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BackgroundAlzheimer's disease, the most common cause of dementia, causes a progressive and irreversible deterioration of cognition that can sometimes be difficult to diagnose, leading to suboptimal patient care.MethodsWe developed a predictive model that computes multi-regional statistical morpho-functional mesoscopic traits from T1-weighted MRI scans, with or without cognitive scores. For each patient, a biomarker called "Alzheimer's Predictive Vector" (ApV) was derived using a two-stage least absolute shrinkage and selection operator (LASSO).ResultsThe ApV reliably discriminates between people with (ADrp) and without (nADrp) Alzheimer's related pathologies (98% and 81% accuracy between ADrp - including the early form, mild cognitive impairment - and nADrp in internal and external hold-out test sets, respectively), without any a priori assumptions or need for neuroradiology reads. The new test is superior to standard hippocampal atrophy (26% accuracy) and cerebrospinal fluid beta amyloid measure (62% accuracy). A multiparametric analysis compared DTI-MRI derived fractional anisotropy, whose readout of neuronal loss agrees with ADrp phenotype, and SNPrs2075650 is significantly altered in patients with ADrp-like phenotype.ConclusionsThis new data analytic method demonstrates potential for increasing accuracy of Alzheimer diagnosis.

Objectives: We assessed the modulation of allostatic load (AL) by engagement in healthy habits and life stressors, mediated through resilience and the perceived influence of the stressors. Sleep was included as third mediator given extensive evidence associating to all the analysed factors. Methods: Structural equation models to assess the modulation of AL by either traumatic or psychosocial stressors and healthy habits were generated with data from 620 mid-life adults (age 51.3 ± 5.48 years). Model 1 included self-reported life stressors, engagement in cognitive and physical activities, resilience and a pyramid score for diet. In Model 2, self-reported sleep quality was included in the mediation analysis between resilience and perceived stress on AL. Results: Direct effects of sports and diet on AL, and on resilience by sports were found in all the evaluated models. The modulation of AL by both types of stressors was only revealed in model 2, through indirect effects of perceived influence via sleep quality. An effect of sport habits on AL via resilience was found to be mediated by sleep, and equivalent but opposed effects of perceived influence of stressors and resilience on sleep quality emerged as critical factor for AL modulation. Conclusion: Our results suggest that sleep plays a pivotal role in the modulation of AL by both life stressors and sport habits, balancing the harmful and protective effects of perceived stress and resilience. The relative weight of one over the other to worsen or improve sleep quality will determine the resulting level of AL. [ABSTRACT FROM AUTHOR]

Identifying disease-specific imaging features of idiopathic Normal Pressure Hydrocephalus (iNPH) is crucial to develop accurate diagnoses, although the abnormal brain anatomy of patients with iNPH creates challenges in neuroimaging analysis. We quantified cortical thickness and volume using FreeSurfer 7.3.2 in 19 patients with iNPH, 28 patients with Alzheimer's disease (AD), and 30 healthy controls (HC). We noted the frequent need for manual correction of the automated segmentation in iNPH and examined the effect of correction on the results. We identified statistically significant higher proportion of volume changes associated with manual edits in individuals with iNPH compared to both HC and patients with AD. Changes in cortical thickness and volume related to manual correction were also partly correlated with the severity of radiological features of iNPH. We highlight the challenges posed by the abnormal anatomy in iNPH when conducting neuroimaging analysis and emphasise the importance of quality checking and correction in this clinical population. [ABSTRACT FROM AUTHOR]

Brain atrophy and cortical thinning are typically observed in people with Alzheimer's disease (AD) and, to a lesser extent, in those with mild cognitive impairment. In asymptomatic middle‐aged apolipoprotein ε4 (ΑPOE4) carriers, who are at higher risk of future AD, study reports are discordant with limited evidence of brain structural differences between carriers and non‐carriers of the ε4 allele. Alternative imaging markers with higher sensitivity at the presymptomatic stage, ideally quantified using typically acquired structural MRI scans, would thus be of great benefit for the detection of early disease, disease monitoring and subject stratification. In the present cross‐sectional study, we investigated textural properties of T1‐weighted 3T MRI scans in relation to APOE4 genotype, age and sex. We pooled together data from the PREVENT‐Dementia and ALFA studies focused on midlife healthy populations with dementia risk factors (analysable cohort: 1585 participants; mean age 56.2 ± 7.4 years). Voxel‐based and texture (examined features: contrast, entropy, energy, homogeneity) based morphometry was used to identify areas of volumetric and textural differences between APOE4 carriers and non‐carriers. Textural maps were generated and were subsequently harmonised using voxel‐wise COMBAT. For all analyses, APOE4, sex, age and years of education were used as model predictors. Interactions between APOE4 and age were further examined. There were no group differences in regional brain volume or texture based on APOE4 carriership or when age × APOE4 interactions were examined. Older people tended to have a less homogeneous textural profile in grey and white matter and a more homogeneous profile in the ventricles. A more heterogeneous textural profile was observed for females in areas such as the ventricles, frontal and parietal lobes and for males in the brainstem, cerebellum, precuneus and cingulate. Overall, we have shown the absence of volumetric and textural differences between APOE4 carriers and non‐carriers at midlife and have established associations of textural features with ageing and sex. [ABSTRACT FROM AUTHOR]

BackgroundMultiple gaming apps exist under the dementia umbrella for skills such as navigation; however, an app to specifically investigate the role of hearing loss in the process of cognitive decline is yet to be designed. There is a demonstrable gap in the utilization of games to further the knowledge of the potential relationship between hearing loss and dementia. ObjectiveThis study aims to identify the needs, facilitators, and barriers in designing a novel auditory-cognitive training gaming app. MethodsA participatory design approach was used to engage key stakeholders across audiology and cognitive disorder specialties. Two rounds, including paired semistructured interviews and focus groups, were completed and thematically analyzed. ResultsA total of 18 stakeholders participated, and 6 themes were identified to inform the next stage of app development. These included congruence with hobbies, life getting in the way, motivational challenge, accessibility, addictive competition, and realism. ConclusionsThe findings can now be implemented in the development of the app. The app will be evaluated against outcome measures of speech listening in noise, cognitive and attentional tasks, quality of life, and usability.

INTRODUCTION: Entorhinal cortex (EC) is the first cortical region to exhibit neurodegeneration in Alzheimer's disease (AD), associated with EC grid cell dysfunction. Given the role of grid cells in path integration (PI)–based spatial behaviors, we predicted that PI impairment would represent the first behavioral change in adults at risk of AD. METHODS: We compared immersive virtual reality (VR) PI ability to other cognitive domains in 100 asymptomatic midlife adults stratified by hereditary and physiological AD risk factors. In some participants, behavioral data were compared to 7T magnetic resonance imaging (MRI) measures of brain structure and function. RESULTS: Midlife PI impairments predicted both hereditary and physiological AD risk, with no corresponding multi‐risk impairment in episodic memory or other spatial behaviors. Impairments associated with altered functional MRI signal in the posterior‐medial EC. DISCUSSION: Altered PI may represent the transition point from at‐risk state to disease manifestation in AD, prior to impairment in other cognitive domains. [ABSTRACT FROM AUTHOR]