Feasibility and potential diagnostic value of [F]PI-2620 PET in patients with down syndrome and Alzheimer's disease: a case series.

Purpose Of The Report: Adults with Down Syndrome (DS) have a substantially increased risk for Alzheimer's disease (AD) due to the triplicated amyloid-precursor-protein gene on chromosome 21, resulting in amyloid and tau accumulation. However, tau PET assessments are not sufficiently implemented in DS-AD research or clinical work-up, and second-generation tau tracers such as [F]PI-2620 have not been thoroughly characterized in adults with DS. We aim at illustrating feasibility and potential diagnostic value of tau PET imaging with [F]PI-2620 for the diagnosis of DS-AD.

Measurement properties of the German version of the Cambridge examination for mental disorders of older people with Down syndrome and others with intellectual disabilities (CAMDEX-DS).

Background: The CAMDEX-DS is an instrument to diagnose Alzheimer's disease (AD) in Down syndrome consisting of an informant interview and a cognitive test battery (CAMCOG-DS). Measurement properties of the German CAMDEX-DS were investigated.

Method: Fifty-five adults with Down syndrome (19-58 years) participated in this observational study.

Frequency and Longitudinal Course of Behavioral and Neuropsychiatric Symptoms in Participants With Genetic Frontotemporal Dementia.

Background And Objectives: Behavioral and neuropsychiatric symptoms are frequent in patients with genetic frontotemporal dementia (FTD). We aimed to describe behavioral and neuropsychiatric phenotypes in genetic FTD, quantify their temporal association, and investigate their regional association with brain atrophy.

Methods: We analyzed data of pathogenic variant carriers in the chromosome 9 open reading frame 72 (), progranulin (), or microtubule-associated protein tau () gene from the Genetic Frontotemporal dementia Initiative cohort study that enrolls both symptomatic pathogenic variant carriers and first-degree relatives of known carriers.

Validation of a German version of the dementia screening questionnaire for individuals with intellectual disabilities (DSQIID-G) in Down's syndrome.

Background: People with Down's syndrome (DS) are at high risk of developing Alzheimer dementia (DS-AD) due to a triplication of the amyloid precursor protein gene. While several tools to diagnose and screen for DS-AD, such as the dementia screening questionnaire for individuals with intellectual disabilities (DSQIID), are available in English, validated German versions of such instruments are scarce.

Methods: A German version of the DSQIID questionnaire (DSQIID-G) was completed by caregivers before attending our specialist outpatient department for DS-AD.

Symptomatology in 4-repeat tauopathies is associated with data-driven topology of [F]-PI-2620 tau-PET signal.

In recent years in vivo visualization of tau deposits has become possible with various PET radiotracers. The tau tracer [F]PI-2620 proved high affinity both to 3-repeat/4-repeat tau in Alzheimer's disease as well as to 4-repeat tau in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). However, to be clinically relevant, biomarkers should not only correlate with pathological changes but also with disease stage and progression.

Frequency and Longitudinal Course of Motor Signs in Genetic Frontotemporal Dementia.

Background And Objectives: Frontotemporal dementia (FTD) is a highly heritable disorder. The majority of genetic cases are caused by autosomal dominant pathogenic variants in the chromosome 9 open reading frame 72 (), progranulin (), and microtubule-associated protein tau () gene. As motor disorders are increasingly recognized as part of the clinical spectrum, the current study aimed to describe motor phenotypes caused by genetic FTD, quantify their temporal association, and investigate their regional association with brain atrophy.

[Regression in Young Adults with Down-Syndrome: A Case Series].

Background: Regression in young adults with Down syndrome can present itself with an acute loss of acquired skills and change in behavior. The aim of our case series was to describe the heterogeneous clinical presentation of this syndrome as well as accompanying diagnostic and therapeutic challenges and consequences.

Methods: All three patients were assessed with the CAMDEX-DS (Cambridge Examination for Mental Disorders of Older People with Down Syndrome and Others with Intellectual Disabilities) and the criteria published by the DSMIG-USA (Down-Syndrome Medical Interest Group USA).

Serum Beta-Synuclein Is Higher in Down Syndrome and Precedes Rise of pTau181.

This exploratory case-control study investigates the synaptic marker beta-synuclein in serum and plasma pTau181 in adults with Down syndrome (DS) with (sDS, n = 14) and without (aDS, n = 47) clinical symptoms of Alzheimer disease (AD) as well as euploid controls (n = 23). Beta-synuclein was higher in aDS and more pronounced in sDS (p < 0.0001), whereas pTau181 was only higher in sDS (p < 0.

Impact of Partial Volume Correction on [F]GE-180 PET Quantification in Subcortical Brain Regions of Patients with Corticobasal Syndrome.

Corticobasal syndrome (CBS) is a rare neurodegenerative condition characterized by four-repeat tau aggregation in the cortical and subcortical brain regions and accompanied by severe atrophy. The aim of this study was to evaluate partial volume effect correction (PVEC) in patients with CBS compared to a control cohort imaged with the 18-kDa translocator protein (TSPO) positron emission tomography (PET) tracer [F]GE-180. Eighteen patients with CBS and 12 age- and sex-matched healthy controls underwent [F]GE-180 PET.

Utility of the Repeat and Point Test for Subtyping Patients With Primary Progressive Aphasia.

Background: Primary progressive aphasia (PPA) may present with three distinct clinical sybtypes: semantic variant PPA (svPPA), nonfluent/agrammatic variant PPA (nfvPPA), and logopenic variant PPA (lvPPA).

Objective: The aim was to examine the utility of the German version of the Repeat and Point (R&P) Test for subtyping patients with PPA.

Method: During the R&P Test, the examiner reads out aloud a noun and the participants are asked to repeat the word and subsequently point to the corresponding picture.

Dual-Phase β-Amyloid PET Captures Neuronal Injury and Amyloidosis in Corticobasal Syndrome.

In recent years several F-labeled amyloid PET (Aβ-PET) tracers have been developed and have obtained clinical approval. There is evidence that Aβ-PET perfusion can provide surrogate information about neuronal injury in neurodegenerative diseases when compared to conventional blood flow and glucose metabolism assessment. However, this paradigm has not yet been tested in neurodegenerative disorders with cortical and subcortical affection.

Motor speech disorders in the nonfluent, semantic and logopenic variants of primary progressive aphasia.

Objective: Motor speech disorders (MSDs) are characteristic for nonfluent primary progressive aphasia (nfvPPA). In primary progressive aphasia (PPA) of the semantic (svPPA) and of the logopenic type (lvPPA), speech motor function is considered typically intact. However, knowledge on the prevalence of MSDs in svPPA and lvPPA is mainly based on studies with a priori knowledge of PPA syndrome diagnosis.

Low-degree trisomy 21 mosaicism promotes early-onset Alzheimer disease.

Trisomy-21 mosaicism (mT21) with subclinical intellectual development disorder or physical phenotype has very rarely been associated with early-onset cognitive decline. Notably, early-onset Alzheimer's disease (EOAD) patients' family histories frequently suggest genetic causes other than autosomal-dominant APP/PSEN-1/2 mutations. We present an EOAD patient in his late fifties newly diagnosed with low-degree mT21 (13%/21% blood lymphocytes/ectodermal cells).

[Cognition in Down's Syndrome: Development across the Life Span and Neuropsychological Assessment in Adults].

Down's syndrome is the most frequent genetic cause of intellectual disability. As the risk for developing Alzheimer's disease is increased in Down's syndrome, comprehensive cognitive examination is essential, both in young adults (for baseline evaluation), as well as later for diagnosing dementia. So far, there are only a few recommendations for neuropsychological assessment in Down's syndrome.

Detection Gap of Right-Asymmetric Neuronal Degeneration by CERAD Test Battery in Alzheimer's Disease.

: Asymmetric disease characteristics on neuroimaging are common in structural and functional imaging of neurodegenerative diseases, particularly in Alzheimer's disease (AD). However, a standardized clinical evaluation of asymmetric neuronal degeneration and its impact on clinical findings has only sporadically been investigated for F-18-fluorodeoxyglucose positron emission tomography (F-18-FDG-PET). This study aimed to evaluate the impact of lateralized neuronal degeneration on the detection of AD by detailed clinical testing.

Cognitive reserve hypothesis in frontotemporal dementia: A FDG-PET study.

Background And Objective: Reserve is defined as the ability to maintain cognitive functions relatively well at a given level of pathology. Early life experiences such as education are associated with lower dementia risk in general. However, whether more years of education guards against the impact of brain alterations also in frontotemporal dementia (FTD) has not been shown in a large patient collective.

In Vivo Assessment of Neuroinflammation in 4-Repeat Tauopathies.

Background: Neuroinflammation has received growing interest as a therapeutic target in neurodegenerative disorders, including 4-repeat tauopathies.

Objectives: The aim of this cross-sectional study was to investigate 18 kDa translocator protein positron emission tomography (PET) as a biomarker for microglial activation in the 4-repeat tauopathies corticobasal degeneration and progressive supranuclear palsy.

Methods: Specific binding of the 18 kDa translocator protein tracer F-GE-180 was determined by serial PET during pharmacological depletion of microglia in a 4-repeat tau mouse model.

[A German version of the Cambridge examination for mental disorders of older people with Down's syndrome and others with intellectual disabilities : A diagnostic procedure for detecting dementia in people with Down's syndrome].

Background: Although people with Down's syndrome (DS) are at a high risk of developing an Alzheimer type dementia (AD) due to a triplication of the amyloid precursor gene, there are practically no internationally available test procedures to detect cognitive deficits in this at risk population in the German language.

Objective: The aim was to provide a German translation and intercultural adaptation of the Cambridge examination for mental disorders of older people with Down's syndrome and others with intellectual disabilities (CAMDEX-DS), which is available in English and Spanish. This instrument for diagnostics and monitoring consists of a psychological test examination (CAMCOG-DS) and a caregiver interview.

Neuronal injury biomarkers for assessment of the individual cognitive reserve in clinically suspected Alzheimer's disease.

Objectives: Many predictive or influencing factors have emerged in investigations of the cognitive reserve model of patients with Alzheimer's disease (AD). For example, neuronal injury, which correlates with cognitive decline in AD, can be assessed by [F]-fluorodeoxyglucose positron-emission-tomography (FDG-PET), structural magnetic resonance imaging (MRI) and total tau in cerebrospinal fluid (CSF), all according to the A/T/N-classification. The aim of this study was to calculate residual cognitive performance based on neuronal injury biomarkers as a surrogate of cognitive reserve, and to test the predictive value of this index for the individual clinical course.

Clinical Routine FDG-PET Imaging of Suspected Progressive Supranuclear Palsy and Corticobasal Degeneration: A Gatekeeper for Subsequent Tau-PET Imaging?

F-18-fluordeoxyglucose positron emission tomography (FDG-PET) is widely used for discriminative diagnosis of tau-positive atypical parkinsonian syndromes (T+APS). This approach now stands to be augmented with more specific tau tracers. Therefore, we retrospectively analyzed a large clinical routine dataset of FDG-PET images for evaluation of the strengths and limitations of stand-alone FDG-PET.

Atrophy in the Thalamus But Not Cerebellum Is Specific for FTD and ALS Patients - An Atlas-Based Volumetric MRI Study.

The neuropathology of patients with frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS) due to a mutation is characterized by two distinct types of characteristic protein depositions containing either TDP-43 or so-called dipeptide repeat proteins that extend beyond frontal and temporal regions. Thalamus and cerebellum seem to be preferentially affected by the dipeptide repeat pathology unique to mutation carriers. This study aimed to determine if mutation carriers showed an enhanced degree of thalamic and cerebellar atrophy compared to sporadic patients or healthy controls.

Additive value of amyloid-PET in routine cases of clinical dementia work-up after FDG-PET.

Purpose: In recent years, several [F]-labeled amyloid-PET tracers have been developed and have obtained clinical approval. Despite their widespread scientific use, studies in routine clinical settings are limited. We therefore investigated the impact of [F]-florbetaben (FBB)-PET on the diagnostic management of patients with suspected dementia that was still unclarified after [F]-fluordeoxyglucose (FDG)-PET.

[Amyloid positron-emission-tomography with [ F]-florbetaben in the diagnostic workup of dementia patients].

Background: To this day the definite diagnosis of Alzheimer's disease still relies on post-mortem histopathological detection of neurofibrillary tangles and beta-amyloid deposits. Amyloid positron emission tomography (PET) is a new diagnostic tool that enables the in vivo quantification of pathological beta-amyloid deposits. The aim of the current study was to evaluate to what extent F-florbetaben-PET (FBB-PET) influences the diagnosis of patients with dementia.