Publications by authors named "Lutz Froelich"

Article Synopsis
  • Dementia, particularly with severe behavioral and psychological symptoms (BPSD), greatly affects quality of life and is a main cause of death in older adults; this study looked at factors predicting mortality in these patients.
  • Over 4 years, 32.5% of 508 participants with severe BPSD died, with non-survivors generally being older, more likely male, and showing greater symptom severity and lower cognitive and functional capabilities at the start.
  • Key mortality predictors identified were male sex, older age at diagnosis, higher BPSD severity scores, lower cognitive function, worse daily living capabilities, and lower quality of life, while the use of antidepressants was linked to a reduced mortality risk.
View Article and Find Full Text PDF
Article Synopsis
  • * Concerns are raised about purely biological definitions being used in clinical settings, especially since many biomarker-positive but cognitively normal individuals may never develop symptoms, complicating diagnosis and patient understanding.
  • * The authors advocate for a combined clinical-biological definition of AD that accommodates at-risk and presymptomatic stages, emphasizing the need for caution in diagnosing AD without fully understanding the implications for patients.
View Article and Find Full Text PDF

Background: Nursing home placement (NHP) can be the final step of patients with Alzheimer's disease.

Objective: We aimed to identify NHP predictors among 508 people with dementia with a 3-year follow-up.

Methods: We analyzed data from the international observational RECage study, involving 508 people with especially Alzheimer's disease and comparing a cohort enrolled by five centers with a Special Care Unit for BPSD (behavioral and psychological symptoms of dementia) and another one enrolled by six centers lacking this facility.

View Article and Find Full Text PDF

The recent commercialisation of the first disease-modifying drugs for Alzheimer's disease emphasises the need for consensus recommendations on the rational use of biomarkers to diagnose people with suspected neurocognitive disorders in memory clinics. Most available recommendations and guidelines are either disease-centred or biomarker-centred. A European multidisciplinary taskforce consisting of 22 experts from 11 European scientific societies set out to define the first patient-centred diagnostic workflow that aims to prioritise testing for available biomarkers in individuals attending memory clinics.

View Article and Find Full Text PDF

Behavioral and psychological symptoms of dementia (BPSD) bring complexity in the clinical management of people with dementia; therefore, it is important to evaluate different models of care, such as Special Care Units (SCU-B).∥Objective:To evaluate the SCU-B effectiveness toward alleviating BPSD and improving the quality of life (QoL) of patients and their caregivers.∥Methods:ReCAGE was a multicenter, controlled, longitudinal study where 508 patients with BPSD were enrolled in two cohorts: 262 patients from centers endowed with a SCU-B, and 246 from centers without SCU-B.

View Article and Find Full Text PDF

Introduction: Clinical research with remote monitoring technologies (RMTs) has multiple advantages over standard paper-pencil tests, but also raises several ethical concerns. While several studies have addressed the issue of governance of big data in clinical research from the legal or ethical perspectives, the viewpoint of local research ethics committee (REC) members is underrepresented in the current literature. The aim of this study is therefore to find which specific ethical challenges are raised by RECs in the context of a large European study on remote monitoring in all syndromic stages of Alzheimer's disease, and what gaps remain.

View Article and Find Full Text PDF

After years of failed attempts to develop a disease-modifying therapy for Alzheimer's disease, consistent evidence in support of clinical efficacy was finally presented for a monoclonal antibody targeting the amyloid-β protofibrils. In addition to meeting the primary outcome of slowing clinical disease progression over 18 months, secondary clinical outcomes and amyloid-β lowering on PET also underpin the positive results of the trial. In this opinion piece, we highlight the key characteristics of the previous unsuccessful trials and analyse the potential reasons why those attempts to develop a treatment for early Alzheimer's disease failed.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates lecanemab, a monoclonal antibody targeting amyloid-beta, in treating early Alzheimer's disease over 18 months.
  • It involved 1,795 participants divided equally between lecanemab and placebo, focusing on cognitive impairment and amyloid levels.
  • Results showed lecanemab users had a smaller increase in cognitive impairment scores compared to the placebo group, indicating potential benefits in early Alzheimer’s treatment.
View Article and Find Full Text PDF
Article Synopsis
  • The European task force is working on a diagnostic workflow for neurocognitive disorders in older adults, focusing on how to effectively use biomarkers despite incomplete evidence for their validity.
  • They employed a Delphi consensus method, involving 22 delegates from 11 scientific societies, to gather expert opinions and establish foundational assumptions for the workflow.
  • Preliminary results suggest a structured approach emphasizing specialized clinical settings, early-stage diagnosis (MCI-mild dementia), and specific pre-assessment screenings, setting the stage for a future comprehensive guideline that adapts with new findings.
View Article and Find Full Text PDF

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis.

View Article and Find Full Text PDF

Background: Increased total tau (t-tau) in cerebrospinal fluid (CSF) is a key characteristic of Alzheimer's disease (AD) and is considered to result from neurodegeneration. T-tau levels, however, can be increased in very early disease stages, when neurodegeneration is limited, and can be normal in advanced disease stages. This suggests that t-tau levels may be driven by other mechanisms as well.

View Article and Find Full Text PDF

Background: Alzheimer's disease (AD) is a significant burden on patients and caregivers. How this burden increases as disease progresses has not been well researched.

Objective: To assess the association of caregiver burden and quality of life with Alzheimer's disease severity and disease progression in community-dwelling patients in Germany, Spain, and the UK.

View Article and Find Full Text PDF

We recently discovered three distinct pathophysiological subtypes in Alzheimer's disease (AD) using cerebrospinal fluid (CSF) proteomics: one with neuronal hyperplasticity, a second with innate immune system activation, and a third subtype with blood-brain barrier dysfunction. It remains unclear whether AD proteomic subtype profiles are a consequence of amyloid aggregation, or might exist upstream from aggregated amyloid. We studied this question in 127 older individuals with intact cognition and normal AD biomarkers in two independent cohorts (EMIF-AD MBD and ADNI).

View Article and Find Full Text PDF

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene).

View Article and Find Full Text PDF
Article Synopsis
  • - The ADAMANT trial studied AADvac1, a new vaccine targeting abnormal tau protein in Alzheimer’s disease, administered as 11 doses to patients with mild dementia over 24 months, focusing on safety, tolerability, and effectiveness.
  • - A total of 196 participants were enrolled, with AADvac1 found to be safe and well tolerated, showing some adverse events but lower serious cases compared to placebo.
  • - Although the vaccine stimulated a strong immune response, there were no significant improvements in cognitive function or clinical outcomes across the entire study group, indicating a need for more extensive research in specific subgroups to assess its efficacy.
View Article and Find Full Text PDF

Introduction: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts.

Methods: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives.

Results: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.

View Article and Find Full Text PDF

Background: The COVID-19 pandemic and governmental lockdown measures disproportionally impact older adults. This study presents the results from a psychiatric helpline for older adults in Mannheim, Germany, during the lockdown, set up to provide information and psychosocial support. We aim to elucidate the needs of older adults, their reported changes, and the psychological impact during the initial stages of the health crisis.

View Article and Find Full Text PDF

Background: There exists considerable variation in disease progression rates among patients with Alzheimer's disease (AD).

Objective: The primary objective of this observational study is to assess the progression of AD by characterizing cognitive, functional, and behavioral changes during the follow-up period between 6 and 24 months.

Methods: A longitudinal prospective study with community-dwelling patients with an established clinical diagnosis of AD of mild to moderate severity was conducted in Germany, Spain and the UK.

View Article and Find Full Text PDF

Objective: Synaptic loss plays a major role in Alzheimer's disease (AD). However so far no neurochemical marker for synaptic loss has been introduced into clinical routine. By mass spectrometry beta-synuclein was established as a candidate marker.

View Article and Find Full Text PDF

Alzheimer's disease (AD) is characterised by abnormal amyloid beta and tau processing. Previous studies reported that cerebrospinal fluid (CSF) total tau (t-tau) levels vary between patients. Here we show that CSF t-tau variability is associated with distinct impairments in neuronal plasticity mediated by gene repression factors SUZ12 and REST.

View Article and Find Full Text PDF

Synaptic degeneration is a major hallmark of Alzheimer's disease (AD) and the best pathological correlate of cognitive dysfunction. Synaptic markers are therefore a highly desired read-out for patient diagnosis and possible follow-up in clinical trials. Several synaptic markers for AD are described in cerebrospinal fluid (CSF), but studies in blood have failed so far.

View Article and Find Full Text PDF

Background: Late-life depression (LLD) is one of the most prevalent mental disorders in old age. It is associated with various adverse outcomes and frequent use of health care services thereby remaining a serious public health concern. Compared with depression in early adulthood, most treatment options of LLD are less effective.

View Article and Find Full Text PDF