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

Introduction: Apathy is a significant feature in Alzheimer's disease (AD) and subjective cognitive impairment (SCI), though its mechanisms are not well established.

Methods: An effort-based decision-making (EBDM) framework was applied to investigate apathy in 30 AD patients, 41 SCI participants, and 55 healthy controls (HC). Data were analyzed using a drift-diffusion model (DDM) to uncover latent psychological processes.

Results: SCI participants reported higher apathy than AD patients and HC. However, informant reports of apathy in AD patients were higher than self-reports and indicated significant apathy compared to HC. Both the AD and SCI groups showed reduced sensitivity to effort changes, linked to executive dysfunction in AD and apathy in SCI. Increased resting functional cortical connectivity with the nucleus accumbens (NA) was associated with higher apathy in SCI.

Discussion: These results highlight a similar disruption of EBDM in AD and SCI, differentially related to executive functioning in AD and apathy in SCI.

Highlights: This is the first study investigating apathy using an effort-based decision-making (EBDM) framework in Alzheimer's disease (AD) and subjective cognitive impairment (SCI).Self-reports underestimate apathy in AD patients when compared to informant reports and healthy controls (HC). SCI participants, in whom self and informant reports were more concordant, also showed higher degrees of apathy.Both AD and SCI groups showed reduced sensitivity to effort.Reduced sensitivity to effort correlates with executive dysfunction in AD and apathy, but not depression, in SCI.Increased nucleus accumbens (ventral striatum) connectivity with the frontoparietal network was associated with higher apathy scores in SCI.The results thus suggest that while AD and SCI can have similar deficits in EBDM, these deficits correlate with distinct clinical manifestations: executive dysfunction in AD and apathy in SCI.

Introduction: Neurofibrillary tangles (NFTs), a hallmark of tau pathology in Alzheimer's disease (AD), accumulate in the aging brain. However, some individuals remain cognitively intact despite high Braak (III-VI) stages, which characterize NFTs' accumulation.

Methods: We studied resistance and resilience to tau pathology by assessing Braak stages based on apolipoprotein E (APOE) alleles, sex, and age in a sample of 1932 cognitively intact individuals of European ancestry from the Alzheimer's Disease Sequencing Project (ADSP).

Results: Resistance, characterized by low (0-II) Braak stages, was observed in men and women younger than 85 years of age. Resilience, indicated by high (III-VI) Braak stages, increased significantly with age in both men and women for each APOE allele. It became more pronounced, with the proportion of high Braak stages exceeding 50% at 85 years and older in women, irrespective of the APOE allele.

Discussion: The identification of factors underlying resistance and resilience against AD-related pathologies is essential for promoting cognitively healthy aging.

Highlights: We investigated cognitive resistance and resilience to tau pathology in Alzheimer's disease (AD).This study included individuals who were not diagnosed with AD.Braak stages 0-II and III-VI were considered as a measure of resistance and resilience, respectively.Resistance was stronger at ages younger than 85 years in non-carriers of the apolipoprotein E (APOE) ε4 allele.Resilience increased with age for each APOE allele independently of sex.At age 85 years and older, high resilience (>50%) was observed in women regardless of the APOE allele.

Introduction: Instrumental activities of daily living (iADLs) increasingly involve technology (e.g., making payments online, texting). The current study examined the applicability and diagnostic accuracy of technology-based iADLs in those evaluated for Alzheimer's disease and related dementias (ADRD).

Methods: A total of 264 care partners of persons undergoing comprehensive interdisciplinary evaluations completed the Functional Activities Questionnaire and 11 technology-based iADL items.

Results: Technology-based iADLs applied to more than 80% of patients. Average dependence on technology-based items was overall less than for traditional iADLs. The addition of technology-based items to traditional iADL items slightly improved the ability to identify individuals with dementia. When considered separately, technology-based iADL items demonstrated comparable ability to distinguish between diagnostic stages.

Discussion: Technology use is common in older adults with ADRD for a range of daily activities. Accounting for technology use increases the content validity of existing iADL measures for the modern context and yields comparable diagnostic accuracy.

Highlights: Technology use is often integral to daily activity performance for individuals with Alzheimer's disease and related dementias (ADRD).Daily technologies, such as smartphones, were used frequently by those with ADRD.Many individuals were less dependent on technology activities than traditional activities.Adding technology questions slightly increased diagnostic accuracy for detecting dementia.

This study aimed to investigate the dementia risk associated with mild behavioral impairment (MBI) and its domains in older community-dwelling individuals. A total 4803 community-dwelling individuals aged over 55 years were followed for 4.5 years (ZARADEMP study). MBI was assessed according to the International Society to Advance Alzheimer's Research and Treatment (ISTAART) diagnostic criteria using the Geriatric Mental State (GMS). Odds ratios (OR) for incident dementia and Alzheimer's disease (AD) were determined using logistic regression models adjusted for potential confounders (such as age, disability, or vascular disease). In cognitively normal individuals, decreased motivation was the only MBI domain that was associated with an increased risk of all-cause dementia (OR: 2.30 [95% confidence interval {CI}: 1.16-4.61]) in multivariable analyses, although the increase in the risk of AD was not statistically significant. Our findings suggest that decreased motivation may be a phenotypic marker for individuals at risk of dementia. Further research is required to evaluate the association between MBI domains and different types of dementia.

Introduction: Eye movement alterations are effective biomarkers for Alzheimer's disease (AD). This study examines task-evoked pupillary responses (TEPRs) as potential biomarkers of the mild cognitive impairment (MCI), the symptomatic stage preceding AD.

Methods: The prospective cohort study included 213 MCI patients and 514 cognitively normal controls (CNs). Participants performed a prosaccade (PS) or antisaccade (AS) task while their eye movements were tracked using a Tobii Pro Spectrum system.

Results: The CNs showed unique TEPRs linked to better performance, characterized by larger baselines, greater PS target-onset variability, and smaller AS target-onset variability. Conversely, for MCI patients, better performance was linked to larger AS target-onset sizes. Furthermore, MCI patients displayed reduced dilation during the cue and target-onset periods compared to CNs.

Discussion: MCI patients showed altered pupillary response patterns associated with cognitive task performance, highlighting the potential of oculomotor changes as a biomarker for early cognitive decline.

Highlights: MCI patients displayed markedly smaller pupil dilation than CNs in response to cue and target stimuli.For MCI patients, larger pupil size upon target appearance during antisaccades correlated with better performance.Faster and more consistent prosaccades were linked to better performance in both groups.For MCI patients, the association between longer AS latencies and better performance was more pronounced than in CNs.Combined analysis of TEPRs and saccade performances in a sizeable cohort strengthens the generalizability of our findings to the broader MCI population.

Objective: The rise in dementia prevalence, particularly in lower- and middle-income countries (LMIC), places a significant burden on healthcare systems. However, comprehensive data on dementia hospital admissions are scarce.

Methods: We analyzed admission rates for dementia, cost of hospital admissions, lengths of hospital stay, and in-hospital deaths in 2010 and 2019 in Brazil.

Results: Admission rates declined from 19.7/100,000 inhabitants in 2010 to 14.6/100,000 in 2019. In-hospital mortality increased from 3.9% in 2010 to 8.8% in 2019, particularly for short-term stays. Although 9.6% of hospital admissions occurred in regions with lower economic power in 2010 and 10.4% in 2019, these regions had higher mortality, reaching 4.3% of in-hospital deaths in 2010 and 9.3% in 2019.

Conclusion: The observed trends, alongside sex and regional disparities, underscore the need for targeted investment in healthcare infrastructure and training to improve dementia care in LMIC.

Highlights: The rate of hospital admissions for dementia was similar in 2010 and 2019 in Brazil.The cost per hospital admission in 2010 decreased by 38.5% compared with 2019.There was an increase in short-term hospital stays for dementia in 2019 compared to 2010, accompanied by an increase in mortality rates for these short-term stays.While hospital admissions for dementia decreased in men and increased in women, the in-hospital mortality due to dementia increased for both sexes.

Introduction: We investigated the agreement between automated and gold-standard manual transcriptions of telephone chatbot-based semantic verbal fluency testing.

Methods: We examined 78 cases from the Screening over Speech in Unselected Populations for Clinical Trials in AD (PROSPECT-AD) study, including cognitively normal individuals and individuals with subjective cognitive decline, mild cognitive impairment, and dementia. We used Bayesian Bland-Altman analysis of word count and the qualitative features of semantic cluster size, cluster switches, and word frequencies.

Results: We found high levels of agreement for word count, with a 93% probability of a newly observed difference being below the minimally important difference. The qualitative features had fair levels of agreement. Word count reached high levels of discrimination between cognitively impaired and unimpaired individuals, regardless of transcription mode.

Discussion: Our results support the use of automated speech recognition particularly for the assessment of quantitative speech features, even when using data from telephone calls with cognitively impaired individuals in their homes.

Highlights: High levels of agreement were found between automated and gold-standard manual transcriptions of telephone chatbot-based semantic verbal fluency testing, particularly for word count.The qualitative features had fair levels of agreement.Word count reached high levels of discrimination between cognitively impaired and unimpaired individuals, regardless of transcription mode.Automated speech recognition for the assessment of quantitative and qualitative speech features, even when using data from telephone calls with cognitively impaired individuals in their homes, seems feasible and reliable.

Background: Intracranial arteriosclerosis and cerebral amyloid beta (Aβ) are both involved in the etiology of Alzheimer's disease (AD) dementia, but the direct link between these two pathologies remains elusive.

Methods: In 633 participants (mean age 69 years, 51% women) from the population-based Rotterdam Study, we quantified cerebral Aβ accumulation on amyloid positron emission tomography (PET). We assessed calcification of the intracranial internal carotid (ICAC) and vertebrobasilar arteries (VBAC) as proxies of arteriosclerosis on non-enhanced computed tomography (CT). Using logistic and linear regression, we studied the relationship of presence, burden, and type of calcification with the presence and burden of Aβ.

Results: We found no associations of ICAC [odds ratio (OR): 0.85, 95% confidence interval (CI): 0.43, 1.72] or VBAC [OR: 0.59, CI: 0.26, 1.24] with cerebral Aβ. The results did not vary across ICAC subtypes.

Discussion: Intracranial arteriosclerosis was not associated with cerebral Aβ, underscoring their independence in the etiology of AD dementia.

Highlights: Comprehensive assessment of intracranial arteriosclerosis (e.g., including subtypes).Intracranial arteriosclerosis in different arteries and cerebral Aβ are not related.Arteriosclerosis and Aβ likely influence Alzheimer's disease dementia independently.

Introduction: To detect early cognitive impairment in community-dwelling older adults, this study explored the viability of artificial intelligence (AI)-assisted linear acceleration and angular velocity analysis during walking.

Methods: This cross-sectional study included 879 participants without dementia (female, 60.6%; mean age, 73.5 years) from the 2011 Comprehensive Gerontology Survey. Sensors attached to the pelvis and left ankle recorded the triaxial linear acceleration and angular velocity while the participants walked at a comfortable speed. Cognitive impairment was determined using Mini-Mental State Examination scores. Deep learning models were used to discern the linear acceleration and angular velocity data of 12,302 walking strides.

Results: The models' average sensitivity, specificity, and area under the curve were 0.961, 0.643, and 0.833, respectively, across 30 testing datasets.

Discussion: AI-enabled gait analysis can be used to detect signs of cognitive impairment. Integrating this AI model into smartphones may help detect dementia early, facilitating better prevention.

Highlights: Artificial intelligence (AI)-enabled gait analysis can be used to detect the early signs of cognitive decline.This AI model was constructed using data from a community-dwelling cohort.AI-assisted linear acceleration and angular velocity analysis during gait was used.The model may help in early detection of dementia.