Background and ObjectivesFrontotemporal lobar degeneration (FTLD) can present as a behavioral or language variant (bvFTLD or a primary progressive aphasia [PPA], or as a syndrome with parkinsonism, such as corticobasal syndrome [CBS] or progressive supranuclear palsy [PSP]). The incidence of FTLD varies in epidemiologic studies, reaching 3 per 100,000 person-years. Only few data exist regarding survival times. We evaluated incidence and survival rates in a population-based registry with high coverage in Southern Germany.MethodsThe epidemiologic ALS-FTLD registry Swabia covers a population of 8.4 million inhabitants in south-west Germany. Raw and age-standardized incidence rates, as well as incidence rate ratios (IRR) with 95% CIs were calculated. Median survival time was estimated for different FTLD variants using the Kaplan-Meier method.ResultsBetween 2015 and 2022, 515 patients with FTLD (mean age at diagnosis 68.0 +/- 9.5 years, 59.8% men) were registered. The median diagnostic delay was 24.8 months. The most common variant was bvFTLD (n = 185, 35.9%; 66.5% men), followed by PPA (n = 147, 28.5%; 51.0% men), PSP (n = 133, 25.8%; 62.9% men), and CBS (n = 22, 4.3%; 50% men). The overall FTLD incidence was 0.77 (95% CI 0.71-0.84), and the age-standardized incidence was 0.76 (95% CI 0.69-0.82) per 100.000 person-years. The age-standardized incidence was higher in men than in women, with an IRR of 1.73 (95% CI 1.44-2.00). In men, incidence increased from the age 50 years, primarily due to bvFTD, whereas in women this rise was primarily due to PSP. The median survival (N = 392) from diagnosis was 53.6 months (95% CI 50.9-62.0) overall, 73.1 months (95% CI 63.6-82.8) for patients with PPA, 42.8 months (95% CI 35.1-64.3) for patients with bvFTD, and 49.5 months (95% CI 39.2-53.7) for patients with PPS/CBS.DiscussionWe observed a raw incidence rate of 0.77, thus considerably lower than in most previous reports. Incidence was substantially higher in men than in women. The prognosis from the time of diagnosis depended highly on the specific FTLD subtype. Our data are based on the large sample size and high capture rate of a central European population-based registry.

BACKGROUND AND OBJECTIVES:Frontotemporal lobar degeneration (FTLD) can present as a behavioral or language variant (bvFTLD or a primary progressive aphasia [PPA], or as a syndrome with parkinsonism, such as corticobasal syndrome [CBS] or progressive supranuclear palsy [PSP]). The incidence of FTLD varies in epidemiologic studies, reaching 3 per 100,000 person-years. Only few data exist regarding survival times. We evaluated incidence and survival rates in a population-based registry with high coverage in Southern Germany. METHODS:The epidemiologic ALS-FTLD registry Swabia covers a population of 8.4 million inhabitants in south-west Germany. Raw and age-standardized incidence rates, as well as incidence rate ratios (IRR) with 95% CIs were calculated. Median survival time was estimated for different FTLD variants using the Kaplan-Meier method. RESULTS:Between 2015 and 2022, 515 patients with FTLD (mean age at diagnosis 68.0 ± 9.5 years, 59.8% men) were registered. The median diagnostic delay was 24.8 months. The most common variant was bvFTLD (n = 185, 35.9%; 66.5% men), followed by PPA (n = 147, 28.5%; 51.0% men), PSP (n = 133, 25.8%; 62.9% men), and CBS (n = 22, 4.3%; 50% men). The overall FTLD incidence was 0.77 (95% CI 0.71-0.84), and the age-standardized incidence was 0.76 (95% CI 0.69-0.82) per 100.000 person-years. The age-standardized incidence was higher in men than in women, with an IRR of 1.73 (95% CI 1.44-2.00). In men, incidence increased from the age 50 years, primarily due to bvFTD, whereas in women this rise was primarily due to PSP. The median survival (N = 392) from diagnosis was 53.6 months (95% CI 50.9-62.0) overall, 73.1 months (95% CI 63.6-82.8) for patients with PPA, 42.8 months (95% CI 35.1-64.3) for patients with bvFTD, and 49.5 months (95% CI 39.2-53.7) for patients with PPS/CBS. DISCUSSION:We observed a raw incidence rate of 0.77, thus considerably lower than in most previous reports. Incidence was substantially higher in men than in women. The prognosis from the time of diagnosis depended highly on the specific FTLD subtype. Our data are based on the large sample size and high capture rate of a central European population-based registry.

Abstract Background Fatigue and cognitive impairment are common in multiple sclerosis (MS) affecting up to 95% and 65% of the patients, respectively. Only little is known about the interplay of different volumetric magnetic resonance imaging (MRI) parameters, the serum biomarkers neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP), cognition, and fatigue in MS patients without signs of progression independent of relapse activity (PIRA; i.e. clinically stable). This study aimed to evaluate whether volumetric MRI and serum NfL and GFAP are associated with cognitive impairment and fatigue in clinically stable relapsing-remitting multiple sclerosis (RRMS) and to examine whether the Expanded Disability Status Scale (EDSS) has an added value. Methods A retrospective mono-centric cohort of 54 clinically stable (no disability worsening/relapse-free) RRMS patients underwent comprehensive clinical assessment with the EDSS, Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS-M), Fatigue Scale for Motor and Cognitive Functions (FSMC), in addition to established biomarkers of MS pathology, including sNfL, sGFAP, and magnetic resonance imaging (MRI: thalamic/hippocampal/whole brain parenchymal volumes/annualized brain volume loss (BVL/year)). Associations were examined using regressions, correlations, and group comparisons. Results Thalamic and hippocampal volumes were significantly lower in cognitively impaired than non-impaired patients (both p<.001), while sNfL and sGFAP showed no group differences (p>.35; p>.09). Fatigue was not associated with MRI or serum markers (p>.09). BICAMS-M correlated with EDSS (r=–.56; p<.001) to a similar extent as with thalamic or hippocampal volumes (r=.55; p<.001). BVL/year was highly associated with cognitive impairment, explaining 63.2% (BICAMS-M) of the variance (p<.001). Conclusion In our clinically stable, small RRMS cohort, BVL/year, thalamic and hippocampal volumes are associated with cognition in contrast to sNfL and sGFAP. EDSS as a global disability score correlates with cognition but adds little beyond MRI. These results require further validation using a prospective design and broader cohort.

Approximately 7% of adults develop Post-COVID-19 syndrome (PCS). Cognitive impairment is common, but its profile in PCS is not well defined and requires clearer differentiation from general (post-)illness effects. The aim of this study was to identify distinct cognitive profiles in PCS and to characterize them with respect to broader psychological factors such as fatigue, depression, anxiety, and personality. To this end, we assessed cognition, fatigue, depression, anxiety, and personality traits in PCS patients, convalescents (CV), healthy controls (HC), and post-viral syndrome patients (PV) of different etiology. Cognitive performance was assessed with an extensive protocol covering multiple cognitive domains, including verbal and nonverbal short-term memory, verbal and nonverbal working memory, verbal and nonverbal episodic memory, visuoconstruction, attentional functions, and executive functions, alongside patient-reported measures of fatigue, depression, anxiety, and personality, as well as self-reported information on lifetime psychiatric diagnoses. Group comparisons and discriminant analysis (p = .065) identified the tests that best differentiate the groups, while exploratory cluster analysis allowed for data-driven group assignment. In this study, N = 54 PCS, N = 42 HC, N = 25 CV, and N = 12 PV were included. Patients with PCS show low mean scores and cluster into two subgroups: 7.5% with severe objective cognitive impairments (PCSSCI) and 92.5% with cognitive performance comparable to CV, HC, and PV (Mixed(non-SCI)). The PCSSCI subgroup showed pronounced objective impairments, particularly in attentional, memory, and executive domains. Across the entire PCS sample, objective cognitive impairments were not predicted by fatigue severity or affective state (depression or anxiety), although lifetime psychiatric disorders and cognitive fatigue were significantly more prevalent in PCSSCI. Among patients with PCS, a distinct subgroup of individuals presents with severe cognitive deficits, significant cognitive fatigue, and an increased lifetime vulnerability for psychiatric disorders, highlighting the need for targeted diagnostic assessments and personalized (psycho-)therapeutic interventions.

Background/Objectives: Cognitive impairment is one of the most common and debilitating clinical features of Multiple Sclerosis (MS). Neuropsychological assessment, however, is time-consuming and requires personal resources, so, due to limited resources in daily clinical practice, information on cognitive profiles is often lacking, despite its high prognostic relevance. Time-saving and effective tools are required to bridge this gap. This study evaluates the sensitivity and specificity of a revised version of TRACK-MS (TRACK-MS-R), a recently published screening tool to identify cognitive impairment in MS in a fast and reliable way, offering a balance between efficiency and diagnostic yield for the individual patient. Methods: In this prospective cross-sectional study, 102 MS patients and 94 age-, sex-, and education-matched healthy controls (HC) completed an extensive neuropsychological assessment, including TRACK-MS-R, to test for cognitive processing speed (Symbol Digit Modalities Test, SDMT) and verbal fluency (Regensburger Word Fluency Test, RWT). Sensitivity of TRACK-MS-R was assessed by using the BICAMS-M battery as a reference, and specificity was determined by comparing MS patients to HC. Results: TRACK-MS-R demonstrated high sensitivity (97.44%) when compared to the gold standard as represented by BICAMS-M for early and accurately detecting cognitive impairment in MS patients. Additionally, as a potential cognitive marker, TRACK-MS-R showed a specificity of 82.98% in distinguishing MS patients from healthy controls. Conclusions: TRACK-MS-R proves to be a highly sensitive and time-efficient screening tool for detecting cognitive impairment in patients with MS, while demonstrating good specificity compared to HC. Whereas high sensitivity is a prerequisite for a valid screening tool, its relatively modest specificity compared to BICAMS-M (62.9%) calls for caution in interpreting standalone results but instead indicates more extensive neuropsychological testing. Its briefness and diagnostic accuracy support its implementation in routine clinical practice, particularly in time-constrained settings.

Multiple sclerosis (MS) subtypes—relapsing–remitting (RRMS), secondary-progressive (SPMS), and primary-progressive (PPMS) – have been associated with distinct cognitive impairment profiles, with progressive subtypes, in contrast to RRMS, showing additional deficits in more widespread domains. Research has largely focused on RRMS, leaving SPMS and PPMS underexplored due to their lower prevalence and limited therapeutic targeting. Data on the interplay between cognitive impairment, mood, and fatigue over time are also scarce. This study examined cognition, fatigue, and psychopathology over a period of one year to identify subtype-specific impairments and progression trajectories. Sixty-six MS patients (22 each with RRMS, SPMS, and PPMS) and 22 healthy controls (HC) were assessed using neuropsychological tests for attention, memory, processing speed, working memory, fluency and visuospatial functions. Patient-reported outcomes for depression, anxiety, and fatigue were also collected. Analyses included correlations, within-group comparisons (paired t-tests), and between-group comparisons (ANOVAs/ANCOVAs). Progressive MS subtypes exhibited more severe cognitive impairments, fatigue, and mood disturbances than RRMS. Over one year, treated RRMS patients improved in various cognitive domains, while PPMS patients showed gains only in visuospatial abilities. On the other hand, SPMS patients exhibited no significant changes, suggesting more pronounced cognitive deficits. Cognitive impairments differed significantly across MS subtypes. While RRMS patients improved over one year and PPMS patients showed selective gains in one domain, SPMS showed no significant changes, indicating reduced cognitive reserve. These between-group differences suggest different cognitive trajectories. The findings underscore the need for tailored, holistic interventions for different MS subtypes.

Background/Objectives: Multiple sclerosis (MS) is a complex neurological disease that is associated with a broad spectrum of physical and psychological symptoms. Psychosocial adjustment (PSA) refers to the ability to cope with these challenges, which influence quality of life (QoL) and depressiveness in ways not yet fully understood. This study explores the relationship of PSA and disease-specific symptoms in MS, including fatigue, a prominent MS symptom. Additionally, PSA was compared to Amyotrophic Lateral Sclerosis (ALS) to disentangle the impact of disease trajectory on PSA. Methods: We interviewed 77 MS patients using patient-reported outcome measures on QoL and depression and compared them to 30 ALS patients. Confirmatory factor analysis and regression analysis were used to identify PSA indicators and predictors in MS, while t-tests assessed PSA differences across diseases. Results: Key PSA indicators in MS included physical (PQoL), mental (MQoL), and subjective (SQoL) quality of life, as well as depressiveness, with cognitive and motor fatigue emerging as significant predictors. MS patients had higher PQoL and SQoL and lower levels of depression compared to ALS patients, while both groups were comparable with regard to MQoL. Conclusions: PSA in MS is supported by high QoL and low depression levels, with fatigue being a significant predictor. Despite different disease trajectories, patients with MS and ALS showed comparable MQoL, indicating that both diseases similarly impact mental QoL, reflecting a partial overlap in psychosocial adjustment. Overall, psychosocial adjustment was more favorable in MS, likely due to its slower disease progression compared to ALS.

OBJECTIVE:The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) is an established cognitive screening instrument for patients with amyotrophic lateral sclerosis (ALS). Different from tools like the Mini-Mental State Examination (MMSE), it is adjusted for motor impairment, yet, the latter remains one of the most widely used screening instruments, also in ALS studies. Thus, it is of utmost importance to relate outcome scores of both instruments to allow for comparison in ALS patients. This study reports on the performance of ALS patients in both tests with regard to incidence and degree of cognitive impairment, and the correspondence of both, ECAS and MMSE scores.METHODS:We examined N = 84 ALS patients with the German versions of the ECAS and the MMSE. Performance in both tests regarding incidence and degree of cognitive impairment, and correspondence of frequency of cognitive impairment according to both tests was examined. The relationship between ECAS and MMSE scores was modelled with a non-linear regression model.RESULTS:All ALS patients were able to complete the ECAS, 89.3% (N = 75) were capable to complete the MMSE. Prevalence of cognitive impairment was in both tests 22.7%, however agreement was only 52.9%. Despite, regression analyses yielded a strong positive relationship (adjusted R2 = .68) between the ECAS total score and the MMSE total score. Both tests were able to identify all patients with dementia.CONCLUSION:These results suggest that the MMSE is not ideal for cognitive screening in early-stage ALS patients. However, a rough translation of MMSE scores in ECAS scores is possible to estimate the cognitive performance level of patients, with the ECAS being more discriminative in the lower range of cognitive dysfunction (ECAS score: 80-136), for which the MMSE does not define cognitive impairment (corresponding MMSE score: 27-30).

In Germany, around 1.8 million people currently suffer from dementia and the numbers are increasing. The main cause of dementia is Alzheimer's disease. This is classically manifested in the form of an amnestic syndrome but also encompasses various atypical variants, especially in younger patients and in the clinical routine are not always easy to recognize. These are described in this narrative review with case studies. Posterior cortical atrophy (PCA) presents with visual disorders, in the logopenic variants of primary progressive aphasia (lvPPA) impaired word retrieval is the main symptom, in the frontal variant of Alzheimer's disease behavioral disorders are prominent and in corticobasal syndrome (CBS) an akinetic rigid Parkinson's syndrome with alien limb phenomenon. As the clinical presentation of these atypical variants shows an overlap with other dementia disorders, the differential diagnosis is often challenging. In this context amyloid biomarkers can provide valuable services.

OBJECTIVES:Up to 50% of patients with amyotrophic lateral sclerosis (ALS) present with cognitive problems and behavioral dysfunctions including recognition of human faces presenting different emotions. We investigated whether impaired processing of emotional faces is associated with abnormal scan paths during visual exploration.METHODS:Cognitively unimpaired patients with ALS (n = 45) and matched healthy controls (n = 37) underwent neuropsychological assessment and video-based eye tracking. Eye movements were recorded while participants visually explored faces expressing different emotions (neutral, disgusted, happy, fearful, and sad) and houses mimicking faces.RESULTS:Compared with controls, patients with ALS fixated significantly longer to regions which are not relevant for emotional information when faces expressed fear (p = 0.007) and disgust (p = 0.006), whereas the eyes received less attention in faces expressing disgust (p = 0.041). Fixation duration in any area of interest was not significantly associated with the cognitive state or clinical symptoms of disease severity.DISCUSSION:In cognitively unimpaired patients with ALS, altered gaze patterns while visually exploring faces expressing different emotions might derive from impaired top-down attentional control with possible involvement of subliminal frontotemporal areas. This may account for indistinctness in emotion recognition reported in previous studies because nonsalient features retrieve more attention compared with salient areas. Current findings may indicate distinct emotion processing dysfunction of ALS pathology, which may be different from, for example, executive dysfunction.

In Germany, around 1.8 million people currently suffer fromdementia and the numbers are increasing. The main cause of dementia is Alzheimer's disease. This is classically manifested in the form of an amnestic syndrome but also encompasses various atypical variants, especially in younger patients and in the clinical routine are not always easy to recognize. These are described in this narrative review with case studies. Posterior cortical atrophy (PCA) presents with visual disorders, in the logopenic variants of primary progressive aphasia (lvPPA) impaired word retrieval is the main symptom, in the frontal variant of Alzheimer's disease behavioral disorders are prominent and in corticobasal syndrome (CBS) an akinetic rigid Parkinson's syndrome with alien limb phenomenon. As the clinical presentation of these atypical variants shows an overlap with other dementia disorders, the differential diagnosis is often challenging. In this context amyloid biomarkers can provide valuable services.

Objective: Age and years of education are strong predictors of cognitive performance in several versions of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) and cutoffs for the Swedish and Polish versions are not established yet. Here we evaluated the performance of healthy subjects on the national versions of the Swedish and Polish ECAS and compared cognitive performance on three European translations of the ECAS. Methods: The ECAS performances of healthy subjects from Sweden (n = 111), Poland (n = 124) and Germany (n = 86) were compared. Based on the test results on the national versions of ECAS, age- and education-adjusted cutoffs were compared for the German, Swedish and Polish versions, respectively. Results: Age and years of education correlated with performance in the ECAS. Swedish subjects under the age of 60 years and Swedish subjects with low education level scored significantly higher in memory than the respective German and Polish subgroups. German and Polish subjects over 60 years of age performed significantly better in language than the respective Swedish subgroup. The Polish cohort in total had lower executive scores compared to the Swedish cohort, and lower than the German subjects in the higher education subgroup. Conclusions: The results highlight the importance of establishing age- and education-adjusted ECAS cutoffs not only in general, but also for seemingly similar populations of different origins. The results should be taken into account when comparing cognition data across patient populations including in drug trials where an ECAS test result is being used as an inclusion criterium or outcome measure.

Demenzerkrankungen werden immer häufiger. In Deutschland sind aktuell rund 1,8 Mio. Menschen an Demenz erkrankt. Die Hauptursache von Demenzerkrankungen ist die Alzheimer-Erkrankung. Diese äußert sich klassischerweise in Form eines amnestischen Syndroms, umfasst aber auch verschiedene atypische Varianten, die vor allem jüngere Patienten betreffen und im klinischen Alltag nicht immer einfach zu erkennen sind. Diese werden im folgenden narrativen Review, teils mit Kasuistiken unterlegt, beschrieben. Die posteriore kortikale Atrophie (PCA) präsentiert sich mit visuellen Störungen, bei der logopenischen Variante der primär progredienten Aphasie (lvPPA) stehen Wortfindungsstörungen im Vordergrund, bei der frontalen Variante der Alzheimer-Erkrankung Verhaltensstörungen und beim kortikobasalen Syndrom (CBS) ein akinetisch-rigides Parkinson-Syndrom mit Apraxie und „Alien-limb-Phänomen“. Da das klinische Bild dieser atypischen Varianten eine Überlappung mit anderen Demenzerkrankungen zeigt, ist die Differenzialdiagnose oft herausfordernd. Amyloid-Biomarker können hier wertvolle Dienste leisten.

Background: During the course of amyotrophic lateral sclerosis (ALS), patients and their families are faced with existential decisions concerning life-prolonging and -shortening measures. Correct anticipation of patient's well-being and preferences is a prerequisite for patient-centered surrogate decision making. Methods: In Germany (N = 84), Poland (N = 77) and Sweden (N = 73) patient-caregiver dyads were interviewed. Standardized questionnaires on well-being (ADI-12 for depressiveness; ACSA for global quality of life) and wish for hastened death (SAHD) were used in ALS patients. Additionally, caregivers were asked to fill out the same questionnaires by anticipating patients' perspective (surrogate perspective). Results: Caregivers significantly underestimated patients' well-being in Germany and Poland. For Swedish caregivers, there were just as many who underestimated and overestimated well-being. The same was true for wish for hastened death in all three countries. For Swedish and Polish patients, caregivers' estimation of well-being was not even associated with patients' responses and the same was true for estimation of wish for hastened death in all three countries. Older caregivers and those with the most frequent encounter with the patient were the closest in their rating of well-being and wish for hastened death to the patients' actual state, while caregivers with chronic disease him/herself were more likely to underestimate patient's well-being. Discussion: Despite distinct cultural differences, there was a clear discrepancy between patients' and caregivers' perspective on patients' well-being and preferences towards life in all three countries. This possible bias in caregivers' judgment needs to be taken into account in surrogate decision making.

Tracking cognition in patients with multiple sclerosis (MS) is important for detection of disease progression but it is often not performed in routine settings due to time constraints. This exploratory cohort study aims to develop a very brief repeatable tracking tool with comparable test quality criteria to the current gold standard, the Brief International Cognitive Assessment for MS (BICAMS). The study included 88 participants (22 healthy controls, 66 MS patients) who were examined at baseline and at one-year follow-up. As a validity criterion for the six administered cognitive tests, we assessed the difference between MS patients and HC, and the correlation with MS-related disability. Combining the two tests with the highest validity—the Controlled Oral Word Association Test and Symbol Digit Modalities Test—yielded an administration time of 5 min. Comparing this new TRACK-MS test battery with the 15 min BICAMS indicated that TRACK-MS showed larger differences between MS patients and healthy controls, a higher correlation with MS-related disability, smaller practice effects, and a good test–retest reliability. We provide evidence that TRACK-MS, although faster to administer, showed at least comparable quality criteria as the BICAMS. As the study was exploratory, replication of these results is necessary.