Financial Incapacity of Patients with Mild Alzheimer’s Disease: What Neurologists Need to Know about Where the Impairment Lies

Research in the last decade has focused on assessing financial capacity and incapacity mainly in old age, but new research has turned to address the question of how financial incapacity can be predicted by cognitive factors. The aim of this study was to identify which cognitive domains predict financial capacity and the relevant cognitive skills of patients with mild Alzheimer’s disease (AD) in order to assist neurologists in functional assessment and further patient referral. In this study, 109 patients diagnosed with mild AD were examined with a number of neuropsychological tests: Mini-Mental State Examination (MMSE), Functional Rating Scale for Symptoms of Dementia (FRSSD), Functional Cognitive Assessment Scale (FUCAS), Trail Making Test (TMT)-Part B, Rey-Osterrieth Complex Figure Test (ROCFT)-copy condition and delayed recall condition, Rey Auditory Verbal Learning Test (RAVLT), Boston Naming Test, Rivermead Behavioural Memory Test (RBMT), digit span forward and backward, WAIS-R digit symbol substitution test, Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS-15), and the Legal Capacity for Property Law Transactions Assessment Scale (LCPLTAS). LCPLTAS total score and relevant subdomains were best predicted only by the score of one item coming from MMSE: subtraction of serial sevens. This is the only measure of arithmetic testing in use for the Greek geriatric population. Financial capacity is severely impaired in the group of mild AD patients. In order to prevent financial exploitation cases, neurologists, neuropsychologists, psychiatrists, and geriatrists should pay close attention to the information from the relevant arithmetic question of MMSE, as it is one of the most widely administered screening tests in clinical settings.

Negative Symptom Domains Are Associated With Verbal Learning in Adolescents With Early Onset Psychosis

Background: Early-onset psychosis (EOP) is among the leading causes of disease burden in adolescents. Negative symptoms and cognitive deficits predicts poorer functional outcome. A better understanding of the association between negative symptoms and cognitive impairment may inform theories on underlying mechanisms and elucidate targets for development of new treatments. Two domains of negative symptoms have been described in adult patients with schizophrenia: apathy and diminished expression, however, the factorial structure of negative symptoms has not been investigated in EOP. We aimed to explore the factorial structure of negative symptoms and investigate associations between cognitive performance and negative symptom domains in adolescents with EOP. We hypothesized that (1) two negative symptom factors would be identifiable, and that (2) diminished expression would be more strongly associated with cognitive performance, similar to adult psychosis patients.Methods: Adolescent patients with non-affective EOP (n = 169) were included from three cohorts: Youth-TOP, Norway (n = 45), Early-Onset Study, Norway (n = 27) and Adolescent Schizophrenia Study, Mexico (n = 97). An exploratory factor analysis was performed to investigate the underlying structure of negative symptoms (measured with the Positive and Negative Syndrome Scale (PANSS)). Factor-models were further assessed using confirmatory factor analyses. Associations between negative symptom domains and six cognitive domains were assessed using multiple linear regression models controlling for age, sex and cohort. The neurocognitive domains from the MATRICS Consensus Cognitive Battery included: speed of processing, attention, working memory, verbal learning, visual learning, and reasoning and problem solving.Results: The exploratory factor analysis of PANSS negative symptoms suggested retaining only a single factor, but a forced two factor solution corroborated previously described factors of apathy and diminished expression in adult-onset schizophrenia. Results from confirmatory factor analysis indicated a better fit for the two-factor model than for the one-factor model. For both negative symptom domains, negative symptom scores were inversely associated with verbal learning scores.Conclusion: The results support the presence of two domains of negative symptoms in EOP; apathy and diminished expression. Future studies on negative symptoms in EOP should examine putative differential effects of these symptom domains. For both domains, negative symptom scores were significantly inversely associated with verbal learning.

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.

The Red and Orange Complex Subgingival Microbiome of Cognitive Impairment and Cognitively Normal Elderly with Periodontitis

Increasing evidence has shown an association between periodontitis and cognitive impairment. Subgingival microbiota play a great role in periodontitis pathogenesis. However, the correlation between the subgingival microbiome and cognitive impairment remains unclear. This study aimed to evaluate the red and orange complex subgingival microbiome of cognitively impaired and cognitively normal elderly Indonesian subjects with periodontitis. Twenty-eight elderly subjects diagnosed with periodontitis underwent two cognitive examinations using the Hopkins Verbal Learning Test and the Mini-Mental State Examination. Gingival crevicular fluid taken from the periodontal pocket, at a depth between 5 and 7 mm, using a paper point was used as the subgingival samples. The subgingival microbiome in the cognitive impairment group (n = 14) and cognitively normal group (n = 14) was compared using the 16S rRNA Metagenomic iSeq™ 100 Sequencing System. There was β-diversity in the subgingival microbiota between the cognitively impaired and cognitively normal subjects. The metagenomic analysis showed a higher abundance of Porphyromonas and Treponema bacteria in the cognitive impairment group than in the normal cognitive group (p < 0.05). The abundance of Porphyromonas gingivalis and Treponema denticola was higher in the cognitively impaired elderly subjects. The role of P. gingivalis and T. denticola in the pathogenesis of cognitive impairment needs further investigation.

Speech Perception in Noise Is Associated With Different Cognitive Abilities in Chinese-Speaking Older Adults With and Without Hearing Aids

Chinese-speaking older adults usually do not perceive a hearing problem until audiometric thresholds exceed 45 dB HL, and the audiometric thresholds of the average hearing-aid (HA) user often exceed 60 dB HL. The purpose of this study was to examine the relationships between cognitive and hearing functions (measured as audiometric or speech reception thresholds) in older Chinese adults with HAs and with untreated hearing loss (HL). Participants were 49 Chinese older adults who used HAs and had moderate to severe HL (HA group), and 46 older Chinese who had mild to moderately severe HL but did not use HAs (untreated; or UT group). Multiple linear regression analysis was employed to evaluate how well age, education level, audiometric thresholds, and speech perception in noise were related to performance on general cognitive function, working memory, executive function, attention, and verbal learning tests. Results showed that speech perception in noise alone accounted for 13–25% of the variance in general cognitive function, working memory, and executive function in the UT group, and 9–21% of the variance in general cognitive function and verbal learning in the HA group (i.e., medium effect sizes). Audiometric thresholds did not explain any proportion of the variance in cognitive functioning in the HA or UT group. Thus, speech perception in noise accounts for more variance in cognitive performance than audiometric thresholds, and is significantly associated with different cognitive functions in older Chinese adults with HAs and with untreated HL.

Toward a Multimodal Computer-Aided Diagnostic Tool for Alzheimer’s Disease Conversion

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. It is one of the leading sources of morbidity and mortality in the aging population AD cardinal symptoms include memory and executive function impairment that profoundly alters a patient’s ability to perform activities of daily living. People with mild cognitive impairment (MCI) exhibit many of the early clinical symptoms of patients with AD and have a high chance of converting to AD in their lifetime. Diagnostic criteria rely on clinical assessment and brain magnetic resonance imaging (MRI). Many groups are working to help automate this process to improve the clinical workflow. Current computational approaches are focused on predicting whether or not a subject with MCI will convert to AD in the future. To our knowledge, limited attention has been given to the development of automated computer-assisted diagnosis (CAD) systems able to provide an AD conversion diagnosis in MCI patient cohorts followed longitudinally. This is important as these CAD systems could be used by primary care providers to monitor patients with MCI. The method outlined in this paper addresses this gap and presents a computationally efficient pre-processing and prediction pipeline, and is designed for recognizing patterns associated with AD conversion. We propose a new approach that leverages longitudinal data that can be easily acquired in a clinical setting (e.g., T1-weighted magnetic resonance images, cognitive tests, and demographic information) to identify the AD conversion point in MCI subjects with AUC = 84.7. In contrast, cognitive tests and demographics alone achieved AUC = 80.6, a statistically significant difference (n = 669, p &lt; 0.05). We designed a convolutional neural network that is computationally efficient and requires only linear registration between imaging time points. The model architecture combines Attention and Inception architectures while utilizing both cross-sectional and longitudinal imaging and clinical information. Additionally, the top brain regions and clinical features that drove the model’s decision were investigated. These included the thalamus, caudate, planum temporale, and the Rey Auditory Verbal Learning Test. We believe our method could be easily translated into the healthcare setting as an objective AD diagnostic tool for patients with MCI.

Adolescent Verbal Memory as a Psychosis Endophenotype: A Genome-Wide Association Study in an Ancestrally Diverse Sample

Verbal memory impairment is one of the most prominent cognitive deficits in psychosis. However, few studies have investigated the genetic basis of verbal memory in a neurodevelopmental context, and most genome-wide association studies (GWASs) have been conducted in European-ancestry populations. We conducted a GWAS on verbal memory in a maximum of 11,017 participants aged 8.9 to 11.1 years in the Adolescent Brain Cognitive Development Study®, recruited from a diverse population in the United States. Verbal memory was assessed by the Rey Auditory Verbal Learning Test, which included three measures of verbal memory: immediate recall, short-delay recall, and long-delay recall. We adopted a mixed-model approach to perform a joint GWAS of all participants, adjusting for ancestral background and familial relatedness. The inclusion of participants from all ancestries increased the power of the GWAS. Two novel genome-wide significant associations were found for short-delay and long-delay recall verbal memory. In particular, one locus (rs9896243) associated with long-delay recall was mapped to the NSF (N-Ethylmaleimide Sensitive Factor, Vesicle Fusing ATPase) gene, indicating the role of membrane fusion in adolescent verbal memory. Based on the GWAS in the European subset, we estimated the SNP-heritability to be 15% to 29% for the three verbal memory traits. We found that verbal memory was genetically correlated with schizophrenia, providing further evidence supporting verbal memory as an endophenotype for psychosis.

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.

Difference in Amyloid Load Between Single Memory Domain and Multidomain Subjective Cognitive Decline: A Study from the SILCODE

Background: Subjective cognitive decline (SCD), an at-risk condition of Alzheimer’s disease (AD), can involve various cognitive domains, such as memory, language, planning, and attention. Objective: We aims to explore the differences in amyloid load between the single memory domain SCD (sd-SCD) and the multidomain SCD (md-SCD) and assess the relationship of amyloid pathology with quantitative SCD scores and objective cognition. Methods: A total of 63 SCD participants from the SILCODE study underwent the clinical evaluation, neuropsychological assessment, and 18F-florbetapir PET scan. Global amyloid standard uptake value ratio (SUVr) was calculated. Additionally, regional amyloid SUVr was quantified in 12 brain regions of interests. A nonparametric rank ANCOVA was used to compare the global and regional amyloid SUVr between the md-SCD (n = 34) and sd-SCD (n = 29) groups. A multiple linear regression analysis was conducted to test the relationship of amyloid SUVr with quantitative SCD scores and objective cognition. Results: Compared with individuals with sd-SCD, individuals with md-SCD had increased global amyloid SUVr (F = 5.033, p = 0.029) and regional amyloid SUVr in the left middle temporal gyrus (F = 12.309, p = 0.001; Bonferroni corrected), after controlling for the effects of age, sex, and education. When pooling all SCD participants together, the increased global amyloid SUVr was related with higher SCD-plus sum scores and lower Auditory Verbal Learning Test-delayed recall scores. Conclusion: According to our findings, individuals with md-SCD showed higher amyloid accumulation than individuals with sd-SCD, suggesting that md-SCD may experience a more advanced stage of SCD. Additionally, increased global amyloid load was predictive of a poorer episodic memory function in SCD individuals.