The painter who changed her brain at the flick of a switch.

The study of artists with acquired brain damage is an empirical way to investigate the multiplicity of cerebral changes that occur with artistic training. We describe a talented painter with a left progressive cerebral lesion. In spite of losing function of her right hand, she regained dexterity of the left one in ten days for painting and drawing but not for writing. We discuss two potential explanations for her rapid recovery: (a) her extensive artistic training and/or (b) the slow-growing nature of her cerebral lesion.

Neural Basis of Long-term Musical Memory in Cognitively Impaired Older Persons.

OBJECTIVE: The objective of this study was to determine whether exposure to long-known music would evoke more extensive activation of brain regions minimally affected by Alzheimer disease (AD) pathology and outside traditional memory networks using a functional magnetic resonance imaging paradigm involving listening to long-known and recently-learned music in older adults with cognitive impairment to provide insight into mechanisms of long-term musical memory preservation in cognitively impaired older persons. METHODS: Seventeen subjects with a diagnosis of mild AD or mild cognitive impairment were recruited for this study. Subjects were scanned using functional magnetic resonance imaging while they performed a music listening task, which included short clips of personally selected music from the patient's past and newly-composed music heard for the first time 60 minutes before scanning. From this task, we obtained group-level maps comparing brain areas associated with long-known and recently-heard music in all subjects. RESULTS: Exposure to long-known music preferentially activated brain regions including the medial prefrontal cortex, precuneus, anterior insula, basal ganglia, hippocampus, amygdala, and cerebellum relative to recently-heard music. These areas are involved in autobiographical memory and associated emotional responses. In addition, they are minimally affected by early stage AD pathology, thus providing a neural basis for long-known musical memory survival. CONCLUSIONS: Long-known music activates a bilateral network of prefrontal, emotional, motor, auditory, and subcortical regions (cerebellum, putamen, limbic structures). This extensive activation, relative to recently-heard music, may offer structural and functional clues as to why long-term musical memory appears to be relatively preserved among cognitively impaired older persons.

Association Between Neuropsychiatric Symptom Trajectory and Conversion to Alzheimer Disease.

INTRODUCTION: Neuropsychiatric symptoms (NPS) are both common in mild cognitive impairment and Alzheimer disease (AD). Studies have shown that some NPS such as apathy and depression are a key indicator for progression to AD. METHODS: We compared Neuropsychiatric Inventory (NPI) total score and NPI subdomain score between mild cognitive impairment-converters (MCI-C) and mild cognitive impairment-nonconverters (MCI-NC) longitudinally for 6 years using the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. In addition to the NPI, Mini-Mental State Examination (MMSE) scores were also compared to find out if MMSE scores would differ between different NPI groups. Lastly, a linear regression model was done on MMSE and NPI total score to establish a relationship between MMSE and NPI total score. RESULTS: The results in this study showed that NPI total scores between MCI-C and MCI-NC differed significantly throughout 6 years. MCI-C subjects had a higher mean NPI total score and lower MMSE score compared with MCI-NC subjects. In addition, MMSE scores were significantly different between the 3 groups of NPI total score. Subjects who have a high NPI score have the lowest mean MMSE score, thus demonstrating that NPI scores do indeed affect MMSE scores. Further analyses using a regression model revealed that a unit change in NPI total score lead to 0.1 to 0.3 decrease in MMSE. DISCUSSION: On the basis of the findings, this study showed evidence that increase in NPS burden (reflected by increase in NPI) over time predicts conversion to AD, whereas stability of symptoms (reflected by stable NPI score) favors nonconversion. Further study should investigate the underlying mechanisms that drive both NPS burden and cognitive decline.

Do painters need their whole brain to excel?

Skilled professional artists are sometimes able to maintain their talents while other cognitive functions deteriorate due to brain diseases. The objective of this study is to asses the preserved artistry of a professional painter in spite of the presence of strokes affecting brain areas implicated in art expression. She had a neurologic evaluation and brain imaging after the stroke; painter-curators analyzed and compared the painter's pictorial artwork created before and after the stroke. In spite of cerebellar, visuospatial, motor, cognitive, and functional deficits likely related to strokes affecting bilateral cerebellar, left occipital, and right temporal-occipital areas, the patient was able to maintain most of their artistic painting skills.. After a short period of functional recovery, our patient showed discrepancy among their impaired cerebellar cerebral functions in day activities and their preserved painting abilities.

"Blue is music to my ears": multimodal synesthesias after a thalamic stroke.

Acquired synesthesias have been reported in association with deafferentation of the visual system, temporal lobe seizures, and the use of psychedelics. Based on our review of the literature, the appearance of synesthesias after a thalamic stroke has been reported only once. We present the case of a 45-year-old hypertensive male who, 9 months after a hemorrhagic stroke involving the left lateral posterior nucleus of the thalamus developed persistent sound-tactile, sound-color, and grapheme-gustatory synesthesias. Moreover, the patient noted that even thinking about a sensory stimulus could trigger the experience of another sensory modality, a conceptual type of synesthesia.

Correction: Valcic et al. Determining Whether Sex and Zygosity Modulates the Association between APOE4 and Psychosis in a Neuropathologically-Confirmed Alzheimer's Disease Cohort. Brain Sci. 2022, 12, 1266.

In the original publication [...].

Determining Whether Sex and Zygosity Modulates the Association between APOE4 and Psychosis in a Neuropathologically-Confirmed Alzheimer's Disease Cohort.

BACKGROUND: The APOE4 allele is a genetic risk factor for developing late-onset Alzheimer's disease (AD). Previous work by our group revealed that female APOE4 homozygotes with Lewy body (LB) pathology were more likely to experience psychosis compared to female APOE4 non-carriers, whereas in males there was no APOE4 dose-dependent significant effect. The objective of this study was to refine our previous findings by adjusting for covariates and determining the probability of an APOE4 sex-mediated effect on psychosis. METHODS: Neuropathologically confirmed AD patients with LB pathology (n = 491) and without LB pathology (n = 716) were extracted from the National Alzheimer's Coordinating Center (NACC). Patients were classified as psychotic if they scored positively for delusions and/or hallucinations on the Neuropsychiatric Inventory. Analysis consisted of a preliminary unadjusted binary logistic regression and a Generalized Additive binary logistic regression Model (GAM) to predict the relationship between APOE4 status and sex on the presence of psychosis in both cohorts, adjusting for age, education and MMSE. RESULTS: In the cohort with LB pathology, female APOE4 homozygotes were significantly more likely to experience psychosis compared to female APOE4 non-carriers (OR = 4.15, 95%CI [1.21, 14.2], p = 0.023). Female heterozygotes were also more likely to experience psychosis compared to female APOE4 non-carriers, but to a lesser extent (OR = 2.37, 95%CI [1.01, 5.59], p = 0.048). There was no significant difference in males with LB pathology or in any sex in the cohort without LB pathology. CONCLUSIONS: Sex and zygosity influence the effect of APOE4 on psychosis in neuropathologically confirmed AD patients, with the effect being limited to females with LB pathology.

Delusional Severity Is Associated with Abnormal Texture in FLAIR MRI.

Background: This study examines the relationship between delusional severity in cognitively impaired adults with automatically computed volume and texture biomarkers from the Normal Appearing Brain Matter (NABM) in FLAIR MRI. Methods: Patients with mild cognitive impairment (MCI, n = 24) and Alzheimer's Disease (AD, n = 18) with delusions of varying severities based on Neuropsychiatric Inventory-Questionnaire (NPI-Q) (1­mild, 2­moderate, 3­severe) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed for this task. The NABM region, which is gray matter (GM) and white matter (WM) combined, was automatically segmented in FLAIR MRI volumes with intensity standardization and thresholding. Three imaging biomarkers were computed from this region, including NABM volume and two texture markers called "Integrity" and "Damage". Together, these imaging biomarkers quantify structural changes in brain volume, microstructural integrity and tissue damage. Multivariable regression was used to investigate relationships between imaging biomarkers and delusional severities (1, 2 and 3). Sex, age, education, APOE4 and baseline cerebrospinal fluid (CSF) tau were included as co-variates. Results: Biomarkers were extracted from a total of 42 participants with longitudinal time points representing 164 imaging volumes. Significant associations were found for all three NABM biomarkers between delusion level 3 and level 1. Integrity was also sensitive enough to show differences between delusion level 1 and delusion level 2. A significant specified interaction was noted with severe delusions (level 3) and CSF tau for all imaging biomarkers (p < 0.01). APOE4 homozygotes were also significantly related to the biomarkers. Conclusion: Cognitively impaired older adults with more severe delusions have greater global brain disease burden in the WM and GM combined (NABM) as measured using FLAIR MRI. Relative to patients with mild delusions, tissue degeneration in the NABM was more pronounced in subjects with higher delusional symptoms, with a significant association with CSF tau. Future studies are required to establish potential tau-associated mechanisms of increased delusional severity.

Long-Known Music Exposure Effects on Brain Imaging and Cognition in Early-Stage Cognitive Decline: A Pilot Study.

BACKGROUND: Repeated exposure to long-known music has been shown to have a beneficial effect on cognitive performance in patients with AD. However, the brain mechanisms underlying improvement in cognitive performance are not yet clear. OBJECTIVE: In this pilot study we propose to examine the effect of repeated long-known music exposure on imaging indices and corresponding changes in cognitive function in patients with early-stage cognitive decline. METHODS: Participants with early-stage cognitive decline were assigned to three weeks of daily long-known music listening, lasting one hour in duration. A cognitive battery was administered, and brain activity was measured before and after intervention. Paired-measures tests evaluated the longitudinal changes in brain structure, function, and cognition associated with the intervention. RESULTS: Fourteen participants completed the music-based intervention, including 6 musicians and 8 non-musicians. Post-baseline there was a reduction in brain activity in key nodes of a music-related network, including the bilateral basal ganglia and right inferior frontal gyrus, and declines in fronto-temporal functional connectivity and radial diffusivity of dorsal white matter. Musician status also significantly modified longitudinal changes in functional and structural brain measures. There was also a significant improvement in the memory subdomain of the Montreal Cognitive Assessment. CONCLUSION: These preliminary results suggest that neuroplastic mechanisms may mediate improvements in cognitive functioning associated with exposure to long-known music listening and that these mechanisms may be different in musicians compared to non-musicians.

Neuropsychiatric Presentations due to Traumatic Brain Injury in Cognitively Normal Older Adults.

Neuropsychiatric symptoms (NPS) are common sequelae of traumatic brain injuries (TBI) among adults. However, little is known about NPS associated with a history of TBI in adults relative to adults without a history of TBI and to what extent NPS may be modulated by sex and other factors. Using the National Alzheimer's Coordinating Center Uniform Data Set, we examined the association between Neuropsychiatric Inventory-Questionnaire (NPI-Q) scores in cognitively normal older adults with and without a history of TBI. A binomial logistic regression model was used to examine NPI-Q domains in adults with a history of TBI (n = 266) versus without a history of TBI (n = 1508). History of TBI, sex, age, and body mass index were used as covariates. Adults with a history of TBI had a greater probability of exhibiting agitation, anxiety, apathy, disinhibition and aberrant motor behavior relative to adults without a history of TBI. In terms of sex differences, males with and without a history of TBI had an increased likelihood of agitation, apathy, disinhibition, and apnea, whereas females had an increased likelihood of anxiety and insomnia relative to males. Our study confirms that history of TBI is associated with an increased prevalence of specific NPS, including agitation, anxiety, apathy, disinhibition, and aberrant motor behavior. Given that the aforementioned NPS are linked through different pathways, damage to any of them may cause an alteration in behavior. As well, NPS appear to be modulated by sex, with symptoms differing between males and females. Our research suggests future studies examining NPS sequelae of TBI should adjust for sex.

An exploration of cognitive subgroups in Alzheimer's disease.

Heterogeneity is observed in the patterns of cognition in Alzheimer's disease (AD). Such heterogeneity might suggest the involvement of different etiological pathways or different host responses to pathology. A total of 627 subjects with mild/moderate AD underwent cognitive assessment with the Mini-Mental State Examination (MMSE) and the Dementia Rating Scale-2 (DRS-2). Latent class analysis (LCA) was performed on cognition subscale data to identify and characterize cognitive subgroups. Clinical, demographic, and genetic factors were explored for association with class membership. LCA suggested the existence of four subgroups; one group with mild and another with severe global impairment across the cognitive domains, one group with primary impairments in attention and construction, and another group with primary deficits in memory and orientation. Education, disease duration, age, Apolipoprotein E-epsilon4 (APOE epsilon4) status, gender, presence of grasp reflex, white matter changes, and early or prominent visuospatial impairment were all associated with class membership. Our results support the existence of heterogeneity in patterns of cognitive impairment in AD. Our observation of classes characterized by predominant deficits in attention/construction and memory respectively deserves further exploration as does the association between membership in the attention/construction class and APOE epsilon4 negative status.

Cerebrospinal Fluid Correlates of Neuropsychiatric Symptoms in Patients with Alzheimer's Disease/Mild Cognitive Impairment: A Systematic Review.

BACKGROUND: Neuropsychiatric symptoms (NPS) are common, accelerate the conversion to dementia, and are associated with increased caregiver burden in Alzheimer's disease (AD) and mild cognitive impairment (MCI). OBJECTIVE: The aim of this study is to identify potential associations between the core cerebrospinal fluid (CSF) biomarkers (amyloid/tau) and NPS in AD/MCI. METHODS: For this systematic review, four databases, PubMed (1946-2018), Cochrane (2005-2018), EMBASE (1947-2018), and PsycINFO (1806-2018) were searched for relevant observational studies using an extensive list of keywords. English studies were selected for critical appraisal based on our inclusion/exclusion criteria. Inclusion criteria were defined as 1) at least one AD CSF biomarker has been measured; 2) at least one NPS has been assessed; and 3) analysis has been done to examine the association between core AD CSF biomarker and NPS (main outcome). Animal, postmortem, and review studies were excluded. RESULTS: In total, 21 studies qualified for the systematic review. The overall picture regarding the association between NPS and AD CSF biomarkers is conflicting. However, agitation/aggression was significantly and consistently related to core AD CSF biomarkers. Moreover, depression was the only NPS to occasionally be associated with lower core AD CSF pathology. CONCLUSION: Our study has revealed agitation/aggression as the most consistent NPS related to core AD CSF biomarkers. Future studies are required to focus on other neglected NPS domains such as disinhibition. Moreover, why depression was the only NPS inversely associated with core AD CSF pathology remains to be elucidated. Our study also revealed a great degree of heterogeneity, hence calling for a more standardized "objective" approach for the evaluation of NPS.

Music Intervention Approaches for Alzheimer's Disease: A Review of the Literature.

Music interventions have been widely adopted as a potential non-pharmacological therapy for patients with Alzheimer's disease (AD) to treat cognitive and/or behavioral symptoms of the disease. In spite of the prevalence of such therapies, evidence for their effectiveness report mixed results in the literature. The purpose of this narrative review is to investigate the effectiveness of various intervention strategies (music therapy vs. music listening techniques) and music type used in the intervention (individualized vs. non-individualized music) on cognitive and behavioral outcomes for persons with AD. Databases were searched for studies using either active music therapy or music listening techniques over the last 10 years. These studies were in English, included persons with AD dementia, and whose protocol gathered pre- and post-intervention outcome measures. We initially identified 206 papers which were then reduced to 167 after removing duplicates. Further review yielded 13 papers which were extensively reviewed, resulting in a final sample of six papers. Our analysis of these papers suggested that, regardless of the music intervention approach, individualized music regimens provided the best outcomes for the patient. Furthermore, music listening may act as a relaxation technique and therefore provide a long-term impact for the patient, while active music therapy may acts to engage participants through social interaction and provide acute benefits. Our findings suggest that music techniques can be utilized in various ways to improve behavior and cognition.

Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease.

OBJECTIVE: To identify single-nucleotide polymorphisms (SNPs) associated with risk and age at onset of Alzheimer disease (AD) in a genomewide association study of 469 438 SNPs. DESIGN: Case-control study with replication. SETTING: Memory referral clinics in Canada and the United Kingdom. PARTICIPANTS: The hypothesis-generating data set consisted of 753 individuals with AD by National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria recruited from 9 memory referral clinics in Canada and 736 ethnically matched control subjects; control subjects were recruited from nonbiological relatives, friends, or spouses of the patients and did not exhibit cognitive impairment by history or cognitive testing. The follow-up data set consisted of 418 AD cases and 249 nondemented control cases from the United Kingdom Medical Research Council Genetic Resource for Late-Onset AD recruited from clinics at Cardiff University, Cardiff, Wales, and King's College London, London, England. MAIN OUTCOME MEASURES: Odds ratios and 95% confidence intervals for association of SNPs with AD by logistic regression adjusted for age, sex, education, study site, and French Canadian ancestry (for the Canadian data set). Hazard ratios and 95% confidence intervals from Cox proportional hazards regression for age at onset with similar covariate adjustments. RESULTS: Unadjusted, SNP RS4420638 within APOC1 was strongly associated with AD due entirely to linkage disequilibrium with APOE. In the multivariable adjusted analyses, 3 SNPs within the top 120 by P value in the logistic analysis and 1 in the Cox analysis of the Canadian data set provided additional evidence for association at P< .05 within the United Kingdom Medical Research Council data set: RS7019241 (GOLPH2), RS10868366 (GOLPH2), RS9886784 (chromosome 9), and RS10519262 (intergenic between ATP8B4 and SLC27A2). CONCLUSIONS: Our genomewide association analysis again identified the APOE linkage disequilibrium region as the strongest genetic risk factor for AD. This could be a consequence of the coevolution of more than 1 susceptibility allele, such as APOC1, in this region. We also provide new evidence for additional candidate genetic risk factors for AD that can be tested in further studies.

Hyper memory, synaesthesia, savants Luria and Borges revisited.

In this paper, we investigated two subjects with superior memory, or hyper memory: Solomon Shereshevsky, who was followed clinically for years by A. R. Luria, and Funes the Memorious, a fictional character created by J. L. Borges. The subjects possessed hyper memory, synaesthesia and symptoms of what we now call autistic spectrum disorder (ASD). We will discuss interactions of these characteristics and their possible role in hyper memory. Our study suggests that the hyper memory in our synaesthetes may have been due to their ASD-savant syndrome characteristics. However, this talent was markedly diminished by their severe deficit in categorization, abstraction and metaphorical functions. As investigated by previous studies, we suggest that there is altered connectivity between the medial temporal lobe and its connections to the prefrontal cingulate and amygdala, either due to lack of specific neurons or to a more general neuronal dysfunction.

Neste artigo, investigamos dois sujeitos com memória superior ou hipermemória: Solomon Shereshevsky, que foi seguido clinicamente por anos por A. R. Luria, e Funes o memorioso, um personagem fictício criado por J. L. Borges. Os sujeitos possuem hipermemória, sinestesia e sintomas do que hoje chamamos de transtorno do espectro autista (TEA). Vamos discutir interações dessas características e seu possível papel na hipermemória. Nosso estudo sugere que a hipermemória em nossos sujeitos sinestésicos pode ser devido às suas características de síndrome do TEA-savant. No entanto, esse talento foi acentuadamente diminuído pelo profundo déficit de categorização, abstração e funções metafóricas. Conforme investigado por estudos anteriores, sugerimos que há conectividade alterada entre o lobo temporal medial e suas conexões com o cingulado pré-frontal e amígdala, devido à falta de neurônios específicos ou a uma disfunção neuronal mais geral.

Solvent abuse-related toluene leukoencephalopathy.

The clinical and neuropathological features of a man with solvent vapour-abuse leukoencephalopathy due to toluene is described. The findings suggest that the clinical spectrum of toluene leukencepathalopathy includes dementia with prominent prefrontal dysfunction. In addition, there was evidence of ongoing white matter damage in the form of persistence of PAS-positive macrophages among the demyelinated fibres in the cerebrum and cerebellum, despite the absolute abstinence from toluene for years prior to death.