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

Introduction: Blood-based glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau (pTau) have shown promising prognostic potential in Alzheimer's disease (AD), but their applicability in clinical settings where comorbidities are prevalent remains uncertain.

Methods: Simoa assays quantified GFAP, NfL, and pTau181 in retrospectively retrieved prediagnostic serum samples from 102 AD patients and 21 non-AD controls.

Results: Higher serum GFAP levels predicted earlier clinical presentation and faster subsequent Mini-Mental State Examination decline in AD patients. Serum NfL levels were increased in patients with arterial hypertension (AHT), kidney dysfunction, and a history of stroke and only demonstrated predictive value for time to clinical AD presentation after adjustment for these comorbidities. Serum pTau181 instability during long-term storage at -20°C prevented its prognostic evaluation in retrospectively retrieved serum samples.

Discussion: Serum GFAP is a robust prognostic marker for AD progression, whereas NfL is impacted by various comorbidities, which complicates the interpretation of its prognostic value.

Highlights: Serum GFAP levels predict time to clinical AD presentation.Serum NfL levels are increased by hypertension, kidney disease, and stroke history.Prognostic value of serum NfL in AD is only evident after comorbidity correction.Serum levels of GFAP, but not NfL, increase over time within prediagnostic AD stages.

Introduction: Many persons with dementia are undiagnosed or unaware of dementia, which may affect hospitalization outcomes.

Methods: We evaluated differences in length of stay, days not at home, discharge destination, and 30-day readmissions over 1 year in 6296 older adults in the National Health and Aging Trends Study with linked Medicare claims. Multivariable-adjusted models compared outcomes across no dementia, undiagnosed dementia, unaware but diagnosed with dementia, and aware and diagnosed with dementia.

Results: Persons with undiagnosed dementia had longer length of stay and were more likely to be discharged to a facility (44.8% vs. 19.3%) compared to no dementia; differences persisted in multivariable models. Persons undiagnosed or unaware experienced outcomes similar to persons aware and diagnosed except for more 30-day readmissions in the undiagnosed (adjusted odds ratio [95% confidence interval] 2.05 [1.01, 4.16]).

Discussion: Persons undiagnosed or unaware of dementia experience worse hospitalization outcomes, suggesting potential clinically significant implications of unrecognized dementia.

Highlights: Persons with undiagnosed versus no dementia have worse hospitalization outcomes.Persons with undiagnosed dementia have more 30-day readmissions compared to persons diagnosed.Lack of clinician or family recognition of dementia may adversely affect hospitalization outcomes.

Introduction: The aim of the study was to estimate the population-based dementia incidence in Germany over a period of two decades.

Methods: We analyzed data from 4814 participants of the population-based Heinz Nixdorf Recall study (49.8% men, 45-75 years at baseline period 2000-2003), who have been monitored for the occurrence of cognitive decline and dementia. We calculated the cumulative incidence of dementia and its major subtypes and the incidence rate per 1000 person-years over two decades.

Results: During a median follow-up of 18.2 (Q1-Q3: 11.3-20.6) years, a total of 298 participants (6.2%) developed dementia (22.1% Alzheimer´s disease, 23.5% vascular dementia, 15.1% mixed dementia, 9.1% other dementia, 30.2% unspecified). The overall incidence rate was 3.9 per 1000 person-years.

Discussion: Our study is the only current population-based study in Germany that estimates the incidence of dementia. In order to reduce the high proportion of unspecific dementia diagnoses, diagnostics urgently need to be improved.

Highlights: New data on the incidence of dementia in Germany in participants ≥45 years of age.Participants have been monitored for dementia incidence over two decades.The overall incidence in our cohort was 3.9 per 1000 person-years.Many patients had unspecific dementia diagnoses in their medical records.Further diagnostic evaluation should be available for all dementia patients.

Introduction: Dementia is underdiagnosed in the United States. Understanding of older adults' experiences with screening is needed to optimize diagnosis.

Methods: US adults ages 65 to 80 (N = 1298) were surveyed on experiences with cognitive screening and blood biomarker (BBM) testing. Regression models estimated associations between characteristics and screening use.

Results: Most older adults were aware of screening (71%); 41% reported ever being screened. Older age, higher education, retirement, poorer health, and family history of dementia were associated with higher odds of screening; Hispanic and non-Hispanic Asian race/ethnicity were associated with lower odds (p < .05). Most older adults were unaware of BBM (81%); few wanted testing immediately (9%). Although older adults held positive views about screening and BBM, half reported concerns about distress or stigma if tests indicated risk.

Discussion: Cognitive screening rates remain low. Older adults view screening and BBM as useful to inform health decisions but have concerns about potential harms.

Highlights: Only one in five older US adults report having cognitive screening in the past year.Sociodemographic and health factors may influence whether older adults receive cognitive screening.Most older adults have positive views about cognitive screening and BBM testing.Many older adults would be concerned about distress or stigma if test result indicated dementia risk.

Subjective cognitive decline (SCD) may represent a preclinical manifestation of objective cognitive impairment. This review consolidated existing findings to determine if dual-tasks objectively differentiate between individuals with SCD, motoric cognitive risk syndrome (MCR), mild cognitive impairment (MCI), and dementia. MEDLINE, Embase, PsycINFO, CENTRAL, AgeLine, and CINAHL were systematically searched for dual-task studies examining older adults with SCD and analyzed using random-effects meta-analyses. Thirteen studies met the inclusion criteria. Within the SCD group, faster gait speed (SMD, 1.35; 95% CI, 0.57-2.13; p = .0007) and longer step length (SMD, 0.85; 95% CI, 0.44-1.26; p < .0001) favored the single compared to dual-task condition. Faster gait speed was observed in the SCD group compared to MCI (SMD, 0.48; 95% CI, 0.28-0.67; p = .0001). A standardized dual-task approach is needed to track gait parameters longitudinally, beginning with changes occurring at the SCD stage as these may precede future cognitive impairments.

Highlights: Evidence demonstrates that SCD may be a precursor to dementia.Faster dual-task gait speed was observed in the SCD group compared to MCI.Slower dual-task gait speed and shorter step length were observed within the SCD group.Dual-tasks may help differentiate between preclinical and clinical cognitive decline.Dual-tasks should be standardized and changes should be tracked longitudinally.

Introduction: Blood-based biomarkers seem promising for the diagnosis of Alzheimer's disease (AD).

Methods: We performed a systematic review and meta-analysis on the potential of blood phosphorylated Tau181 (p-tau181) to differentiate amyloid-positive (A+) and amyloid-negative (A-) subjects. Two meta-analyses were conducted, showing the mean p-tau values in blood and cerebrospinal fluid (CSF) in the A+ and A- group, and the second comparing the mean p-tau concentrations in blood and CSF among A+ versus A- participants, by laboratory assessment method.

Results: Eighteen studies (2764 A+ and 5646 A- subjects) were included. The single-group meta-analysis showed mean higher blood p-tau181 values in the A+ than in the A- group. In the head-to-head meta-analysis, blood p-tau reliably differentiated A+ patients from A- participants.

Discussion: Regardless of the laboratory technique, blood p-tau181 reliably differentiates A+ and A- subjects. Therefore, it might have important applications for early diagnosis and inclusion in clinical trials for AD patients.

Highlights: The role of blood-based biomarkers in discriminating AD patients is still uncertain.Blood p-tau181 distinguishes among amyloid-positive and amyloid-negative subjects.Blood p-tau181 might allow early diagnosis and inclusion in clinical trials.

Introduction: Studies have shown that blood biomarkers can differentiate dementia disorders. However, the diagnosis of dementia still relies primarily on cerebrospinal fluid and imaging modalities. The new disease-modifying treatments call for more widely applicable biomarkers.

Methods: Plasma samples (n = 250) from two mixed memory clinic were included. Participants were divided into amyloid beta positives (Aβ+) and Aβ negatives (Aβ-). Plasma phosphorylated tau (p-tau) 181, p-tau231, Aβ1-42 (Aβ42), Aβ40, Aβ42/Aβ40, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) were measured by single molecule array.

Results: Significant differences were found among cognitively unimpaired, mild cognitive impairment, Alzheimer's disease (AD), and non-AD, and nearly all of the biomarkers were able to predict amyloid status. When combining p-tau181 and p-tau231 they predicted Aβ positivity with an area under the curve (AUC) of 0.75, and when combining all biomarkers an AUC of 0.86 was found.

Discussion: This study supports previous findings on plasma biomarkers, even when investigated in a typical clinical setting in a consecutive, heterogeneous, mixed memory clinic.

Highlights: This study investigated seven plasma biomarkers in a mixed memory clinic, regardless of amyloid co-pathology or atypical phenotypes.These findings support previous promising results on plasma biomarkers, even when investigated in a heterogeneous population.The combination of phosphorylated tau (p-tau)181 and p-231 performed only slightly worse than a panel of multiple biomarkers, aligning with previous studies.Plasma biomarkers show potential for future applications in primary care, treatment monitoring, and trial selection.

Introduction: This study examined whether sex differences in verbal learning and memory (VLM) are mediated by plasma brain-derived neurotrophic factor (BDNF) expression.

Methods: In a sample of n = 201 participants (63.81 ± 6.04 years, 66.2% female, 65.7% family history of Alzheimer's disease [AD], 38% apolipoprotein E [APOE] ε4+) from the Wisconsin Registry for Alzheimer's Prevention, VLM was measured using trials 3 through 5 and delayed recall from the Rey Auditory Verbal Learning Test. Plasma BDNF was measured using a Human BDNF Quantikine Immunoassay. Mediation analysis used bootstrapping, and stratified mediation models tested the conditional dependence of APOE ε4 carriage.

Results: BDNF partially mediated the sex-VLM relationship (β = -0.07; 95% confidence interval [CI]: -0.18, -0.01). Female APOE ε4 carriers had higher VLM scores (β = -0.53; p = 0.03), while female non-carriers had both higher BDNF levels (β = -0.68; p < 0.01) and VLM scores (β = -1.06; p < 0.01); BDNF was again a significant mediator (β = -0.18; 95% CI: -0.37, -0.05).

Discussion: This study found that circulating BDNF mediates higher verbal memory scores in females-particularly in APOE ε4 non-carriers.

Highlights: Sex differences in verbal learning and memory (VLM) were mediated by plasma brain-derived neurotrophic factor (BDNF) levels.Women exhibited higher VLM scores and plasma BDNF levels compared to men.The protective effect of BDNF in women was attenuated by apolipoprotein E ε4 carriage.Findings suggest sex-specific mechanisms against verbal memory decline in aging.

Background: Late-life depression (LLD) is a heterogenous disorder related to cognitive decline and neurodegenerative processes, raising a need for the development of novel biomarkers. We sought to provide preliminary evidence for acoustic speech signatures sensitive to LLD and their relationship to depressive dimensions.

Methods: Forty patients (24 female, aged 65-82 years) were assessed with the Geriatric Depression Scale (GDS). Vocal features were extracted from speech samples (reading a pre-written text) and tested as classifiers of LLD using random forest and XGBoost models. Post hoc analyses examined the relationship between these acoustic features and specific depressive dimensions.

Results: The classification models demonstrated moderate discriminative ability for LLD with receiver operating characteristic = 0.78 for random forest and 0.84 for XGBoost in an out-of-sample testing set. The top classifying features were most strongly associated with the apathy dimension (R ² = 0.43).

Discussion: Acoustic vocal features that may support the diagnosis of LLD are preferentially associated with apathy.

Highlights: The depressive dimensions in late-life depression (LLD) have different cognitive correlates, with apathy characterized by more pronounced cognitive impairment.Acoustic speech features can predict LLD. Using acoustic features, we were able to train a random forest model to predict LLD in a held-out sample.Acoustic speech features that predict LLD are preferentially associated with apathy. These results indicate a predominance of apathy in the vocal signatures of LLD, and suggest that the clinical heterogeneity of LLD should be considered in development of acoustic markers.

Introduction: We explored associations between measurements of the ocular choroid microvasculature and Alzheimer's disease (AD) risk.

Methods: We measured the choroidal vasculature appearing in optical coherence tomography (OCT) scans of 69 healthy, mid-life individuals in the PREVENT Dementia cohort. The cohort was prospectively split into low-, medium-, and high-risk groups based on the presence of known risk factors (apolipoprotein E [APOE] ε4 genotype and family history of dementia [FH]). We used ordinal logistic regression to test for cross-sectional associations between choroidal measurements and AD risk.

Results: Choroidal vasculature was progressively larger between ordinal risk groups, and significantly associated with risk group prediction. APOE ε4 carriers had thicker choroids and larger vascularity compared to non-carriers. Similar trends were observed for those with a FH.

Discussions: Our results suggest a potential link between the choroidal vasculature and AD risk. However, these exploratory findings should be replicated in a larger sample.

Highlights: Ocular choroidal microvasculature is of interest in relation to neurodegeneration due to its autonomic response to systemic, pathophysiological change.Choroidal changes in the prodromal stage of Alzheimer's disease (AD) are unexplored.The PREVENT Dementia cohort offers a unique, non-invasive study of the microvasculature in mid-life individuals at increased risk for developing AD.Significantly increased ocular choroidal vasculature was associated with increased risk (apolipoprotein E carrier and/or family history of dementia) for AD.These exploratory results suggest a potential association between the ocular choroidal vasculature and AD risk. However, findings should be replicated in a larger sample.