Neuropsychological Features Research Articles

Lockdown Effects on Healthy Cognitive Aging During the COVID-19 Pandemic: A Longitudinal Study.

The COVID-19 pandemic is a health issue leading older adults to an increased vulnerability to unfavorable outcomes. Indeed, the presence of physical frailty has recently led to higher mortality due to SARS-CoV-2 infection. However, no longitudinal studies have investigated the role of neuropsychogeriatric factors associated with lockdown fatigue in healthy cognitive aging. Eighty-one healthy older adults were evaluated for their neuropsychological characteristics, including physical frailty, before the pandemic (T0). Subsequently, 50 of them agreed to be interviewed and neuropsychologically re-assessed during the lockdown (T1) and immediately after it (T2). Moreover, during another home confinement, they performed a psychological screening (T3) to evaluate possible mood changes and fatigue. According to Fried's frailty criteria, at T0, 63% of the sample was robust, 34.5% pre-frail, and only 2.5% frail. Significantly, these subjects presented a decrease in handgrip strength and walking speed (29.6 and 6.1%, respectively). Results from Principal Component Analyses and multiple regression models highlighted the contribution of “cognitive” and “psychological” factors (i.e., attentive-executive performance and mood deflections) in explaining handgrip strength and gait speed. At T3, lockdown fatigue was explained by higher scores on the Beck Depression Inventory and lower scores on the Trail Making Test part A. Results from a moderated-mediation model showed that the effect of psychomotor speed on lockdown fatigue was mediated by depression, with a moderating effect of gait speed. Our findings highlight the complex interrelationship between cognitive, psychological, and physical factors in the emergence of pandemic fatigue in a carefully selected older population.

Multimodal immersive trail making-virtual reality paradigm to study cognitive-motor interactions

BackgroundNeuropsychological tests of executive function have limited real-world predictive and functional relevance. An emerging solution for this limitation is to adapt the tests for implementation in virtual reality (VR). We thus developed two VR-based versions of the classic Color-Trails Test (CTT), a well-validated pencil-and-paper executive function test assessing sustained (Trails A) and divided (Trails B) attention—one for a large-scale VR system (DOME-CTT) and the other for a portable head-mount display VR system (HMD-CTT). We then evaluated construct validity, test–retest reliability, and age-related discriminant validity of the VR-based versions and explored effects on motor function.MethodsHealthy adults (n = 147) in three age groups (young: n = 50; middle-aged: n = 80; older: n = 17) participated. All participants were administered the original CTT, some completing the DOME-CTT (14 young, 29 middle-aged) and the rest completing the HMD-CTT. Primary outcomes were Trails A and B completion times (tA, tB). Spatiotemporal characteristics of upper-limb reaching movements during VR test performance were reconstructed from motion capture data. Statistics included correlations and repeated measures analysis of variance.ResultsConstruct validity was substantiated by moderate correlations between the’gold standard’ pencil-and-paper CTT and the VR adaptations (DOME-CTT: tA 0.58, tB 0.71; HMD-CTT: tA 0.62, tB 0.69). VR versions showed relatively high test–retest reliability (intraclass correlation; VR: tA 0.60–0.75, tB 0.59–0.89; original: tA 0.75–0.85, tB 0.77–0.80) and discriminant validity (area under the curve; VR: tA 0.70–0.92, tB 0.71–0.92; original: tA 0.73–0.95, tB 0.77–0.95). VR completion times were longer than for the original pencil-and-paper test; completion times were longer with advanced age. Compared with Trails A, Trails B target-to-target VR hand trajectories were characterized by delayed, more erratic acceleration and deceleration, consistent with the greater executive function demands of divided vs. sustained attention; acceleration onset later for older participants.ConclusionsThe present study demonstrates the feasibility and validity of converting a neuropsychological test from two-dimensional pencil-and-paper to three-dimensional VR-based format while preserving core neuropsychological task features. Findings on the spatiotemporal morphology of motor planning/execution during the cognitive tasks may lead to multimodal analysis methods that enrich the ecological validity of VR-based neuropsychological testing, representing a novel paradigm for studying cognitive-motor interactions.

Motor Symptom Lateralization Influences Cortico-Striatal Functional Connectivity in Parkinson's Disease.

Objective: The striatum is unevenly impaired bilaterally in Parkinson's disease (PD). Because the striatum plays a key role in cortico-striatal circuits, we assume that lateralization affects cortico-striatal functional connectivity in PD. The present study sought to evaluate the effect of lateralization on various cortico-striatal circuits through resting-state functional magnetic resonance imaging (fMRI).Methods: Thirty left-onset Parkinson's disease (LPD) patients, 27 right-onset Parkinson's disease (RPD) patients, and 32 normal controls with satisfactory data were recruited. Their demographic, clinical, and neuropsychological information was collected. Resting-state fMRI was performed, and functional connectivity changes of seven subdivisions of the striatum were explored in the two PD groups. In addition, the associations between altered functional connectivity and various clinical and neuropsychological characteristics were analyzed by Pearson's or Spearman's correlation.Results: Directly comparing the LPD and RPD patients demonstrated that the LPD patients had lower FC between the left dorsal rostral putamen and the left orbitofrontal cortex than the RPD patients. In addition, the LPD patients showed aberrant functional connectivity involving several striatal subdivisions in the right hemisphere. The right dorsal caudate, ventral rostral putamen, and superior ventral striatum had decreased functional connectivity with the cerebellum and parietal and occipital lobes relative to the normal control group. The comparison between RPD patients and the controls did not obtain significant difference in functional connectivity. The functional connectivity between the left dorsal rostral putamen and the left orbitofrontal cortex was associated with contralateral motor symptom severity in PD patients.Conclusions: Our findings provide new insights into the distinct characteristics of cortico-striatal circuits in LPD and RPD patients. Lateralization of motor symptoms is associated with lateralized striatal functional connectivity.

Clinical, Neuropsychological, and Neuroimaging Characteristics of Amyloid- positive vs. Amyloid-negative Patients with Clinically Diagnosed Alzheimer's Disease and Amnestic Mild Cognitive Impairment.

A significant proportion of patients with clinically diagnosed Alzheimer's Disease (AD) and an even higher proportion of patients with amnestic mild cognitive impairment (aMCI) do not show evidence of amyloid deposition on Positron Emission Tomography (PET) with amyloid-binding tracers such as 11C-labeled Pittsburgh Compound B (PiB). This study aimed to identify clinical, neuropsychological and neuroimaging factors that might suggest amyloid neuropathology in patients with clinically suspected AD or aMCI. Forty patients with mild to moderate AD and 23 patients with aMCI who were clinically diagnosed in our memory clinic and had PiB PET scans were included. Clinical, neuropsychological, and imaging characteristics, such as Medial Temporal lobe Atrophy (MTA) and White Matter Hyperintensities (WMH) on MRI and metabolic pattern on 18F-labeled fluorodeoxyglucose (FDG) PET, were compared between patients with PiB positive and negative PET results for AD, aMCI, and all subjects combined, respectively. Compared with PiB positive patients, PiB negative patients had a higher prevalence of hypertension history, better performance on the Mini-Mental State Examination, the Rey Auditory Verbal Learning Test, and the Judgement of Line Orientation, lower score of MTA, and were less likely to have temporoparietal-predominant hypometabolism on FDG PET. Affective symptoms were less common in PiB negative patients diagnosed with AD, and the Animal Fluency Test score was higher in PiB negative patients diagnosed with aMCI. In patients with clinically diagnosed AD or aMCI, absence of a history of hypertension, deficits in verbal learning and memory, visuospatial function, semantic verbal fluency, presence of affective symptoms, MTA on MRI, and temporoparietal hypometabolism on FDG PET suggested amyloid deposition in the brain.

Comparing the Clinical and Neuropsychological Characteristics of Parkinson’s Disease With and Without Freezing of Gait

IntroductionFreezing of gait (FOG) is one of the most common walking problems in Parkinson’s disease (PD). Impaired cognitive function is believed to play an important role in developing and aggravating FOG in PD. But some evidence suggests that motor function discrepancy may affect testing results. Therefore, we think it is necessary for PD-FOG(+) and PD-FOG(−) patients to complete neuropsychological tests under similar motor conditions.MethodsThis study recruited 44 idiopathic PD patients [PD-FOG(+) n = 22, PD-FOG(−) n = 22] and 20 age-matched healthy controls (HC). PD-FOG(+) and PD-FOG(−) patients were matched for age, year of education, and Hoehn and Yahr score (H&Y). All participants underwent a comprehensive battery of neuropsychological assessment, and demographical and clinical information was also collected.ResultsPD patients showed poorer cognitive function, higher risks of depression and anxiety, and more neuropsychiatric symptoms compared with HC. When controlling for age, years of education, and H&Y, there were no statistical differences in cognitive function between PD-FOG(+) and PD-FOG(−) patients. But PD-FOG(+) patients had worse motor and non-motor symptoms than PD-FOG(−) patients. PD patients whose motor symptoms initiated with rigidity and initiated unilaterally were more likely to experience FOG.ConclusionTraditional neuropsychological testing may not be sensitive enough to detect cognitive impairment in PD. Motor symptoms initiated with rigidity and initiated unilaterally might be an important predictor of FOG.

EEG-fMRI Signal Coupling Is Modulated in Subjects With Mild Cognitive Impairment and Amyloid Deposition.

Cognitive impairment indicates disturbed brain physiology which can be due to various mechanisms including Alzheimer's pathology. Combined functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) recordings (EEG-fMRI) can assess the interplay between complementary measures of brain activity and EEG changes to be localized to specific brain regions. We used a two-step approach, where we first examined changes related to a syndrome of mild cognitive impairment irrespective of pathology and then studied the specific impact of amyloid pathology. After detailed clinical and neuropsychological characterization as well as a positron emission tomography (PET) scans with the tracer 11-[C]-Pittsburgh Compound B to estimate cerebral amyloid deposition, 14 subjects with mild cognitive impairment (MCI) (mean age 75.6 SD: 8.9) according to standard criteria and 21 cognitively healthy controls (HCS) (mean age 71.8 SD: 4.2) were assessed with EEG-fMRI. Thalamo-cortical alpha-fMRI signal coupling was only observed in HCS. Additional EEG-fMRI signal coupling differences between HCS and MCI were observed in parts of the default mode network, salience network, fronto-parietal network, and thalamus. Individuals with significant cerebral amyloid deposition (amyloid-positive MCI and HCS combined compared to amyloid-negative HCS) displayed abnormal EEG-fMRI signal coupling in visual, fronto-parietal regions but also in the parahippocampus, brain stem, and cerebellum. This finding was paralleled by stronger absolute fMRI signal in the parahippocampus and weaker absolute fMRI signal in the inferior frontal gyrus in amyloid-positive subjects. We conclude that the thalamocortical coupling in the alpha band in HCS more closely reflects previous findings observed in younger adults, while in MCI there is a clearly aberrant coupling in several networks dominated by an anticorrelation in the posterior cingulate cortex. While these findings may broadly indicate physiological changes in MCI, amyloid pathology was specifically associated with abnormal fMRI signal responses and disrupted coupling between brain oscillations and fMRI signal responses, which especially involve core regions of memory: the hippocampus, para-hippocampus, and lateral prefrontal cortex.

Neuropsychological and neuroimaging characteristics of classical superficial siderosis.

To define the neuropsychological and neuroimaging characteristics of classicalinfratentorial superficial siderosis (iSS), a rare but disabling disorder defined by hemosiderin deposition affecting the superficial layers of the cerebellum, brainstem and spinal cord, usually associated with a slowly progressive neurological syndrome of deafness, ataxia and myelopathy. We present the detailed neuropsychological and neuroimaging findings in 16 patients with iSS (mean age 57years; 6 female). Cognitive impairment was present in 8/16 (50%) of patients: executive dysfunction was the most prevalent (44%), followed by impairment of visual recognition memory (27%); other cognitive domains were largely spared. Disease symptom duration was significantly correlated with the number of cognitive domains impaired (r = 0.59, p = 0.011). Mood disorders were also common (anxiety 62%, depression 38%, both 69%) but not associated with disease symptom duration. MRI findings revealed siderosis was not only in infratentorial brain regions, but also in characteristic widespread symmetrical supratentorial brain regions, independent of disease duration and degree of cognitive impairment. The presence of small vessel disease markers was very low and did not account for the cognitive impairment observed. Neuropsychological disturbances are common in iSS and need to be routinely investigated. The lack of association between the anatomical extent of hemosiderin and cognitive impairment or disease duration suggests that hemosiderin itself is not directly neurotoxic. Additional biomarkers of iSS disease severity and progression are needed for future research and clinical trials.

Subclinical manic symptoms predict social cognitive impairment mediated by deficits in executive functioning in older adults with mood disorders

<h3>Introduction</h3> Bipolar disorder can impair executive functioning and social cognition which refers to the cognitive processes involved in understanding social cues (this includes theory of mind). However, little is known about the degree to which subclinical manic symptoms can impact social cognition in older adults and the role of executive functioning in this interaction. This cross-sectional study examined if transdiagnostic subclinical manic symptoms in older adults with mood disorders were related to impaired social cognition and if this relationship was mediated by executive functioning. <h3>Methods</h3> Ninety-five mood disorder patients (43 patients with bipolar disorder, 50 with major depressive disorder, 2 with schizoaffective disorder) ages 55 and above completed a battery of neuropsychological tests, mood and anxiety rating scales, clinical rating scales, functional and medical assessments. Total scores from the Mind in the Eyes task were used to assess social cognition. Executive functioning was assessed using the total correct scores from the Wisconsin Card Sorting Task (WCST). The Young Mania Rating Scale (YMRS), the Generalized Anxiety Disorder 7-item (GAD-7) scale and the Montgomery-Asberg Depression Rating Scale (MADRS) were used to assess mood and anxiety symptoms. <h3>Results</h3> All participants had subclinical manic symptoms based on the YMRS scores independent of their diagnosis. We used linear regressions to test mediation following the Baron and Kenny (1986) method. We found that greater subclinical manic symptoms (YMRS) were related to reduced executive functioning (path a, <i>p</i>=.043), and lower social cognitive functioning (Mind in the Eyes task), when controlling for depression and anxiety symptoms (path c, <i>p</i> = .002). The association between manic symptoms and social cognition was fully mediated by performance on an executive functioning task (the Wisconsin Card Sorting Task total correct scores, path b, <i>p</i>=.010, path c' <i>p</i>= .375). Mood diagnosis, depression and anxiety symptoms were not significantly related to performance on social cognitive or executive functioning tasks. <h3>Conclusions</h3> Executive functioning could explain social cognitive impairment related to subclinical manic symptoms. Our findings shed some light into the neuropsychological features of subclinical manic symptoms in older adults. <h3>Funding</h3> The Rogers Family Foundation

The syndrome of transient epileptic amnesia: a combined series of 115 cases and literature review.

The term transient epileptic amnesia was coined in 1990 to describe a form of epilepsy causing predominantly amnestic seizures which could be confused with episodes of Transient Global Amnesia. Subsequent descriptions have highlighted its association with ‘atypical’ forms of memory disturbance including accelerated long-term forgetting, disproportionate autobiographical amnesia and topographical amnesia. However, this highly treatment-responsive condition remains under-recognized and undertreated. We describe the clinical and neuropsychological features in 65 consecutive cases of transient epileptic amnesia referred to our study, comparing these to our previous cohort of 50 patients and to those reported in 102 literature cases described since our 2008 review. Findings in our two cohorts are substantially consistent: The onset of transient epileptic amnesia occurs at an average age of 62 years, giving rise to amnestic episodes at a frequency of around 1/month, typically lasting 15–30 min and often occurring on waking. Amnesia is the only manifestation of epilepsy in 24% of patients; olfactory hallucinations occur in 43%, motor automatisms in 41%, brief unresponsiveness in 39%. The majority of patients describe at least one of the atypical forms of memory disturbance mentioned above; easily provoked tearfulness is a common accompanying feature. There is a male predominance (85:30). Epileptiform changes were present in 35% of cases, while suspected causative magnetic resonance imaging abnormalities were detected in only 5%. Seizures ceased with anticonvulsant treatment in 93% of cases. Some clinical features were detected more commonly in the second series than the first, probably as a result of heightened awareness. Neuropsychological testing and comparison to two age and IQ-matched control groups (n = 24 and 22) revealed consistent findings across the two cohorts, namely elevated mean IQ, preserved executive function, mild impairment at the group level on standard measures of memory, with additional evidence for accelerated long-term forgetting and autobiographical amnesia, particularly affecting episodic recollection. Review of the literature cases revealed broadly consistent features except that topographical amnesia, olfactory hallucinations and emotionality have been reported rarely to date by other researchers. We conclude that transient epileptic amnesia is a distinctive syndrome of late-onset limbic epilepsy of unknown cause, typically occurring in late middle age. It is an important, treatable cause of memory loss in older people, often mistaken for dementia, cerebrovascular disease and functional amnesia. Its aetiology, the monthly occurrence of seizures in some patients and the mechanisms and interrelationships of the interictal features—amnestic and affective—all warrant further study.

Evaluating cognitive profiles of patients undergoing clinical amyloid-PET imaging.

Episodic memory impairment and brain amyloid-beta are two of the main hallmarks of Alzheimer’s Disease. In the clinical setting, these are often evaluated through neuropsychological testing and amyloid PET imaging, respectively. The use of amyloid PET in clinical practice is only indicated in patients with substantial diagnostic uncertainty due to atypical clinical presentation, multiple comorbidities and/or early age of onset. The relationship between amyloid-beta and cognition has been previously investigated, but no study has examined how neuropsychological features relate to the presence of amyloid pathology in the clinical population that meets the appropriate use criteria for amyloid PET imaging. In this study, we evaluated a clinical cohort of patients (n = 107) who presented at the Imperial Memory Clinic and were referred for clinical amyloid PET and neuropsychological assessment as part of their diagnostic workup. We compared the cognitive performance of amyloid-positive patients (Aβ-pos, n = 47) with that of stable amyloid-negative (stableAβ-neg, n = 26) and progressive amyloid-negative (progAβ-neg, n = 34) patients. The amyloid-positive group performed significantly worse than both amyloid-negative groups in the visuospatial and working memory domains. Episodic memory performance, however, effectively differentiated the amyloid-positive group from the stable but not the progressive amyloid-negative group. On affective questionnaires, the stable amyloid-negative group reported significantly higher levels of depression than the amyloid-positive group. In our clinical cohort, visuospatial dysfunction and working memory impairment were better indicators of amyloid positivity than episodic memory dysfunction. These findings highlight the limited value of isolated cognitive scores in patients with atypical clinical presentation, comorbidities and/or early age of onset.

Prevalence and Clinical Features of FOG in Chinese PD Patients, a Multicenter and Cross-Sectional Clinical Study.

Objectives: Freezing of gait (FOG) is generally considered as an independent symptom of Parkinson's disease (PD) with a complex pathophysiology. There is a wide range of associated clinical features of FOG reported from different studies without consistent conclusion. Thus, a multicenter, cross-sectional study was designed to investigate the prevalence and clinical features of FOG together with its unique contribution quality of life in Chinese PD patients.Methods: Eight hundred and thirty eight PD patients were consecutively recruited into this study from 12 hospital centers in six provinces in China. Clinical information, including motor and neuropsychological features as well as pharmacological details, was collected.Results: Of 827 PD patients, 245 (29.63%) reported FOG. The prevalence of FOG was strongly correlated with modified H-Y stages and symptomatic duration (p < 0.01). 84.90% freezers experienced FOG during turning and 88.98% experienced when initiating the first step. Compared with non-freezers, freezers reported longer disease duration (7.73 ± 5.44 vs. 4.69 ± 3.94, p < 0.000), higher frequent PIGD phenotype (61.22 vs. 35.91%, p < 0.000), higher scores of UPDRS III (32.85 ± 15.47 vs. 22.38 ± 12.89, p < 0.000), HAMA (10.99 ± 7.41 vs. 7.59 ± 6.47, p < 0.000), HAMD (15.29 ± 10.29 vs. 10.58 ± 8.97, p < 0.000) and lower MMSE score (25.12 ± 5.27 vs. 26.63 ± 3.97, p < 0.000), and higher daily levodopa dosage (432.65 ± 264.31 vs. 319.19 ± 229.15, p < 0.000) with less frequent initial use of dopaminergic agonist (8.57 vs. 14.78%, p < 0.05). Using binary logistic regression, the associated factors of FOG might be non-tremor dominant onset (OR = 3.817, p < 0.000), the presence of anxiety (OR = 2.048, p < 0.000) and imbalance (OR = 4.320, p = 0.012). Freezers had poorer quality of life than non-freezers and FOG impacted PDQ-8 independently.Conclusion: Nearly one third of the PD patients experienced FOG. Its frequency increased with PD progression and FOG reduced independently the quality of life. Non-tremor dominant, disease progression, and anxiety were risk factors of FOG.

Intervención no farmacológica sobre el control inhibitorio en adolescentes con trastorno por déficit de atención/hiperactividad

Una de las principales características neuropsicológicas del Trastorno por Déficit de Atención/Hiperactividad (TDAH) son las fallas en las funciones ejecutivas, principalmente en el Control Inhibitorio (CI), la cual es importante para la detención de una respuesta en marcha, permite una demora en la decisión para responder y protege este período de tiempo. Derivado de estas fallas, la población adolescente con TDAH es la más susceptible a presentar conductas como el abuso de sustancias, la conducta sexual de riesgo y la presencia de comorbilidades. El objetivo del presente trabajo fue revisar la literatura de los últimos 10 años acerca de las intervenciones no farmacológicas sobre el CI en adolescentes con TDAH. Se realizó una búsqueda electrónica en las bases de datos: Scopus, PubMed y Web of Science, combinando las siguientes palabras clave: “intervention”, “inhibitory control”, “adolescents”, “teenagers” y “ADHD”. Se seleccionaron artículos publicados desde el 2010 hasta el 2020. La estimulación magnética transcraneal es la intervención no farmacológica más reportada para mejorar el CI en adolescentes con TDAH, seguida del ejercicio físico y el neurofeedback. La literatura es escasa al abordar el tema, por lo que resulta de importancia generar futuras líneas de investigación sobre el tratamiento de las funciones ejecutivas en adolescentes con TDAH.

Information-theoretic characterization of eye-tracking signals with relation to cognitive tasks

Eye tracking is being increasingly used as a more powerful diagnosis instrument when compared with traditional pen-and-paper tests in psychopedagogy and psychology. This technology may significantly improve neurocognitive assessments in gathering indirect latent information about the subjects’ performance. However, the meaning and implications of these data are far from being fully understood. In this work, we present a comprehensive study of eye tracking time series in terms of statistical complexity measures. We registered the eye tracking movements of several subjects solving the two parts of the commonly applied Trail Making Test (TMT-A and TMT-B) and studied their Shannon entropy, disequilibrium, statistical complexity, and Fisher information with respect to three different probability distributions. The results show that these quantifiers reveal information about different features of the gaze depending on the distribution considered. As a meaningful result, we found that Fisher information in the position distribution reflects the difficulties encountered by the subject when solving the task. Such a characterization may be of interest to understand the underlying cognitive tasks performed by the subjects, and, additionally, it can serve as a source of valuable parameters to quantitatively assess how and why the subjects budget their attention, providing psychologists and psychopedagogues with more refined neuropsychological evaluation features and tools.

Investigating ZFYVE26 mutations in a Taiwanese cohort with hereditary spastic paraplegia

Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited neurodegenerative disorders characterized by slowly progressive lower limbs spasticity and weakness. HSP type 15 (SPG15) is an autosomal recessive subtype caused by ZFYVE26 mutations. The aim of this study was to investigate the frequency and clinical and genetic features of ZFYVE26 mutations in a Taiwanese HSP cohort. Mutational analysis of the coding regions of ZFYVE26 was performed by targeted resequencing in the 195 unrelated Taiwanese patients with HSP. All of the patients were of Han Chinese ethnicity. Clinical, neuropsychological, electrophysiological evaluations and imaging studies were collected. Among the 195 patients, only one SPG15 patient was identified. The patient had a novel recessive ZFYVE26 frameshift truncating mutation, p.R1806Gfs∗36 (c.5415delC), and presented with insidious onset spastic weakness of lower-extremities and cognitive impairment. Neuropsychological assessment revealed deficits in executive function, visual naming, category verbal fluency, and manual dexterity. Brain MRI showed thin corpus callosum and the "ears of lynx" sign. SPG15 accounts for approximately 0.5% (1/195) of the Taiwanese HSP cohort. This study identified the first Taiwanese SPG15 case and delineated the clinical, genetic, neuropsychological, and neuroimaging features. These findings expand the mutational spectrum of ZFYVE26 and also broaden the knowledge of clinical and neuropsychological characteristics of SPG15.

Multiple Subtypes of Alzheimer's Disease Base on Brain Atrophy Pattern.

Alzheimer’s disease (AD) is a disease of a heterogeneous nature, which can be disentangled by exploring the characteristics of each AD subtype in the brain structure, neuropathology, and cognition. In this study, a total of 192 AD and 228 cognitively normal (CN) subjects were obtained from the Alzheimer’s disease Neuroimaging Initiative database. Based on the cortical thickness patterns, the mixture of experts method (MOE) was applied to the implicit model spectrum of transforms lined with each AD subtype, then their neuropsychological and neuropathological characteristics were analyzed. Furthermore, the piecewise linear classifiers composed of each AD subtype and CN were resolved, and each subtype was comprehensively explained. The following four distinct AD subtypes were discovered: bilateral parietal, frontal, and temporal atrophy AD subtype (occipital sparing AD subtype (OSAD), 29.2%), left temporal dominant atrophy AD subtype (LTAD, 22.4%), minimal atrophy AD subtype (MAD, 16.1%), and diffuse atrophy AD subtype (DAD, 32.3%). These four subtypes display their own characteristics in atrophy pattern, cognition, and neuropathology. Compared with the previous studies, our study found that some AD subjects showed obvious asymmetrical atrophy in left lateral temporal-parietal cortex, OSAD presented the worst cerebrospinal fluid levels, and MAD had the highest proportions of APOE ε4 and APOE ε2. The subtype characteristics were further revealed from the aspect of the model, making it easier for clinicians to understand. The results offer an effective support for individual diagnosis and prognosis.

Temporal lobe dysfunction in late-onset epilepsy of unknown origin

ObjectiveEpilepsy with onset in the adulthood is an increasing health problem, due to the progressive aging of the worldwide population. Whether the causes remain undetermined, the disease is defined as Late-Onset Epilepsy of Unknown origin (LOEU). The aim of this study was to evaluate the semiological, electroencephalographic, metabolic, and neuropsychological features of LOEU. MethodsWe selected patients with late-onset epilepsy (LOE) (≥55 years), whose causes of the disease have been excluded with a deep clinical-instrumental characterization, including brain MRI, EEG, 18F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET), and neuropsychological assessment. ResultsTwenty-three LOEU cases were retrospectively recruited. Half presented focal-onset seizures (FOS), the others focal to bilateral tonic-clonic seizures (FBTCS). All demonstrated a mild phenotype, with no recurrence of seizures on single antiseizure treatment at prolonged follow-up. Brain MRI scans were normal in 12 patients (52.3%) and showed nonspecific gliosis or mild atrophy in ten (43.5%); hippocampal sclerosis (HS) was observed in one. In 17/23 (73.9%), the EEG showed slow and/or epileptiform activity of the temporal areas. Brain FDG-PET revealed temporal lobe hypometabolism, mostly ipsilateral to EEG abnormal activity, or multifocal temporal and extra-temporal (cortical, subcortical and subtentorial) clusters of hypometabolism. The neuropsychological analysis demonstrated three different profiles: normal (43.5%), with focal deficits (39.1%) or mild multidomain impairment (17.4%). SignificanceLate-Onset Epilepsy of Unknown origin can present as FOS or FBTCS, both with good prognosis. The application of metabolic imaging and neurophysiology techniques in these patients points to the dysfunction of the temporal structures, whose role in the pathogenetic process of the disease remains to be clarified.

Influence of cardiovascular risk factors on pre-mild cognitive decline at middle and old age

Much attention is currently paid to non-dementia cognitive impairment, such as mild cognitive impairment and pre-mild cognitive decline (PMCD), since their timely detection and optimal correction increase the possibility of preventing dementia.Objective: to analyze the neuropsychological characteristics of patients with PMCD depending on the presence or absence of cardiovascular risk factors (CVRFs): hypertension, cardiac disorders (ischemic heart disease, intracardiac conduction disturbance), and prior stroke and myocardial infarction, as well as diabetes mellitus.Patients and methods. Examinations were made in 182 patients (132 women, 50 men; mean age, 59.32±5.41 years) with PMCD and CVFRs, 101 patients (77 women, 24 men; mean age, 59.45±7.04 years) with PMCD without CVRFs, and 77 control persons (55 women, 22 men; mean age, 60.55±5.65 years). All underwent general clinical, neurological, and clinical psychological studies using rating scales and tests.Results and discussion. The patients with PMCD and CVRFs had lower scores on all neuropsychological tests than the control group and on most tests than the patients with PMCD without CVRFs. In addition to some deterioration in memory indicators, the patients with CVRFs performed worse executive function tests. Cluster analysis showed that in the patients with PMCD, the severity of cognitive decline was considerably affected by hypertension, cardiac disorders, and diabetes mellitus; among them, hypertension was of the most significance.Conclusion. The association of cognitive decline with the burden of CVRFs indicates their important role in the deterioration of cognitive functions in PMCD.

Association between ApoE ε4 Carrier Status and Cardiovascular Risk Factors on Mild Cognitive Impairment among Mexican Older Adults.

Mild cognitive impairment (MCI) (amnestic or non-amnestic) has different clinical and neuropsychological characteristics, and its evolution is heterogeneous. Cardiovascular risk factors (CVRF), such as hypertension, diabetes, or dyslipidemia, and the presence of the Apolipoprotein E ε4 (ApoE ε4) polymorphism have been associated with an increased risk of developing Alzheimer’s disease (AD) and other dementias but the relationship is inconsistent worldwide. We aimed to establish the association between the ApoE ε4 carrier status and CVRF on MCI subtypes (amnestic and non-amnestic) in Mexican older adults. Cross-sectional study including 137 older adults (n = 63 with normal cognition (NC), n = 24 with amnesic, and n = 50 with non-amnesic MCI). Multinomial logistic regression models were performed in order to determine the association between ApoE ε4 polymorphism carrier and CVRF on amnestic and non-amnestic-MCI. ApoE ε4 carrier status was present in 28.8% participants. The models showed that ApoE ε4 carrier status was not associated neither aMCI nor naMCI condition. The interaction term ApoE ε4 × CVRF was not statistically significant for both types of MCI. However, CVRF were associated with both types of MCI and the association remained statistically significant after adjustment by sex, age, and education level. The carrier status of the ApoE genotype does not contribute to this risk.

Are Socio-Affective Impairments in Ataxia Related to Language and Processing Speed Deficits?

Over the last decade a number of studies have demonstrated the implication of the cerebellum in cognition, including verbal memory, executive function, and language. Social cognition abilities like emotion attribution and theory of mind are essential in social interaction and rely on verbal abilities and executive functions. Involvement in social cognition has been explored in the most common forms of Spinocerebellar Ataxia (SCA), but several aspects remain unclear. The present study tested whether socio-affective impairments are observed in SCA patients by using different tasks and to determine whether these impairments were associated with reduced verbal processing and/or processing speed. 13 patients (SCA1, n=1; SC2, n=5; SCA3, n=7) were matched with 13 controls for gender, age and education. Verbal and non-verbal theory of mind abilities were tested (validated French versions of an attribution of intention test, faux-pas test), and emotion attribution. Language efficacy was explored in a word fluency test and processing speed in two non-motor tasks. Results revealed no difference between SCA2 and SCA3 patients in neither socio-affective nor cognitive test. Performance on all tests was on contrary significantly reduced in the SCA patient group compared to controls. SCA patients’ performance was positively correlated between the three social cognition tests, indicating a somewhat generalized impairment. Their performance rate in each of three social cognition tests was further correlated with processing speed but not with word fluency. In the verbal theory of mind task they displayed however comprehension deficits of the faux-pas and of general control questions. Taken together the data suggest that processing speed and comprehension difficulties might account, partly at least, for socio-affective and cognitive deficits in both genotypes. This conclusion was modulated by the observation that the neuropsychological features did not correspond well with age of illness diagnosis and illness duration, indicating that there is a degree of heterogeneity in the cognitive profiles and social cognitive impairments in SCA patients.

A Review of Brain Atrophy Subtypes Definition and Analysis for Alzheimer’s Disease Heterogeneity Studies

Alzheimer's disease (AD) is a heterogeneous disease with different subtypes. Studying AD subtypes from brain structure, neuropathology, and cognition are of great importance for AD heterogeneity research. Starting from the study of constructing AD subtypes based on the features of T1-weighted structural magnetic resonance imaging, this paper introduces the major connections between the subtype definition and analysis strategies, including brain region-based subtype definition, and their demographic, neuropathological, and neuropsychological characteristics. The advantages and existing problems are analyzed, and reasonable improvement schemes are prospected. Overall, this review offers a more comprehensive view in the field of atrophy subtype in AD, along with their advantages, challenges, and future prospects, and provide a basis for improving individualized AD diagnosis.