Introduction:Antibodies to the extracellular domain of the astrocytic aquaporin-1 (AQP-1) have been reported in patients with neuromyelitis optica spectrum disorder (NMOSD) and a few multiple sclerosis (MS) patients with predominant spinal cord involvement. Our aim was to identify the prevalence and clinical correlates of antibodies against AQP1 (AQP1-Abs) in a broader spectrum of autoimmune inflammatory demyelinating central nervous system (CNS) disorders. Methods:Sera from patients with NMOSD (n=30), recurrent inflammatory optic neuropathy (RION) (n=15), relapsing remitting MS (RRMS) (n=69), of which 10 had optic neuritis and/or short myelitis, and healthy controls (n=36) were screened for the presence of AQP1-Abs by ELISA and for antibodies against aquaporin-4 (AQP4-Abs) and myelin oligodendrocyte glycoprotein (MOG)-Abs by cell-based assays. Results:AQP1-Abs were found in 11% of patients with optic neuritis and/or myelitis [6.7% of NMOSD, 13.3% of RION and 20% of RRMS with optic neuritis and/or short myelitis]. None of the RRMS patients without optic neuritis and/or short myelitis and none of the healthy controls had AQP1-Abs. The two AQP1-Abs-positive RRMS patients, who fulfilled Barkhof criteria by virtue of MRI lesion distribution, had experienced ≥4 short myelitis and/or optic neuritis attacks. Conclusion:AQP1-Abs are occasionally detected in autoimmune inflammatory demyelinating CNS disorders highlighting optic nerve and spinal cord involvement.

Cerebrovascular reactivity (CVR) reflects the ability of cerebral vessels to adapt to metabolic demands and may be impaired in multiple sclerosis (MS). Its clinical relevance in relapsing–remitting MS (RRMS), particularly in relation to disability and cognition, remains uncertain. We compared CVR, quantified by the Breath-Holding Index (BHI), between patients with RRMS and healthy controls, and examined its associations with neurological disability and cognitive performance. In this cross-sectional observational study consecutive RRMS patients and age- and sex-matched healthy controls (2:1 ratio) were enrolled. CVR to hypercapnia was assessed by transcranial Doppler using BHI. Cognitive performance was evaluated with the Brief International Cognitive Assessment for MS battery, and neurological disability with the Expanded Disability Status Scale (EDSS). Multivariable linear regression was used for adjusted analyses. Ninety patients with RRMS and 45 healthy controls were included. BHI was lower in RRMS than in controls (0.88 ± 0.13 vs. 1.13 ± 0.13), with a mean difference of − 0.256 (95

Background/Objectives: Multiple Sclerosis (MS) is a chronic disease with significant clinical and radiological heterogeneity. This fact, together with the increased number of disease-modifying treatments available, poses challenges in the therapeutic decisions and for the overall management of the disease. In this study, an expert panel on MS from Greece aimed to formulate a consensus, in order to provide recommendation on disease-modifying treatment (DMT) initiation and switching, as well as de-escalation strategies in Relapsing MS (RMS). Methods: The study followed two-round voting based on a modified Delphi setting. A questionnaire was constructed by a subgroup of five experts (core group) and was subsequently administered in a printed form to a group of 12 MS experts in total (panel) in a face-to-face meeting. Consensus required at least 80% agreement within the panel in order to signify strong consensus. Results: The panel agreed that the overall therapeutic plan (DMT choice) must take into consideration the degree of disease activity (low/moderate/high). In certain cases with suboptimal response to a moderate-efficacy DMT, a horizontal switch to another moderate-efficacy DMT may be a valid strategy. However, in cases exhibiting disability accumulation, therapy escalation should be preferred. The concept of de-escalation was suggested as an alternative strategy for cases with stable disease receiving a high-efficacy long-term DMT in the long term. Due to the possibility of rebound phenomena with certain medications (such as fingolimod and natalizumab), a bridging strategy could be applied in cases of family planning and drug-related adverse events (such as lymphopenia and hepatotoxicity), especially in PwMS with recent inflammatory activity. Conclusions: Although novel biomarkers may soon help clinicians predict future disability accumulation, currently, regular and detailed patient monitoring seems to be the optimal way to guide clinicians’ decisions on treatment changes.

Neurogenic bladder (NGB) is one of the most common and debilitating manifestations of multiple sclerosis (MS), substantially impairing quality of life and increasing the risk of secondary complications. To determine the pooled prevalence of NGB and its subtypes in people with MS (PwMS). A systematic review and meta-analysis was conducted in accordance with PRISMA and MOOSE guidelines and was prospectively registered in PROSPERO. The MEDLINE, Embase, Scopus, and Google Scholar databases were searched. Risk of bias was assessed using the ROBINS-E scale. Pooled prevalence estimates were calculated using a random-intercept generalized linear mixed model (GLMM) with logit transformation and Hartung-Knapp adjustment. Meta-regression and subgroup analyses were performed to explore heterogeneity, and sensitivity analyses included leave-one-out analysis and prediction intervals. Twenty-two studies comprising 39,304 PwMS were included. The pooled prevalence of NGB was 48.8

Background/Objectives: Multiple sclerosis (MS)-related optic neuritis (ON) results in thinning of the peripapillary nerve fiber layer (pRNFL) which tends to be temporal quadrant-predominant. Optical coherence tomography angiography (OCTA) enables visualization of the retinal vasculature. Prior studies have shown reduced peripapillary vessel density (VD) in MS but data on the quadrantic pattern of peripapillary VD loss are limited. Our objective was to investigate the pattern of OCTA-derived peripapillary VD reduction in MS. Methods: People with MS (PwMS) and healthy controls (HC) underwent optic disc OCTA scans (Solix, Optovue) and VD was derived for the peripapillary region and quadrants. Eyes with ON within six months were excluded. Analyses were performed with generalized estimating equations models and standardized coefficients are presented. Results: We included 50 eyes from 29 PwMS (12 ON, 38 non-ON) and 12 eyes from 6 HC. VD in the peripapillary region was lower in MS ON eyes compared to HC with the largest effect size observed in the temporal quadrant (average: -1.47, p < 0.001; superior: -1.08, p = 0.006; inferior: -0.94; p = 0.017; temporal: -1.55; p < 0.001; nasal: -1.06, p = 0.007). In MS non-ON eyes, only temporal VD was significantly lower compared to HC eyes (temporal: -0.77, p = 0.004). Moderate to strong correlations were observed between OCT and corresponding OCTA metrics from the same regions. Conclusions: Our findings suggest that vascular alterations in the peripapillary region may exhibit a temporal quadrant predominant pattern. Larger studies are needed to further characterize the patterns and temporal evolution of retinal peripapillary vascular injury in MS.

Introduction:Anemia appears as a common comorbidity in a different timing and underlying pathophysiology in people with MS (PwMS) and has been proposed as a prodrome finding in MS. This systematic review and meta-analysis aims to fulfill the need to clarify some characteristics of anemia in PwMS. Methods:A systematic literature search was performed using the MEDLINE PubMed, Scopus, and Google Scholar databases. Eligible studies underwent quality assessment using the Robins-E, and a meta-analysis of proportion was performed. The risk of anemia in PwMS versus healthy controls was calculated based on a subset of case-control studies. Reliability and robustness were assessed using leave-one-out analysis. Results:In a pool of 143,879 PwMS across 21 studies, anemia had a pooled prevalence of 12.5% (95% CI [8.1%, 17.7%], I 2  = 99.0%, p Q  = 0). In a subset of five studies, the relative risk of anemia between PwMS and healthy controls was 2.9 (95% CI [1.45, 5.79], I 2 = 97.6%, p z  = 0.002, p Q  < 0.001) in favor of PwMS. Conclusion:The intersection between anemia and MS presents a complex, multifaceted clinical challenge due to several pathophysiological mechanisms and DMT-related interactions. Further structured studies are needed to evaluate the exact underlying mechanisms and the directionality of this relationship.

INTRODUCTION:Pregnancy in multiple sclerosis (MS) is associated with reduced relapse activity, though the postpartum period carries a heightened risk of disease reactivation. Continuation of natalizumab late gestation has been proposed to mitigate this rebound effect and maintain disease stability. METHODS:This retrospective study included 62 women with MS with initial pregnancy plans. Of those 32 continued natalizumab infusion until the 34th week of gestation and 30 discontinued natalizumab treatment upon confirmation of pregnancy. Participants were assessed pre- and within three months postpartum for disability status (EDSS), relapse occurrence, and MRI activity (presence of gadolinium-enhancing [GdE + ] lesions). Neonatal anthropometric parameters (birth weight, length, head circumference) were also recorded. RESULTS:Within the natalizumab group, outcomes improved from baseline (last preconception assessment) to the postpartum follow-up (≤3 months after delivery) with lower EDSS scores (p = 0.003), marked reductions in relapse frequency and GdE + lesions (p < 0.001 for both). The non-natalizumab group showed smaller reductions in relapse rates and no significant change in MRI activity. Between-group comparisons at postpartum follow-up revealed lower EDSS scores (p = 0.028), fewer relapses (p = 0.029), and fewer GdE + lesions (p = 0.001) in the natalizumab group. Neonatal anthropometric parameters did not differ significantly between groups and WHO Child Growth Standards (p > 0.05). CONCLUSIONS:Continuing natalizumab treatment until late pregnancy was associated with better postpartum clinical and radiological outcomes. Neonatal anthropometric measures were comparable to reference child growth standards. These findings support that late pregnancy natalizumab continuation may be a viable high efficacy strategy for women with highly active MS.

Serum neurofilament light chain (sNfL) has emerged as a biomarker reflecting neuroaxonal damage. The role of sNfL in predicting clinical outcome and guiding therapeutic management in multiple sclerosis (MS) is an ongoing research topic. We sought to evaluate sNfL utility for the prediction of achieving No Evidence of Disease Activity-3 (NEDA-3) among MS patients. We conducted a prospective cohort study including MS patients with a single sNfL measurement at first clinical evaluation. Follow-up was performed every 6 months/clinical relapse and included clinical and MRI evaluation. The main outcome was NEDA-3 achievement during follow-up. sNfL levels were measured, using single-molecule-array (SIMOA) assay. sNfL age- and BMI-normalized Z-scores > 1.5 were defined as high. Linear regression analyses were performed to identify predictors of baseline sNfL Z-score and multivariable Cox proportional hazard regression models were used to evaluate predefined outcomes. We included 125 patients [age at sNfL measurement:40 ± 12, 30

Dyslipidemia remains a major, modifiable determinant of global stroke burden, accounting for more than one-fifth of ischemic strokes (IS) worldwide. Recent evidence has shifted emphasis from conventional lipid fractions to apolipoprotein B (ApoB)-containing lipoproteins, including lipoprotein(a) [Lp(a)], which more accurately reflect atherogenic particle burden than low-density lipoprotein cholesterol (LDL-C) alone and are increasingly used for stroke risk stratification. While the principle "the faster and the lower, the better" underpins dyslipidemia management, evidence-based, subtype-specific lipid strategies in stroke remain limited. Intensive LDL-C reduction significantly lowers recurrent IS risk; however, uniform lipid targets are often applied without accounting for stroke etiology. High-intensity statins remain first-line therapy, with pleiotropic benefits extending beyond LDL-C reduction. For statin intolerance or suboptimal response, ezetimibe and PCSK9 inhibitors provide potent, bleeding-neutral LDL-C lowering. Inclisiran and bempedoic acid broaden therapeutic options, although stroke-specific efficacy data are still pending. Lp(a)-lowering agents, including pelacarsen, olpasiran, and lepodisiran, are under active evaluation and may address residual cardiovascular risk. For triglyceride lowering, recent randomized evidence supports icosapent ethyl for reducing IS risk. In intracerebral hemorrhage (ICH), the optimal intensity and thresholds of lipid lowering remain uncertain, warranting individualized weighting of ischemic against hemorrhagic risk, particularly in patients with lobar ICH or suspected cerebral amyloid angiopathy (CAA). In such cases, hydrophilic statins, ezetimibe, or PCSK9 inhibitors may represent reasonable options. This review synthesizes current evidence and proposes a phenotype-guided, individualized framework for dyslipidemia management across stroke subtypes. Moving beyond uniform targets toward etiologic and genetically informed lipid modulation may improve post-stroke outcomes and refine individualized stroke prevention.

Introduction: Neuropathic pain (NP) in neuromyelitis optica spectrum disorder (NMOSD) represents a significant and often under-recognized complication arising from central nervous system (CNS) lesions. Unlike other demyelinating disorders, NMOSD involves a distinct immunopathogenesis primarily driven by aquaporin-4 antibodies (AQP4-IgG), leading to severe inflammatory damage. NP is typically the consequence of inflammatory damage to the spinothalamic tract or dorsal columns, resulting in both acute and chronic pain syndromes. Methods: A systematic review and meta-analysis were conducted following a comprehensive search of Medline and Scopus, identifying nine eligible studies reporting on NP in NMOSD. Results: Pooled prevalence was estimated using a random-effects metaprop meta-analysis with Freeman-Tukey transformation and REML-based heterogeneity estimation. The pooled prevalence of NP among patients with NMOSD was 56.2% (95% CI: 41.7-70.1%; I2 = 95.3%, p < 0.001). Sensitivity analysis including only AQP4-IgG+ cohorts revealed a prevalence of 63.2% (95% CI: 23.4-94.7%; I2 = 98.1%, p < 0.001). No significant difference was found between mixed and AQP4-IgG+-only populations (53.05% vs. 63.27%, p = 0.63). Meta-regression showed no significant associations between NP prevalence and age (β = 0.01, p = 0.33) or disability (β = 0.08, p = 0.18). Qualitative synthesis demonstrated an association between thoracic spinal cord lesions and NP, and also indicated that NP was often resistant and refractory to standard pharmacologic therapies. Conclusions: NP affects one in two NMOSD patients, and is associated with thoracic spinal cord lesions. In comparison with multiple sclerosis, NP in NMOSD is primarily structural and immunopathological in origin. Treatment strategies remain inadequate, emphasizing the need for early recognition and a disease-specific therapeutic approach.

BACKGROUND AND AIMS:Vascular dementia (VaD) is strongly associated with type 2 diabetes (T2DM), overweight, and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiovascular risk and exhibit neuroprotective properties, yet their effects in incident VaD remain uncertain. This study evaluated whether GLP-1 RAs have preventive potential for VaD in adults with T2DM, overweight, or obesity. METHODS:A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was conducted to estimate the risk of incident VaD among patients with T2DM or overweight/obesity treated with GLP-1 RAs versus placebo. Data were pooled using a random-effects model, with outcomes expressed as risk ratios (RRs) and 95% confidence intervals (CIs). Subgroup analysis was performed after stratification by population type (T2DM vs. overweight/obesity), and meta-regression assessed the association between RCT duration and effect size. RESULTS:Seven RCTs (six in T2DM, one in overweight/obesity) comprising 61,610 participants were included. GLP-1 RA treatment was not associated with a statistically significant difference in VaD incidence (RR: 0.50; 95% CI: 0.19-1.32; I2 = 0%). Subgroup analysis revealed no significant between-group differences (p for subgroups = 0.612), although numerically lower VaD rates were observed in the T2DM subgroup (RR: 0.38; 95% CI: 0.13-1.11). Meta-regression did not demonstrate a significant association between follow-up duration and treatment effect (β = -0.291; SE = 0.212; 95% CI: -0.843 to 0.262; p = 0.229). CONCLUSIONS:The pooled evidence did not confirm a statistically significant reduction in VaD risk with GLP-1 RA therapy. Numerically lower VaD incidence in T2DM populations warrants further investigation in adequately powered and systematically adjudicated trials.

Background and Objectives: Employment is a major determinant of quality of life in people with multiple sclerosis (pwMS). This multicenter cross-sectional study aimed to identify which commonly studied demographic, disease-related, clinical, cognitive, and psychological variables, alongside the presence of lower urinary tract symptoms (LUTS), predict employment status in pwMS. Materials and Methods: Seventy-eight pwMS were classified as either full-time employed (n = 41) or non-employed (n = 37). Participants underwent clinical and neuropsychological assessment including disability status (Expanded Disability Status Scale; EDSS), fatigue (Modified Fatigue Impact Scale; MFIS), information processing speed (Symbol Digit Modalities Test; SDMT), depressive symptoms (Hospital Anxiety and Depression Scale-Depression; HADS-D), and LUTS status (presence/absence), alongside demographic and disease-related variables (sex, age, education level, relationship status, and disease duration). Results: Hierarchical binary logistic regression indicated that higher information processing speed was associated with higher odds of employment (OR = 1.11, p = 0.008), whereas the presence of LUTS was associated with lower odds of employment (OR = 0.13, p = 0.026). Disability severity, fatigue, depressive symptoms, demographic characteristics, and disease duration did not contribute in the final model (p > 0.05). Conclusions: Information processing speed and urinary dysfunction were associated with employment status in pwMS. Within the present sample, the multivariable model including these variables showed good discrimination between employed and non-employed participants. The findings should be interpreted as exploratory, and they require further confirmation in independent cohorts before any potential application is considered.

Background/Objectives: The majority of stroke survivors undergo physical therapy rehabilitation to regain functionality and improve their overall quality of life. Given the wide range of physical therapy modalities and approaches in post stroke cardiovascular fitness rehabilitation, this systematic review and meta-analysis (SR-MA) aims to assess their efficacy as measured by peak oxygen consumption (VO2peak). Methods: Adhering to PRISMA guidelines; a detailed search of the MEDLINE PubMed; Cochrane Library; and Scopus databases was conducted. Results: Thirty-seven studies with a total of 1310 post-stroke patients were included. The aggregated mean VO2 pre-intervention was 15.30 mL/kg/min ([14.09, 16.51], I2 = 99.7%), increasing to 17.10 mL/kg/min post-intervention ([15.73, 18.46], I2 = 99.8%). The standardized mean difference in VO2 was 1.76 ([1.20, 2.31], I2 = 96.9%). Sensitivity analyses in a subset of RCTs revealed that cardiorespiratory rehabilitation demonstrates a statistically significant improvement in VO2peak levels compared to conventional physical therapy. There was a high degree of heterogeneity among included studies (potentially due to the lack of standardized protocols) while Egger’s test (β = 0.32, p = 0.72) and funnel plot inspection were indicative of moderate publication bias with small study effects. Conclusions: Based on the results of this meta-analysis, the increase in VO2peak levels post-interventions ranged from 0.28 to 3.36 mL/kg/min, depending on intervention type. The ideal time to commence aerobic training rehabilitation was found to be six months post-stroke. According to previous studies on cardiovascular diseases, VO2peak can potentially act as a predictor of (a) the efficacy of intervention and (b) the patient’s risk of stroke-recurrence and disability progression.

Lipoprotein(a) [Lp(a)] has attracted widespread interest as a potential biomarker for cerebrovascular diseases due to its genetically determined and stable plasma concentration throughout life. Lp(a) exhibits pro-atherogenic and pro-thrombotic properties that contribute to vascular pathology in both extracranial and intracranial vessels. Elevated Lp(a) levels are strongly associated with large-artery atherosclerotic stroke, while data on its role in other ischemic subtypes and hemorrhagic stroke remains limited and inconsistent. Recent advances in Lp(a)-lowering therapies, such as antisense oligonucleotides and RNA-based agents, have demonstrated significant efficacy in reducing plasma Lp(a) levels. These advances have prompted increasing research into their potential application in the prevention and treatment of cerebrovascular diseases, aiming to determine whether Lp(a) reduction may translate into a reduced risk of stroke and large-artery atherosclerosis. This narrative review summarizes the current evidence on the association between Lp(a) and stroke, focusing on its utility in patient risk stratification. It also highlights existing knowledge gaps and outlines directions for future research, particularly in understanding subtype-specific effects and evaluating the clinical benefits of Lp(a)-targeted therapies.

Background/Objectives:Myasthenia gravis (MG) comprises an autoimmune disorder marked by muscle weakness and fatigue. MG frequently coexists with other autoimmune conditions, such as diabetes mellitus, which may exacerbate the clinical burden of MG and adversely impact overall quality of life. Methods: This systematic review and meta-analysis aimed to assess the prevalence of diabetes in patients with MG. Following PRISMA guidelines, a comprehensive search was conducted in the MEDLINE PubMed, Scopus, and Google Scholar databases. Results: A total of 11 studies comprising 16,825 patients were included. The pooled prevalence of diabetes among MG patients was 15.6% (95% CI [8.4%, 24.7%]; I2 = 99%, p < 0.001). Compared to healthy controls, MG patients had a 1.24-fold increased risk of developing diabetes (95% CI [1.01–1.54], p < 0.001). Meta-regression showed no association between age and diabetes prevalence, although potential publication bias was noted (Egger’s test, p = 0.72). Conclusions: This meta-analysis reveals a higher prevalence of diabetes among MG patients, with an elevated risk compared to healthy individuals. These findings suggest that the association between MG and diabetes may be mediated by corticosteroid use, genetic factors, and reduced physical activity. The main limitations of this study are the lack of reported data regarding the type of diabetes and patients’ demographic and disease characteristics (MG classification severity and duration and type of treatment). Further studies are needed to investigate the underlying causal mechanisms and to elucidate the relationship between MG and diabetes subtypes.

Objectives:We investigated whether the acetylcholine receptor (AChR) cluster cell-based assay (CBA) is effective in detecting AChR antibodies in sera from myasthenia gravis (MG) patients with low antibody concentrations, as determined by radioimmunoprecipitation assay (RIPA). Methods:In this retrospective diagnostic cohort study, 193 RIPA-positive sera from MG patients were analyzed. Following initial assessment using the gold-standard RIPA, samples were tested with a commercially available fixed CBA (F-CBA) and an in-house live CBA (L-CBA) to detect clustered AChR antibodies. Patients were classified into three groups based on RIPA levels to evaluate the sensitivity of each CBA. A subset of the cohort was blindly retested in a second laboratory to confirm results. Results:The sensitivity of L-CBA and F-CBA in detecting 36 sera with low AChR-antibody levels (1.0-2.8 nM) was relatively high for L-CBA (83.33%, 95% CI: 71.16%, 95.51%) and low for F-CBA (45.71%, 95% CI: 29.21% to 62.22%). Both CBAs were 100% sensitive for sera with AChR-RIPA values > 3 nM. Antibodies of RIPA+/CBA- sera could be immunoadsorbed on AChR-transfected cells equally well as those from RIPA+/CBA+ sera, indicating that CBA negativity was due to low antibody concentrations. Discussion:Overall, while AChR L-CBA demonstrates good sensitivity for detecting low concentrations of AChR antibodies, F-CBA performs less reliably in such cases. Since clustered AChR-CBAs can also identify antibodies that are not detectable by RIPA, we recommend that both RIPA and CBA be used together in the routine diagnosis of MG whenever possible. When available, L-CBA should be preferred over F-CBA due to its higher sensitivity.

INTRODUCTION:Approximately 50-70% of people with multiple sclerosis (MS) experience at least one fall event during their lifetime. These events can have debilitating consequences in the quality of life of the individuals' experiencing them, as they can often result in injury, extending beyond physical harm, which may negatively impact the rehabilitation process as well as their psychological well-being. METHODS:This systematic review and meta-analysis aimed to determine the proportion of one-time and repeated falls among patients with MS within a year and investigate any potential associations with demographic and disease-specific characteristics. Adhering to PRISMA guidelines, a systematic search of the MEDLINE, PubMed, Scopus, and Google Scholar databases was conducted. RESULTS:Results from 4,342 patients were included. The pooled proportion of one fall within a year was estimated at 28.03% (95% CI [20.21, 36.57]), and for repeated falls, 31.74% (95% CI [23.73, 40.31]). Subgroup analyses revealed significant heterogeneity, while meta-regression showed no significant associations between fall prevalence and age, EDSS, or disease duration. CONCLUSION:42.5% of patients experienced a one-time fall, while 44.7% reported repeated falls. These findings, demonstrate the significant prevalence of falls among individuals with MS, underlying the need for targeted interventions to mitigate fall risk.

Alzheimer's disease (AD) is the most common cause of cognitive decline. Among the various susceptibility genes, the gene of apolipoprotein E (APOE) is probably the most important. It may be present in three allelic forms, termed ε2, ε3 and ε4, and the most common genotype is the ε3/ε3. Recently, it has been observed that subjects with the ε4/ε4 genotype may show near-full penetrance of AD biology (pathology and biomarkers), leading to the suggestion that ε4 homozygosity may represent a distinct genetic type of AD. The aim of the present study was to investigate the role of ε4 homozygosity or heterozygosity in the presence or absence of the AD biomarker profile in patients with cognitive disorders in the Greek population. A total of 274 patients were included in the study. They underwent APOE genotyping and cerebrospinal fluid (CSF) biomarker profiling. The presence of ε4 was associated with a lower age of symptom onset and decreased amyloid biomarkers (irrespective to AD or non-AD profiles), and predicted the presence of an AD profile by a positive predictive value approaching 100%. In conclusion, the ε4 allele has a significant effect on the risk and clinical parameters of cognitive impairment and AD in the Greek population, while the ε4/ε4 genotype may be highly indicative of the (co)existence of AD in cognitively impaired patients.