly associated with these cognitive deficits.