Neuropsychological and neuroanatomical features of patients with behavioral variant Alzheimer's disease (AD): a comparison to behavioral variant frontotemporal dementia and amnestic AD groups

An understudied non-amnestic variant of Alzheimer's disease (AD), behavioral variant AD (bvAD) is associated with progressive personality, behavior, or executive dysfunction and frontal atrophy. This study characterizes the neuropsychological and neuroanatomical features associated with bvAD by comparing it to behavioral variant frontotemporal dementia (bvFTD), amnestic AD (aAD), and subjects with normal cognition. Subjects included 16 bvAD, 67 bvFTD, and 18 aAD patients, and 26 healthy controls. Compared to bvFTD, bvAD showed more significant visuospatial impairments (Rey Figure copy and recall), more irritability (Neuropsychological Inventory), and equivalent verbal memory (Philadelphia Verbal Learning Test). Compared to aAD, bvAD indicated more executive dysfunction (F-letter fluency) and better visuospatial performance. Neuroimaging analysis found that bvAD showed cortical thinning relative to bvFTD posteriorly in left temporal-occipital regions; bvFTD had cortical thinning relative to bvAD in left inferior frontal cortex. bvAD had cortical thinning relative to aAD in prefrontal and anterior temporal regions. All patient groups had lower volumes than controls in both anterior and posterior hippocampus. However, bvAD patients had higher average volume than aAD patients in posterior hippocampus and higher volume than bvFTD patients in anterior hippocampus after adjustment for age and intracranial volume. Findings demonstrated that underlying pathology mediates disease presentation in bvAD and bvFTD.

Comparison of Resting-State Brain Activation between Healthy Normal and Low Auditory-Verbal Working Memory Capacity Participants

Working memory (WM) capacity is the ability to maintain attention and store information briefly in the mind. However, each individual has a limited WM capacity that varies from one person to another. An individual can be categorized as having either normal or low WM capacity. This study aimed to evaluate and compare brain activations of healthy individuals with low and normal auditory-verbal WM capacity. A total of 39 healthy male young adults were recruited from local universities for this study. They were categorized into the normal and low auditory-verbal WM capacity group based on their score in the Malay Version of Auditory Verbal Learning Test (MVAVLT). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. The functional data were analyzed using Statistical Parametric Mapping (SPM) and Wake Forest University (WFU) Pickatlas softwares. Brain activations and resting-state amplitude fluctuation (rsAF) were contrasted between groups to determine whether there were any significant differences caused by the different auditory-verbal WM capacity. The findings indicated that the low auditory-verbal WM capacity group showed significantly higher cortical activations in the left lingual gyrus, bilateral middle temporal gyrus, left calcarine, left superior frontal gyrus, and left precuneus as compared to normal auditory-verbal WM capacity group. It is suggested that the higher activation of these brain areas in low verbal-auditory WM capacity participants was attributed to the lower neural adaptability of the brain at rest.

Comparing Map Learning between Touchscreen-Based Visual and Haptic Displays: A Behavioral Evaluation with Blind and Sighted Users

The ubiquity of multimodal smart devices affords new opportunities for eyes-free applications for conveying graphical information to both sighted and visually impaired users. Using previously established haptic design guidelines for generic rendering of graphical content on touchscreen interfaces, the current study evaluates the learning and mental representation of digital maps, representing a key real-world translational eyes-free application. Two experiments involving 12 blind participants and 16 sighted participants compared cognitive map development and test performance on a range of spatio-behavioral tasks across three information-matched learning-mode conditions: (1) our prototype vibro-audio map (VAM), (2) traditional hardcopy-tactile maps, and (3) visual maps. Results demonstrated that when perceptual parameters of the stimuli were matched between modalities during haptic and visual map learning, test performance was highly similar (functionally equivalent) between the learning modes and participant groups. These results suggest equivalent cognitive map formation between both blind and sighted users and between maps learned from different sensory inputs, providing compelling evidence supporting the development of amodal spatial representations in the brain. The practical implications of these results include empirical evidence supporting a growing interest in the efficacy of multisensory interfaces as a primary interaction style for people both with and without vision. Findings challenge the long-held assumption that blind people exhibit deficits on global spatial tasks compared to their sighted peers, with results also providing empirical support for the methodological use of sighted participants in studies pertaining to technologies primarily aimed at supporting blind users.

Análisis del desarrollo infantil en escolares de 5 a 6 años de zona rural y urbana de la Región del Bíobío, Chile (Analysis of child development in school children aged 5 to 6 in rural and urban areas of the Bíobío Region, Chile)

El estudio tuvo como objetivo analizar las diferencias en el desarrollo infantil en las dimensiones de motricidad, lenguaje, cognición y estado socioemocional en escolares de cinco y seis años pertenecientes a una escuela rural y otra urbana de la región del Biobío en Chile. El estudio fue observacional de corte transversal, con características descriptivas y analíticas. La muestra fue compuesta por 28 escolares de ambos sexos, distribuidos en siete niñas y siete niños de una zona rural (5.7±0.5 años) y siete niñas y siete niños de una zona urbana (5.6±0.6 años), seleccionada de forma no probabilística por conveniencia. Se evaluó el desarrollo infantil por medio del Test de Aprendizaje del Desarrollo Infantil (TADI). Los resultados muestran que existen diferencias significativas en los puntajes promedio de las dimensiones motriz y cognitiva (p˂0.05), con mejores resultados en los escolares de la zona rural. No hubo diferencias significativas en las dimensiones de lenguaje y estado socioemocional (p˃0.05), además se evidencia una relación positiva directa entre las dimensiones motriz y socioemocional para la zona urbana (p˂0.05). Se concluye que existen diferencias significativas en el desarrollo infantil entre los escolares pertenecientes a la zona rural y a la zona urbana, específicamente en las dimensiones motriz y cognitiva, con mejores resultados para los escolares de la zona rural. Abstract. The objective of the study was to analyze the differences in child development in the dimensions of motor skills, language, cognition, and socio-emotional state in five- and six-year-old school children belonging to a rural and an urban school in the Biobío region of Chile. The study was cross-sectional observational, with descriptive and analytical characteristics. The sample consisted of 28 school children of both sexes, seven girls and seven boys from rural areas (5.7 ± 0.5 years) and seven girls and seven boys from urban areas (5.6 ± 0.6 years) selected in a non-probabilistic way for convenience. Child development was assessed through the Child Development Learning Test (TADI). The results show that there are significant differences in the average scores of the motor and cognitive dimensions (p˂0.05), with better results in school children in rural areas. There were no significant differences in the dimensions of language and socio-emotional state (p˃0.05), in addition there was a direct positive relationship between the motor and socioemotional dimensions for the urban area (p˂0.05). Therefore, it is concluded that there are significant differences in child development between school children belonging to rural and urban areas, specifically in the motor and cognitive dimensions, with better results for school children in rural areas.

Sensory Impairment and Algorithmic Classification of Early Cognitive Impairment in Middle-Aged and Older Adults

Sensory function has been linked to cognitive impairment and dementia, but the link between multiple sensory impairments and early cognitive impairment (ECI) is unclear. Sensory function (vision, hearing, vestibular, proprioception, and olfaction) was measured in 390 BLSA participants (age=75±8 years; 57% women; 69% white) from 2012 to 2018 over a mean 3.6 years. ECI was defined based on 1 standard deviation below age-and race-specific means in Card Rotations or California Verbal Learning Test immediate recall. Cox proportional hazard models examined the risk of ECI for each sensory impairment and across categories of impairments. Vision impairment (vs. no vision impairment) was associated with a 70% greater risk of ECI (HR=1.70, p=0.05). Participants with 1 or ≥2 sensory impairments had triple the risk of ECI (HR=3.74 and 3.44, p=0.008 and 0.02, respectively) compared to those without impairment. Future studies are needed to examine whether treatment for sensory impairments can modify these risks.

Derivation and Validation of an Algorithmic Classification of Early Cognitive Impairment

The long prodromal period for dementia pathology demands valid and reliable approaches to detect cases before clinically recognizable symptoms emerge, by which time it may be too late to effectively intervene. We derived and compared several algorithms for early cognitive impairment (ECI) using longitudinal data on 1704 BLSA participants. Algorithms were based on cognitive impairment in various combinations of memory and non-memory tests, and the CDR. The best-performing algorithm was defined based on 1SD below age-and race-specific means in Card Rotations or California Verbal Learning Test immediate recall, two tests that in prior work show the earliest declines prior to dementia onset. While this ECI algorithm showed low concordance with concurrent adjudicated MCI/dementia (AUC: 0.63, sensitivity: 0.54, specificity: 0.73), it was among the best predictors of progression to MCI/dementia (HR: 3.65, 95% CI: 1.69,7.87). This algorithm may be useful in epidemiologic work to evaluate risk factors for early cognitive impairment.

Effect of Hypertension Duration and Blood Pressure Control During Early Adulthood on Cognitive Function in Middle Age

Background: Elevated blood pressure (BP) is a risk factor for cognitive impairment. Objective: We aim to explore the association between the duration of hypertension in early adulthood, with cognitive function in midlife. Furthermore, we investigate whether this asssociation is altered among participants with controlled BP. Methods: This prospective study included 2,718 adults aged 18–30 years without hypertension at baseline who participated in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Duration of hypertension was calculated based on repeat measurements of BP performed at 2, 5, 7, 10, 15, 20, and 25 years after baseline. Cognitive function was assessed at Year-25 using the Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and Stroop test. Results: After multivariable adjustment, a longer hypertension duration was associated with worse verbal memory (RAVLT, p trend = 0.002) but not with processing speed (DSST, p trend = 0.112) and executive function (Stroop test, p trend = 0.975). Among subgroups of participants with controlled (BP < 140/90 mmHg) and uncontrolled (SBP≥140 mmHg or DBP≥90 mmHg) BP at the time of cognitive assessment (i.e., Year-25 BP), longer duration of hypertension was associated with worse verbal memory. Similar results were observed in subgroups with controlled and uncontrolled average BP prior to cognitive assessment. Conclusion: Longer duration of hypertension during early adulthood is associated with worse verbal memory in midlife regardless of current or long-term BP control status. The potential risk of hypertension associated cognitive decline should not be overlooked in individuals with a long duration of hypertension, even if BP levels are controlled.

A Paradox in Digital Memory Assessment: Increased Sensitivity With Reduced Difficulty

The One Card Learning Test (OCL80) from the Cogstate Brief Battery—a digital cognitive test used both in-person and remotely in clinical trials and in healthcare contexts to inform health decisions—has shown high sensitivity to changes in memory in early Alzheimer's disease (AD). However, recent studies suggest that OCL sensitivity to memory impairment in symptomatic AD is not as strong as that for other standardized assessments of memory. This study aimed to improve the sensitivity of the OCL80 to AD-related memory impairment by reducing the test difficultly (i.e., OCL48). Experiment 1 showed performance in healthy adults improved on the OCL48 while the pattern separation operations that constrain performance on the OCL80 were retained. Experiment 2 showed repeated administration of the OCL48 at short retest intervals did not induce ceiling or practice effects. Experiment 3 showed that the sensitivity of the OCL48 to AD-related memory impairment (Glass's Δ = 3.11) was much greater than the sensitivity of the OCL80 (Glass's Δ = 1.94). Experiment 4 used data from a large group of cognitively normal older adults to calibrate performance scores between the OCL80 and OCL48 using equipercentile equating. Together these results showed the OCL48 to be a valid and reliable test of learning with greater sensitivity to memory impairment in AD than the OCL80.

Gut Microbiota and Mycobiota Evolution Is Linked to Memory Improvement after Bariatric Surgery in Obese Patients: A Pilot Study

Patients with obesity are known to exhibit gut microbiota dysbiosis and memory deficits. Bariatric surgery (BS) is currently the most efficient anti-obesity treatment and may improve both gut dysbiosis and cognition. However, no study has investigated association between changes of gut microbiota and cognitive function after BS. We prospectively evaluated 13 obese patients on anthropometric data, memory functions, and gut microbiota-mycobiota before and six months after BS. The Rey Auditory Verbal Learning Test (AVLT) and the symbol span (SS) of the Weschler Memory Scale were used to assess verbal and working memory, respectively. Fecal microbiota and mycobiota were longitudinally analyzed by 16S and ITS2 rRNA sequencing respectively. AVLT and SS scores were significantly improved after BS (AVLT scores: 9.7 ± 1.7 vs. 11.2 ± 1.9, p = 0.02, and SS scores: 9.7 ± 23.0 vs. 11.6 ± 2.9, p = 0.05). An increase in bacterial alpha-diversity, and Ruminococcaceae, Prevotella, Agaricus, Rhodotorula, Dipodascus, Malassezia, and Mucor were significantly associated with AVLT score improvement after BS, while an increase in Prevotella and a decrease in Clostridium, Akkermansia, Dipodascus and Candida were linked to SS scores improvement. We identified several changes in the microbial communities that differ according to the improvement of either the verbal or working memories, suggesting a complex gut-brain-axis that evolves after BS.