Journal of Alzheimer's Disease最新文献

BackgroundThe Digital Assessment of Cognition (DAC) is a brief, 7-minute iPad administered-scored neuropsychological protocol.ObjectiveThe current research sought to investigate relationships between DAC test results and family ratings for neurocognitive decline; instrumental activities of daily living (IADL) impairment; psychiatric symptoms, and physician-determined cardiovascular risks.Methods179 memory clinic patients were assessed. Family members rated the severity of neurocognitive impairment, IADL decline, and psychiatric symptoms using the Everyday Cognition Scales (ECog); the Functional Assessment Questionnaire (FAQ); the Instrumental Activities of Daily Living-Compensation Scale (IADL-C); and the Neuropsychiatric Inventory (NPI), respectively. An index measuring cardiovascular risk was extracted from medical records.ResultsPartial correlations controlled for age, education, and sex found that greater functional disability and elevated cardiovascular risks were associated with lower DAC memory and executive index scores. Lower DAC memory scores were seen in relation to family ratings suggesting impaired Ecog Episodic Memory difficulty; relatively intact ECog Executive/Attention ability; and impaired IADL-C Memory/Self-Management difficulty. By contrast, lower DAC executive performance was seen in relation to family ratings suggesting impaired Ecog Executive/Planning difficulty and IADL-C Social Skills difficulty. Lower DAC-executive index scores were also associated with greater informant rated apathy.ConclusionsThe relations between DAC index scores and total informant FAQ and IADL-scores; Ecog and IADL-C subscales; and selected NPI-defined psychiatric problems suggest that the DAC is both sensitive to gross IADL decline, and specific to differing ECog and IADL-C and psychiatric problems. Combining digital assessment with family IADL ratings could help with clinical decision-making.

BackgroundThe yes-no reversal (YNR) phenomenon consists in a patient saying "yes" when meaning "no", or vice-versa.ObjectiveTo investigate the prevalence of the YNR phenomenon in mild cognitive impairment (MCI) and dementia across different neurodegenerative, chronic cerebrovascular, or mixed etiologies, and to explore its demographic and clinical correlates.MethodsInformants of N = 267 patients with MCI or dementia due to possible/probable Alzheimer's disease (AD; N = 164), frontotemporal lobar degeneration (N = 25), Lewy body disease (N = 18), mixed-i.e., AD and chronic cerebrovascular-etiologies (N = 37), Aβ-negative degenerative etiologies (N = 6), and chronic cerebrovascular disease (N = 17) were inquired on the occurrence of YNRs in everyday-life conversations. YNR+ and YNR- patients were compared on demographics (i.e., age, sex, education), disease duration (in months), disease severity (i.e., MCI versus dementia), etiology and total and subscale-/item-level Mini-Mental State Examination (MMSE) scores. A multiple logistic model was also run on the presence/absence of YNRs by addressing, as predictors, variables that yielded significance at an univariable level.ResultsThe YNR phenomenon was recorded in 23 patients (8.61%), all of them being demented (i.e., no MCI patient showed YNRs). YNR+ patients were younger and scored lower on Immediate recall and Language subscores of the MMSE. The prevalence of YNRs was higher in non-AD- (∼18%) versus AD-related (∼5%) etiologies. The effects of disease severity and etiology were confirmed by the multiple logistic model, while the others were not.ConclusionsThe YNR phenomenon is a clinical sign possibly associated with dementia due to non-AD etiologies.

BackgroundRepetitive behaviors (RB) are purposeless movements, speech, or routines performed without self-awareness or conscious intent.ObjectiveThe present study aims to investigate the prevalence and longitudinal changes of RB and to assess these symptoms in a large cohort of patients with frontotemporal lobar degeneration (FTLD)-associated syndromes using a newly developed caregiver-based questionnaire.MethodsThis was a longitudinal cohort study conducted in tertiary frontotemporal dementia research clinics. A total of 210 FTLD patients were included, 68 of whom had follow-up evaluation. RB were assessed through structured caregiver interviews. Compulsive/impulsive behaviors, stereotypies, and ritualistic behaviors were recorded. Univariate and multiple generalized linear models and generalized linear mixed models were used to estimate predictors and longitudinal changes associated with RB.ResultsRB were reported in 71% of patients, showing a progressive increase from the prodromal to moderate dementia stages. Notably, 30% of patients presented RB since the disease onset phase, especially in the form of compulsive/impulsive behaviors. Predictors included male gender, the behavioral variant of frontotemporal dementia and the semantic variant of primary progressive aphasia phenotypes, and higher scores on Frontal Behavioral Inventory scale, part B. A significant increase in total RB was observed in patients reassessed at 8 to 22 months follow-up from baseline (p = 0.0001), especially in the form of stereotypies and ritualistic behaviors.ConclusionsThe questionnaire developed in this study effectively captures the prevalence and progression of RB. It could contribute to the standardization of the behavioral assessment in FTLD clinical trials and, consequently, to a deeper understanding of these syndromes.

BackgroundEducation promotes cognitive reserve (CR), potentially buffering Alzheimer's disease pathology (ADP). However, the education-CR relationship may differ by population and genetic background.ObjectiveTo examine education, APOE ε4, and functional scores in a Puerto Rican (PR) cohort with varying plasma pTau181, an ADP biomarker.MethodsA subset of 514 PR older adults with "high" (>mean+1SD) or "low" pTau181 (APOE ε4 strata. A secondary analysis applied a hurdle model, examining years of education as a continuous predictor on (1) the odds of any impairment (CDR-FUNC > 0) and (2) severity among impaired participants, adjusting for age and sex.ResultsHigh EA was associated with better CDR-FUNC than low EA within the high pTau181 group (n = 80; Median_{Low_EA} = 7, Median_{High_EA} = 0; p = 0.011). The hurdle model similarly showed that each additional year of education reduced the odds of any functional impairment in the high-pTau181 group (OR = 0.89, 95% CI [0.79-0.99]). No significant education × APOE ε4 interaction was observed, though a negative trend suggested that increasing education attenuated ε4-related impairment.ConclusionsGreater education is linked to functional preservation in PR older adults, particularly in those with elevated ADP, suggesting potential CR-mediated resilience. APOE ε4 may worsen outcomes with decreasing education, suggesting both educational and genetic factors should inform strategies to mitigate cognitive decline globally.

BackgroundGenomic research in dementia in Africa is of utmost importance based on recent reports from studies on African-Americans that the African ancestral gene is associated with a lower risk effect for developing AD. However, dementia-related genetic studies are still evolving in sub-Saharan Africa, with unique challenges influencing participant recruitment.ObjectiveThis study sought to identify key challenges of recruitment and retention how they were mitigated in the READD-ADSP Africa and 'Origins of AD in African ancestry' genetic studies.MethodsA qualitative narrative research design using in-depth interviews explored the challenges of recruiting participants and how these were managed by the nineteen stakeholders involved in the recruitment process from nine African countries participating in the African Dementia Consortium. An inductive thematic analysis was applied to code and analyze the data systematically.ResultsNineteen stakeholders from nine African countries, participating in READD-ADSP and 'Origins' studies were interviewed. Similar challenges were observed across most African countries, including the non-existing national dementia registry. Other challenges include language diversity, myths around blood collection, family dynamics, stigma, logistics, unmet expectations concerning incentives, fewer older controls and data privacy. Leveraging previous research programs, existing community engagement activities and client-doctor relationships were strategies used in addressing these challenges.ConclusionsThere are some unique challenges with recruiting and retaining participants in genetic studies in Africa. Strengthening community engagement and advocacy for genomic research, alongside a well-populated dementia registry in the African Dementia Consortium, could overcome these challenges and improve participant recruitment in genetic studies.

BackgroundA healthy lifestyle supports cognitive aging while reducing dementia risk. Multidomain interventions promote healthy behavior, but are often unsuccessful in reaching those with a low socio-economic position (SEP), who face additional challenges with changing behavior.ObjectiveThis cross-sectional study explores differences between SEP-groups in dementia risk, lifestyle, and the socio-cognitive determinants of behavior.Methods3,341 Dutch adults (aged 40-79) were divided into low, medium, or high SEP groups. Using Chi-squared tests and ANOVA, SEP-related differences were explored for dementia risk, lifestyle behaviors, and health conditions. SEP-related differences in socio-cognitive determinants were examined using a modified version of Confidence Interval-Based Estimation of Relevance (CIBER).ResultsParticipants in the low SEP group had a significantly higher prevalence of all health conditions and engaged in more unhealthy behaviors, translating into a significantly higher dementia risk score. Many had misperceptions about the room for lifestyle improvement, but those in the low SEP group were slightly more aware of not adhering to lifestyle recommendations. Additionally, they perceived less self-confidence towards engaging in sports, considered healthy food as more expensive, perceived alcohol less pleasurable, experienced habits as less influential on alcohol intake, and had less confidence in their ability to quit smoking while pleasure and habits were strongly associated with smoking.ConclusionsAdults with a low SEP are at higher risk for dementia and have more potential for lifestyle-based risk reduction. Tailored, co-designed interventions that also consider the broader environment are needed to enhance perceived behavioral control, support behavior change, and reduce inequalities in dementia.

BackgroundEmerging studies implicate the microtubule-associated protein tau as a key modulator of neuronal excitability and synaptic dysfunction in human tauopathies. How distinct tau forms influence synaptic excitability across brain regions with differing susceptibility to tau accumulation remains unclear. Primary age-related tauopathy (PART), defined by hippocampal-restricted tau pathology in the absence of amyloid-β, offers a tractable model to investigate tau-specific effects on synaptic physiology.ObjectiveTo determine how regionally enriched tau species in PART relate to synaptic excitation-inhibition balance and to identify molecular pathways linking tau oligomers to synaptic dysfunction.MethodsAutopsy-derived hippocampal and superior middle temporal gyrus tissues from neuropathologically validated PART specimens were analyzed. Tau species, including monomers, oligomers, and paired helical filaments (PHFs), were quantified by western blot. Synaptic function was assessed by microtransplantation of synaptosomal membranes into Xenopus laevis oocytes, followed by electrophysiological recordings of glutamatergic (kainate-evoked AMPAR) and GABAergic (GABA_AR) currents to calculate the synaptic excitation-to-inhibition (sE/I) ratio. Proteomic and enrichment analyses of brain-derived tau oligomer (BDTO) interactomes from PART hippocampi were performed.ResultsPART specimens showed hippocampal accumulation of aggregation-prone tau assemblies (oligomeric and PHF-tau) that were negatively correlated with sE/I. Proteins within the BDTO interactome linked to reduced sE/I were enriched for pathways related to vesicle-mediated transport, synaptic endocytosis, and neurotransmitter receptor regulation.ConclusionsIn PART, oligomeric and fibrillar tau are associated with shift toward synaptic inhibition, predominantly within the hippocampus. Proteomic correlates implicate vesicle trafficking pathways as mediators of tau oligomer-associated alterations in synaptic function, providing mechanistic insight into early-stage tauopathy.

BackgroundIn prior research, the Digital Assessment of Cognition (DAC), a brief digitally administered neuropsychological protocol that assesses verbal episodic memory, verbal working memory, and language, has been used to classify a small sample of memory clinic patients (n = 77) into four meaningful clinical groups.ObjectiveThe current research sought to extend these findings with a considerably larger sample.MethodsThe DAC was administered to 179 ambulatory care/memory clinic patients (45.30% female; 91.10% Caucasian). A comprehensive analysis of DAC core outcome measures and behavior reflecting process/errors was undertaken. Traditional paper/pencil assessment was also obtained. Using Jak, Bondi criteria (2009), paper/pencil test results classified patients into five groups: cognitively unimpaired (CU; n = 74), subtle cognitive impairment (SCI; n = 21), amnestic mild cognitive impairment (aMCI; n = 21), combined dysexecutive/mixed MCI (dys/mxMCI; n = 22), and mild dementia (n = 41).ResultsThe aMCI group presented with many of the classic features consistent with amnesia, i.e., rapid forgetting, reduced free recall clustering, and profligate responding to recognition foils. Latency for correct recognition responding was slower for aMCI compared to the CU group and appears to be associated with a neurocognitive network measuring both memory and language-related operations. SCI and dys/mxMCI groups tended to produce more perseverations on working memory test trials; and produced lower scores on DAC executive outcome measures that assessed auditory span and semantic fluency.ConclusionsThese findings support the criterion and construct validity of the DAC. When brought to scale the DAC could be an effective tool to assess for emergent MCI and dementia syndromes.

Sensory impairments (e.g., decreased function in hearing, vision, olfaction, and other senses) may be risk factors for or early markers of Alzheimer's disease (AD) and related dementias (ADRD). Sensory impairments are common and have a large impact on wellbeing. Furthermore, they are clinically detectable and, often, treatable, and could be leveraged to identify and prevent AD/ADRD. This Supplemental Issue brings together original research articles, reviews, and thought papers regarding the links between sensory impairments and cognitive health. Together, this work highlights the significant opportunities to use sensory information and remediation for earlier diagnosis, treatment, and prevention of dementia.

BackgroundIn aging-related neurodegeneration, therapeutic interventions directed at defined protein targets have been launched. A key step has been developing diagnostic biological markers, followed by immunotherapy. These steps have been achieved for amyloid-β protein (Aβ).ObjectiveTo evaluate, based on brain pathology, how frequently Aβ would be detectable in blood or cerebrospinal fluid in older individuals.MethodsWe assessed brain tissue from 1825 deceased subjects, 20% of whom were demented. We examined the presence of Aβ, hyperphosphorylated τ (HPτ), Transactive DNA-binding protein 43 (TDP-43), and α-synuclein (αS) using immunohistochemistry. The extent of these alterations was assessed following current consensus criteria.ResultsThe combination of Aβ/HPτ, constituting Alzheimer's disease neuropathological change (ADNC), was detected in 64% of subjects, increasing significantly (Pearson's Chi-Square p = 0.001) from 46% in the 5^th decade to 81% in the 9^th decade. In 506 subjects (28% of the cohort), intermediate or high levels of ADNC were observed an extent reported as assessable in cerebrospinal fluid. Among these, 235 were non-demented and would have been identified as being at risk of Alzheimer's disease. Most (74%) displayed concomitant pathologies, making it impossible at this stage to determine which pathology will eventually lead to cognitive impairment.ConclusionsCommon ADNC and frequent concomitant pathologies in older individuals will influence the interpretation of diagnostic biological tests. Current tests can confirm that a subject displays ADNC; however, a definite diagnosis can only be achieved through postmortem neuropathological assessment. Present diagnostic tests are too crude to detect early or low-level ADNC.