Gerhard Ransmayr

Summary: Background: Disease-modifying therapies with amyloid-antibodies will soon be available for patients with early Alzheimer’s disease, which necessitates diagnostic and therapeutic resources in hospital and outpatient settings. Methods: The Austrian Alzheimer Society developed an online questionnaire to survey Austrian hospital-based departments of neurology and psychiatry regarding resources for amyloid-antibody therapies. Results: Between May and October 2023, 30 out of 41 neurology (73%) and 12 out of 33 psychiatry departments (36%) responded. The number of first examinations per year and center ranges between 0 in centers accepting only secondary referrals and 500, median 100. Of the patients 30% (median; range 0–80%) achieve a mini-mental state examination sum score ≥ 22 constituting an early disease stage. First visits comprise medical history, clinical examination, routine blood sampling and neurocognitive screening in 90–100% of patients, magnetic resonance imaging in 90% (median; range 10–100%), amyloid-PET in 5% (0–70%), cerebrospinal fluid analysis (Aß42, Aß40, tau, phospho-tau) in 25% (0–90%) and Apo‑E testing in 2.5% (0–100%). To assess the amyloid status 18 centers (44%) prefer amyloid-PET to lumbar puncture, 20 (49%) vice versa and 15 centers intend to offer amyloid-antibody therapy. Summary: Differences between centers and federal states were observed regarding hospital-based resources for amyloid-antibody therapies. A substantial need exists for early dementia diagnosis, medical, neuropsychological, nursing and administrative resources, adequate space, access to amyloid-PET and MRI. All centers highlighted the need for structured patient pathways and multidisciplinary care networks, including neurologists, psychiatrists, radiologists, neuropsychologists operating in clinical practice, rehabilitation and dementia care settings.

Language impairments, hallmarks of speech/language variant progressive supranuclear palsy, also occur in Richardson’s syndrome (PSP-RS). Impaired communication may interfere with daily activities. Therefore, assessment of language functions is crucial. It is uncertain whether the Aachen Aphasia Test (AAT) is practicable in PSP-RS, behavioral variant frontotemporal dementia (bvFTD) and Alzheimer’s dementia (AD) and language deficits differ in these disorders. 28 PSP-RS, 24 AD, and 24 bvFTD patients were investigated using the AAT and the CERAD-Plus battery. 16–25% of all patients failed in AAT subtests for various reasons. The AAT syndrome algorithm diagnosed amnestic aphasia in 5 (23%) PSP-RS, 7 (36%) bvFTD and 6 (30%) AD patients, Broca aphasia in 1 PSP-RS and 1 bvFTD patient, Wernicke aphasia in 1 bvFTD and 3 (15%) AD patients. However, aphasic symptoms resembled non-fluent primary progressive aphasia in 14 PSP-RS patients. In up to 46% of PSP-RS patients, 61% of bvFTD and 64% of AD patients significant impairments were found in the AAT subtests spontaneous speech, written language, naming, language repetition, language comprehension and the Token subtest. The CERAD-Plus subtest semantic fluency revealed significant impairment in 81% of PSP-RS, 61% of bvFTD, 44% of AD patients, the phonemic fluency subtest in 31, 40 and 31%, respectively. In contrast to bvFTD and AD, severity of language impairment did not correlate with cognitive decline in PSP-RS. In summary, the patterns of aphasia differ between the diagnoses. Local frontal language networks might be impaired in PSP-RS, whereas in AD and bvFTD, more widespread neuropathology might underly language impairment.

Background and Objectives: The neurofilament light chain (NfL) is a biomarker for neuro-axonal injury in various acute and chronic neurological disorders, including Alzheimer’s disease (AD). We here investigated the cross-sectional and longitudinal associations between baseline serum NfL (sNfL) levels and cognitive, behavioural as well as MR volumetric findings in the Prospective Dementia Registry Austria (PRODEM-Austria). Materials and Methods: All participants were clinically diagnosed with AD according to NINCDS-ADRDA criteria and underwent a detailed clinical assessment, cognitive testing (including the Mini Mental State Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD)), the neuropsychiatric inventory (NPI) and laboratory evaluation. A total of 237 patients were included in the study. Follow-up examinations were done at 6 months, 1 year and 2 years with 93.3% of patients undergoing at least one follow-up. We quantified sNfL by a single molecule array (Simoa). In a subgroup of 125 subjects, brain imaging data (1.5 or 3T MRI, with 1 mm isotropic resolution) were available. Brain volumetry was assessed using the FreeSurfer image analysis suite (v6.0). Results: Higher sNfL concentrations were associated with worse performance in cognitive tests at baseline, including CERAD (B = −10.084, SE = 2.999, p < 0.001) and MMSE (B = −3.014, SE = 1.293, p = 0.021). The sNfL levels also correlated with the presence of neuropsychiatric symptoms (NPI total score: r = 0.138, p = 0.041) and with smaller volumes of the temporal lobe (B = −0.012, SE = 0.003, p = 0.001), the hippocampus (B = −0.001, SE = 0.000201, p = 0.013), the entorhinal (B = −0.000308, SE = 0.000124, p = 0.014), and the parahippocampal cortex (B = −0.000316, SE = 0.000113, p = 0.006). The sNfL values predicted more pronounced cognitive decline over the mean follow-up period of 22 months, but there were no significant associations with respect to change in neuropsychiatric symptoms and brain volumetric measures. Conclusions: the sNfL levels relate to cognitive, behavioural, and imaging hallmarks of AD and predicts short term cognitive decline.

MRI studies have consistently identified atrophy patterns in Alzheimer’s disease (AD) through a whole-brain voxel-based analysis, but efforts to investigate morphometric profiles using anatomically standardized and automated whole-brain ROI analyses, performed at the individual subject space, are still lacking. In this study we aimed (i) to utilize atlas-derived measurements of cortical thickness and subcortical volumes, including of the hippocampal subfields, to identify atrophy patterns in early-stage AD, and (ii) to compare cognitive profiles at baseline and during a one-year follow-up of those previously identified morphometric AD subtypes to predict disease progression. Through a prospectively recruited multi-center study, conducted at four Austrian sites, 120 patients were included with probable AD, a disease onset beyond 60 years and a clinical dementia rating of ≤1. Morphometric measures of T1-weighted images were obtained using FreeSurfer. A principal component and subsequent cluster analysis identified four morphometric subtypes, including (i) hippocampal predominant (30.8%), (ii) hippocampal-temporo-parietal (29.2%), (iii) parieto-temporal (hippocampal sparing, 20.8%) and (iv) hippocampal-temporal (19.2%) atrophy patterns that were associated with phenotypes differing predominately in the presentation and progression of verbal memory and visuospatial impairments. These morphologically distinct subtypes are based on standardized brain regions, which are anatomically defined and freely accessible so as to validate its diagnostic accuracy and enhance the prediction of disease progression.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) progress relentlessly and lead to a need for care. Caregiving is often burdensome. Little is known about the course of caregiver burden (CB) in PSP and CBS patients. Longitudinal analysis of CB in family members caring for PSP and CBS patients. Single-center longitudinal pilot study in 68 newly diagnosed patients with probable PSP and CBS (52 Richardson’s syndrome; 1 progressive gait freezing of PSP; 15 CBS). Demographic, educational, occupational parameters, family status, motor functions (UPDRSIII, Hoehn and Yahr Score, Tinetti) and neuropsychological performance (CERAD Plus, Frontal Assessment Battery) were assessed, as well as behavioral and neuropsychiatric impairments (Frontal Behavioral Inventory, Neuropsychiatric Inventory), activities of daily living (ADL) and caregiver burden using the Caregiver Strain Index (CSI), in most patients also the Zarit Burden Interview (ZBI). Patients were followed up every 6 months for up to 2 years. Caregivers reported mild to moderate CB at baseline, which increased by 25–30% in 2 years and was significantly greater in PSP than in CBS. Risk for mental health problems increased over time, especially in female caregivers (depression). Important patient-related factors were apathy, aspontaneity, depression, irritability, disorganization, poor judgment, impairment of language, impairments in ADL, a high educational level of the patient and close family relationship. Behavioral symptoms and impaired ADL are the main patient-related factors of CB in PSP and CBS. CB can be severe and needs to be assessed repeatedly from the time of diagnosis to provide comprehensive support.

Studies on caregiver burden in patients with frontotemporal lobar degeneration are rare, differ methodologically and show variable results. Single center longitudinal pilot study on caregiver burden and potential risk factors in patients with behavioural variant frontotemporal dementia (bvFTD) and semantic (svPPA) and non-fluent variants (nfvPPA) primary progressive aphasia. Forty-six bvFTD, nine svPPA, and six nfvPPA patients and caring relatives were analysed for up to 2 years using the Mini-Mental State Examination as global measure for cognitive performance, Frontal Assessment Battery (frontal lobe functions), Frontal Behavioural Inventory (personality and behaviour), Neuropsychiatric Inventory (dementia-related neuropsychiatric symptoms), Barthel Index and Lawton IADL Scale (basic and instrumental activities of daily living), the Caregiver Strain Index (CSI), and in most participants also the Zarit Burden Interview (ZBI). CSI baseline sum scores were highest in bvFTD (mean ± SD 5.5 ± 3.4, median 5, IQR 6), intermediate in svPPA (2.9 ± 2.3; 3; 3.5) and low in nfvPPA (1.6 ± 2.1; 1; 2). Similar differences of caregiver burden were found using the ZBI. During follow-up, CSI and ZBI sum scores deteriorated in svPPA, not in bvFTD and nfvPPA, and correlated significantly with personality and behaviour, neuropsychiatric symptoms, caregiver age, and instrumental, but not basic activities of daily living, Mini-Mental State Examination scores or frontal lobe functions. This study reveals differences in caregiver burden in variants of frontotemporal lobar degeneration. Caregivers should be systematically asked for caregiver burden from the time of the diagnosis to provide comprehensive support in time.

Summary: A substantial number of neurological diseases lead to chronic impairment of activities of daily living (ADL) and physical or mental dependence. In Austria, homecare is provided mostly by female family members. Moreover, mainly female personnel, in the majority from southern and eastern European countries, contributes to care. Dependence and need for care vary between neurological diagnoses and accompanying diseases. Caregiver burden (CB) depends on patient- and caregiver-related and external factors, such as integrity of a family network, spatial resources, and socioeconomic factors. Depending on the neurological diagnosis, disease severity, and behavioral impairment and psychiatric symptoms, caregivers (CG) are at a significant risk of mental and somatic health problems because of limitations in personal needs, occupational and social obligations, financial burden, and restricted family life and leisure. Subjective and objective CB needs to be assessed in time and support should be provided on an individual basis. Recently, COVID-19 has caused additional multifactorial distress to dependent patients and informal and professional CG.

Zusammenfassung: Patientinnen und Patienten (Pat.) mit Parkinson-Krankheit bedürfen mit zunehmender Krankheitsdauer und Schweregrad persönlicher Betreuung, die meist von weiblichen Angehörigen gewährleistet wird. Die Belastungen für pflegende Angehörige resultieren einerseits aus den motorischen Beeinträchtigungen der Pat., andererseits von neurokognitiven und neuropsychiatrischen Symptomen sowie Verhaltensstörungen, Störungen des autonomen Nervensystems, der Miktion, des Schlafes und der Selbstständigkeit. Gesundheitliche Probleme der Betreuungsperson, u. a. Depression und Angst, emotionale Probleme mit dem Pflegling, Beeinträchtigung des Schlafs, sowie Einschränkungen in persönlichen Anliegen, Beruf, Familie, Freizeitgestaltung, sozialen Aktivitäten, finanzielle Einbußen und mangelhafte soziale Unterstützung stellen weitere Belastungsfaktoren dar. Personen mit dem Risiko einer erheblichen Betreuungsbelastung sind frühzeitig zu identifizieren, um ihnen Informationen über die Krankheit und Unterstützungsmöglichkeiten sowie entsprechende personelle, psychologische und finanzielle Unterstützung zukommen zu lassen.