Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring最新文献

Introduction: Both micro- and macrostructural white matter (WM) abnormalities, particularly those related to axonal degeneration, are associated with cognitive decline in adults with Down syndrome (DS) prior to a diagnosis of Alzheimer disease. Neurofilament light chain (NfL) is a support protein within myelinated axons released into blood following axonal damage. In this study we investigated cross-sectional relationships between WM microstructural changes as measured by diffusion tensor imaging (DTI) and plasma NfL concentration in adults with DS without dementia.

Methods: Thirty cognitively stable (CS) adults with DS underwent diffusion-weighted MRI scanning and plasma NfL measurement. DTI measures of select WM tracts were derived using automatic fiber tracking, and associations with plasma NfL were assessed using Spearman correlation coefficients.

Results: Higher Plasma NfL was associated with greater altered diffusion measures of select tracts.

Discussion: Early increases in plasma NfL may reflect early white matter microstructural changes prior to dementia in DS.

Highlights: The onset of such WM changes in DS has not yet been widely studied.WM microstructural properties correlated with plasma neurofilament light chain (NfL).NfL may reflect early, selective WM changes in adults with DS at high risk of developing AD.

Introduction: We evaluated short versions of a 16-item odor identification (OID) test, with regard to their ability to identify individuals at high dementia risk.

Methods: Participants from the population-based SNAC-K study (n = 2418) were followed across 12 years. We formed 13 abbreviated clusters based on the identifiability and perceptual characteristics of the Sniffin' Sticks Test (SST) items, and pre-existing test versions. Dementia hazard was estimated with Cox regressions.

Results: Lower OID scores were associated with an increased dementia hazard across all odor clusters. Lower performance in the high identifiability cluster showed the strongest association with dementia (hazard ratio = 1.39, 95% confidence interval [1.28-1.51]). Moreover, the high-intensity odor cluster showed a stronger association with dementia than the low-intensity cluster (P = 0.02).

Discussion: The findings suggest that the SST items differ with regard to their association with dementia and support using a reduced set size for clinical practice.

Highlights: Odor identification (OID) items differ in their association with future dementia.Reduced OID set sizes render hazard ratios comparable to larger set sizes.Identifiability and perceptual characteristics of odors should be considered when designing dementia screening instruments.

Introduction: With the advent of disease-modifying therapies, accurate assessment of biomarkers indicating the presence of disease-associated amyloid beta (Aβ) pathology becomes crucial in patients with clinically suspected Alzheimer's disease (AD). We evaluated Aβ levels in cerebrospinal fluid (Aβ CSF) and Aβ levels in positron emission tomography (Aβ PET) biomarkers in a real-world memory-clinic setting to develop an efficient algorithm for clinical use.

Methods: Patients were evaluated for AD-related Aβ pathology from two independent cohorts (Ludwig Maximilian University [LMU], n = 402, and Medical University of Vienna [MUV], n = 144). Optimal thresholds of CSF biomarkers were deduced from receiver operating characteristic curves and validated against Aβ PET positivity.

Results: In both cohorts, a CSF Aβ42/40 ratio ≥ 7.1% was associated with a low risk of a positive Aβ PET scan (negative predictive value: 94.3%). Implementing two cutoffs revealed 14% to 16% of patients with intermediate results (CSF Aβ42/40 ratio: 5.5%-7.1%), which had a strong benefit from Aβ PET imaging (44%-52% Aβ PET positivity).

Discussion: A two-cutoff approach for CSF Aβ42/40 including Aβ PET imaging at intermediate results provides an effective assessment of Aβ pathology in real-world settings.

Highlights: We evaluated cerebrospinal fluid (CSF) and positron emission tomography (PET) amyloid beta (Aβ) biomarkers for Alzheimer's disease in real-world cohorts.A CSF Aβ 42/40 ratio between 5.5% and 7.1% defines patients at borderline levels.Patients at borderline levels strongly benefit from additional Aβ PET imaging.Two-cutoff CSF Aβ 42/40 and PET will allow effective treatment stratification.

Background: Recent advancements in Alzheimer's disease (AD) biomarker research and clinical trials prompt reflection on the value and consequently appropriate use of tau positron emission tomography (tau-PET) in the future.

Methods: We conducted an online survey among dementia and PET experts worldwide to investigate the anticipated future role of tau-PET in clinical practice and trials.

Results: Two hundred sixty-eight dementia experts, comprising 143 clinicians and 121 researchers, covering six continents participated. The vast majority (90%) fostered a positive attitude toward the added value of tau-PET in clinical practice, particularly for staging, diagnosing, monitoring, and prognostication in a cognitively impaired memory clinic population. Experts anticipated an important role for tau-PET for participant selection (76%-100%) and measuring endpoints (75%-97%), in both anti-amyloid and anti-tau drug trials.

Discussion: Our global survey study shows that dementia experts envision an important role for tau-PET in the future, both in clinical practice and in drug trials, beyond current guidelines and practices.

Highlights: Dementia experts envision an important role for tau-PET in the future.Experts indicate that a tau-PET scan could influence patient management.Experts anticipate the utility of tau-PET for participant selection and endpoints in drug trials.There is a gap between the anticipated usefulness of tau-PET and current clinical practices.

Introduction: Providing medical advice regarding lifestyle changes is currently the most effective intervention for delaying dementia onset among individuals with subjective cognitive decline (SCD). Adherence to such advice can be influenced by individual's social environment. We measured that impact within a Latinamerican population.

Methods: We recruited 183 SCD individuals from a Memory Clinic, analyzed their health-related, and provided them with medical advice. We assessed personal network composition and its healthy habits. We evaluated adherence to medical advice 6 months later.

Results: The proportion of heavy drinkers in the network is a risk factor to reduce alcohol consumption (odds ratio [OR] = 31.2, 95% confidence interval [CI] [3.73,301], p = 0.002), poor diets in the network hinders improving diet (p < 0.001 OR = 74.1, 95% CI [14.7,471]), and sedentary people in the network make it difficult to start exercising (OR = 4.92 95% CI [1.39,18.8], p = 0.016).

Discussion: Personal networks have an inertial effect, as relationships engaged in an unhealthy habit lower the probability of individuals to quit that habit.

Introduction: This study investigated the changes in functional capacity with disease progression in a well-characterised cohort of patients diagnosed with frontotemporal dementia (FTD) and Alzheimer's disease (AD) presentations.

Methods: We recruited 126 behavioural variant FTD (bvFTD), 40 progressive nonfluent aphasia (PNFA), 64 semantic dementia (SD), 45 logopenic progressive aphasia (LPA), and 115 AD patients. Functional capacity was measured annually over ∼7 years using the Disability Assessment for Dementia.

Results: Linear mixed effects models revealed the bvFTD group demonstrated disproportionate functional impairment at baseline and over the study period. Functional capacity among the other syndromes showed a more uniform pattern of decline, with less severe functional impairment at baseline and ∼7%-10% mean annual decline. Baseline correlations indicated different mechanisms supporting basic and complex functional proficiency among the groups.

Discussion: Our findings demonstrate distinct functional profiles across dementia syndromes with disease progression. Identifying progression milestones across syndromes will improve clinical management.

Highlights: bvFTD shows severe functional impairment at baseline and over time.PNFA, SD, LPA, AD: less severe baseline functional impairment; more uniform decline.General cognition is related to IADLs, but not BADLs, in all groups.Behavioural disturbances relate to IADLs and BADLs in bvFTD and SD.Behavioural-ADL relations are more mixed in PNFA, LPA, and AD.

Introduction: The hippocampus atrophies with age and is implicated in neurodegenerative disorders including Alzheimer's disease (AD). We examined the interplay between age and apolipoprotein E (APOE) genotype on total hippocampal volume.

Methods: Using neuroimaging data from 37,463 UK Biobank participants, we applied linear regression to quantify the association of age and APOE with hippocampal volume and identified the age when volumes of ε2/ε3, ε3/ε4, and ε4/ε4 carriers significantly deviated from ε3/ε3 using generalized additive modeling.

Results: Total hippocampal volume declined with age, with significant differences by APOE genotype emerging after age 60. ε3/ε4 and ε4/ε4 carriers displayed reduced volumes from ages 69 and 61, respectively, while ε2/ε3 showed delayed decline starting at the age of 76.

Discussion: The association of APOE and hippocampal volume is age-dependent, with differences in volumes of ε4/ε4 carriers detected as early as age 61. This work underscores the importance of APOE genotype in determining when to begin screening for AD.

Highlights: Apolipoprotein E (APOE) genotype shows an age-dependent association with total hippocampal volume.No association between APOE and total hippocampal volume was detected before age 60.Accelerated decline was observed in ε4/ε4 carriers at age 61 and ε3/ε4 at age 69.Delayed decline was evident in ε2/ε3 carriers starting at age 76.

Introduction: Widowhood and divorce are extremely stressful life events that are associated with dementia, but the neurobiological underpinnings of this risk remain unknown. Amyloid beta (Aβ) load may explain influences of chronic stress, commonly seen in disruptive marital transitions, on cognitive decline.

Methods: We examined whether Aβ quantified by tracer uptake on positron emission tomography mediates associations between marital dissolution and executive functioning and episodic memory performance using data from 543 cognitively normal (CN) participants from the Alzheimer's Disease Neuroimaging Initiative.

Results: Marriage dissolution was associated with increased Aβ burden (β = 0.56; P = 0.015) and worse memory performance (β = -0.09; P = 0.003). Aβ levels were a significant mediator for the relationship between marriage dissolution and memory (average causal mediation effect = -0.007; P = 0.029).

Discussion: Findings suggest that stressful life events, such as the dissolution of one's marriage, might exert an effect on Alzheimer's disease proteinopathy, which may subsequently influence poor cognition.Highlights: Marital dissolution was associated with increased amyloid beta (Aβ) and memory declines.Aβ burden mediated associations between marital dissolution and memory.Findings were robust to potential non-linear influences of age.Mediation results were not observed when stratifying marital groups by sex.

Introduction: Associations between amyloid-tau-neurodegeneration (ATN) plasma biomarkers and cognition have not been characterized in adults with type 1 diabetes (T1D).

Methods: Using data from participants in the Glycemic Variability and Fluctuations in Cognitive Status in Adults with T1D (GluCog) study (N = 114), we evaluated associations between phosphorylated tau (pTau)181, pTau217, β-amyloid 42/40 ratio, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) and self-administered digital cognitive tests, adjusting for age, sex, education, comorbidities (e.g., kidney disease), and glycemic indices.

Results: Higher concentrations of pTau181 and GFAP were associated with slower responses on working memory tasks (pTau181: β = 0.261; p = 0.007; GFAP: β = 0.175, p = 0.036), and higher β-amyloid 42/40 ratio was associated with better vocabulary (β = 0.260, p = 0.009).

Discussion: Digital cognitive performance was associated with several ATN plasma biomarkers in T1D adults. Prospective studies are needed to understand the utility of these biomarkers in T1D.

Highlights: There is an increase in life expectancy for individuals with type 1 diabetes (T1D).Few studies investigate the relationship between T1D and neurodegeneration.We characterize the relation between ATN plasma biomarkers and cognitive function.Digital cognitive performance was associated with plasma biomarkers in T1D adults.

Introduction: The increasing use of Alzheimer's disease (AD) biomarkers has led to the recognition of a subgroup of non-AD amnestic mild cognitive impairment (aMCI) patients who have medial temporal hypometabolism on fluorodeoxyglucose-positron emission tomography (FDG-PET).

Methods: In this academic memory-clinic-based consecutive series, 16 non-AD aMCI patients and 28 AD controls matched for sex, age, and baseline Mini-Mental State Examination (MMSE) were followed for a median duration of 4.5 years. Our primary outcome was the MMSE decline rate over the subsequent years. We also determined the final diagnosis over time.

Results: FDG-PET showed more pronounced medial temporal hypometabolism in non-AD cases and more inferior parietal lobule hypometabolism in AD controls. MMSE decline was slower in non-AD (β = -0.51) than in AD (β = -2.00) patients. Five non-AD cases developed frontotemporal dementia years after symptom onset, and one developed dementia with Lewy bodies.

Discussion: Non-AD aMCI patients with medial temporal hypometabolism show slower cognitive decline.

Highlights: Non-AD aMCI with medial temporal hypometabolism shows slower cognitive decline than AD.FDG-PET revealed distinct metabolic patterns between non-AD aMCI and AD patients.Approximately one-third of non-AD aMCI cases developed frontotemporal dementia.Comprehensive diagnostic biomarkers are crucial for non-AD aMCI characterization.