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

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.

Introduction: Smartphones are proving useful in assessing movement and speech function in Alzheimer's disease and other neurodegenerative conditions. Valid outcomes across different smartphones are needed before population-level tests are deployed. This study introduces the TapTalk protocol, a novel app designed to capture hand and speech function and validate it in smartphones against gold-standard measures.

Methods: Twenty different smartphones collected video data from motor tests and audio data from speech tests. Features were extracted using Google Mediapipe (movement) and Python audio analysis packages (speech). Electromagnetic sensors (60 Hz) and a microphone acquired simultaneous movement and voice data, respectively.

Results: TapTalk video and audio outcomes were comparable to gold-standard data: 90.3% of video, and 98.3% of audio, data recorded tapping/speech frequencies within ± 1 Hz of the gold-standard measures.

Discussion: Validation of TapTalk across a range of devices is an important step in the development of smartphone-based telemedicine and was achieved in this study.

Highlights: TapTalk evaluates hand motor and speech functions across a wide range of smartphones.Data showed 90.3% motor and 98.3% speech accuracy within +/-1 Hz of gold standards.Validation advances smartphone-based telemedicine for neurodegenerative diseases.

Introduction: It is unclear whether inflammation, that is, high interleukin-6 (IL-6) levels, and genetic risk, that is, apolipoprotein E (APOE) ε4 allele, have a compounding effect on cognitive decline (CD).

Methods: We analyzed a subset of participants from the longitudinal cohort study, Chicago Health and Aging Project, comprising 1120 biracial community-dwelling older adults (60% Black and 62% women), and mean follow-up = 6.4 years. We ran adjusted mixed-effects models on2 longitudinal CD.

Results: In APOE ε4 carriers, higher serum IL-6 was not associated with the rate of CD (β = -0.0091 [standard deviation (SD) = 0.0165, p = 0.5800]). Conversely, in non-ε4 carriers, compared to the lower tertile, those with the upper tertile of serum IL-6 levels experienced significantly accelerated CD (β = -0.0257 [SD = 0.0084, p = 0.0023]).

Discussion: Even without the largest genetic risk factor for late-onset Alzheimer's disease/Alzheimer's disease and related dementias (AD/ADRD), elevated serum IL-6 still accelerate the rate of CD in non-APOE ε4 carriers. Hence, interventions ameliorating inflammation may prevent AD/ADRD.

Highlights: Interleukin-6 (IL-6) and the apolipoprotein E (APOE) ε4 allele have been separately associated with an increased risk for cognitive decline, but their interaction remains unclear.In ε4 carriers, IL-6 was not associated with cognitive decline. However, even without the biggest genetic risk factor for Alzheimer's disease (AD), that is, APOE ε4, elevated serum IL-6 still could confer accelerated rate of cognitive decline, with a detrimental effect half of that imposed by APOE ε4 alone.We found no racial differences in these associations.These findings contribute complementary evidence on non-APOE ε4-dependent and non-AD biological pathways through which cognitive decline can still be accelerated in non-APOE ε4 carriers and highlight a specific subgroup of older adults who are at a higher risk of AD and thus may benefit from anti-inflammatory interventions.

Introduction: Adverse psychosocial exposure is associated with increased pro-inflammatory gene expression and reduced type-1 interferon gene expression known as the conserved transcriptional response to adversity (CTRA). CTRA is not well-studied in cognitive impairment but may contribute to late-life cognitive decline.

Methods: We examined perceived stress, loneliness, well-being, and the impact of coronavirus disease 2019 (COVID-19) and the relationship to the expression of genes associated with the CTRA. Mixed-effect linear models were used to quantify associations between psychosocial variables and CTRA gene expression.

Results: Eudaimonic well-being (EWB) was inversely associated with CTRA gene expression in participants with both normal cognition (NC) and mild cognitive impairment (MCI). Self-reported coping strategies differed by cognitive status and variably impacted CTRA gene expression.

Discussion: EWB is an important correlate of stress, even in people with MCI. The prodromal cognitive decline appears to moderate the significance of coping strategies as a correlate of CTRA gene expression.

Highlights: Conserved transcriptional response to adversity (CTRA) gene expression is higher with lower eudaimonic well-being.Eudaimonic well-being was important in both participants with normal cognition and those with mild cognitive impairment.Coping strategies and impact on CTRA gene expression differed by cognitive status.Loneliness in a population with relatively low loneliness scores did not impact CTRA gene expression.

Introduction: In 2018, the World Health Organization recognized traditional healers as community stakeholders in dementia care. This scoping review aimed to summarize the existing dementia care literature regarding strategies for the integration of traditional healing in dementia care and the roles of traditional healers.

Methods: A group of Indigenous Elders from Northern Ontario, Canada, guided, reviewed, and validated the research process and findings. The Joanna Briggs Institute approach was applied to a structured search strategy across the CINAHL, Embase, MEDLINE, and PsycINFO databases. A title and abstract screening were completed, followed by a full-text assessment of the identified manuscripts.

Results: A total of 143 full manuscripts were reviewed, of which two studies fully met the community-determined inclusion/exclusion criteria.

Discussion: The integration of traditional healing practices into dementia care offers a pathway to culturally-safe care for people with dementia. The findings identified policy advocacy as key to engage, educate, and empower traditional healers.

Highlights: The WHO recognized traditional healers as community stakeholders in dementia care and prevention worldwide in 2018; however, traditional healers are underrepresented and marginalized in healthcare systems due to the lack of culturally-safe dementia care (CSDC) policies at community and national levels globally.Community-based CSDC models were critically reviewed and validated by local Indigenous community stakeholder consultations.The result is a call to action to assist the WHO and Alzheimer's Disease International in developing guidelines for CSDC policy improvements with the global Indigenous community for the engagement and empowerment of traditional healers to navigate dementia care and to implement the WHO Global Action Plan on the Public Health Response to Dementia (2017-2025).Integration of Western biomedical and Indigenous traditional healing and medicine in dementia care in the healthcare system can reduce health disparities and empower traditional healers on a global scale. Indigenous-led models that include traditional healers in dementia care are critical for improving equity gaps in dementia care for Indigenous Peoples.