Disintegration at the Syntax-Semantics Interface in Prodromal Alzheimer's Disease: New Evidence from Complex Sentence Anaphora in Amnestic Mild Cognitive Impairment (aMCI).

Although diverse language deficits have been widely observed in prodromal Alzheimer's disease (AD), the underlying nature of such deficits and their explanation remains opaque. Consequently, both clinical applications and brain-language models are not well-defined. In this paper we report results from two experiments which test language production in a group of individuals with amnestic Mild Cognitive Impairment (aMCI) in contrast to healthy aging and healthy young. The experiments apply factorial designs informed by linguistic analysis to test two forms of complex sentences involving anaphora (relations between pronouns and their antecedents). Results show that aMCI individuals differentiate forms of anaphora depending on sentence structure, with selective impairment of sentences which involve construal with reference to context (anaphoric coreference). We argue that aMCI individuals maintain core structural knowledge while evidencing deficiency in syntax-semantics integration, thus locating the source of the deficit in the language-thought interface of the Language Faculty.

Telemedicine-Based Cognitive Examinations During COVID-19 and Beyond: Perspective of the Massachusetts General Hospital Behavioral Neurology & Neuropsychiatry Group.

Telehealth and telemedicine have encountered explosive growth since the beginning of the COVID-19 pandemic, resulting in increased access to care for patients located far from medical centers and clinics. Subspecialty clinicians in behavioral neurology & neuropsychiatry (BNNP) have implemented the use of telemedicine platforms to perform cognitive examinations that were previously office based. In this perspective article, BNNP clinicians at Massachusetts General Hospital (MGH) describe their experience performing cognitive examinations via telemedicine. The article reviews the goals, prerequisites, advantages, and potential limitations of performing a video- or telephone-based telemedicine cognitive examination. The article shares the approaches used by MGH BNNP clinicians to examine cognitive and behavioral areas, such as orientation, attention and executive functions, language, verbal learning and memory, visual learning and memory, visuospatial function, praxis, and abstract abilities, as well as to survey for neuropsychiatric symptoms and assess activities of daily living. Limitations of telemedicine-based cognitive examinations include limited access to and familiarity with telecommunication technologies on the patient side, limitations of the technology itself on the clinician side, and the limited psychometric validation of virtual assessments. Therefore, an in-person examination with a BNNP clinician or a formal in-person neuropsychological examination with a neuropsychologist may be recommended. Overall, this article emphasizes the use of standardized cognitive and behavioral assessment instruments that are either in the public domain or, if copyrighted, are nonproprietary and do not require a fee to be used by the practicing BNNP clinician.

Unlocking the Hidden Depths: Multi-Modal Integration of Imaging Mass Spectrometry-Based and Molecular Imaging Techniques.

Multimodal imaging (MMI) has emerged as a powerful tool in clinical research, combining different imaging modes to acquire comprehensive information and enabling scientists and surgeons to study tissue identification, localization, metabolic activity, and molecular discovery, thus aiding in disease progression analysis. While multimodal instruments are gaining popularity, challenges such as non-standardized characteristics, custom software, inadequate commercial support, and integration issues with other instruments need to be addressed. The field of multimodal imaging or multiplexed imaging allows for simultaneous signal reproduction from multiple imaging strategies. Intraoperatively, MMI can be integrated into frameless stereotactic surgery. Recent developments in medical imaging modalities such as magnetic resonance imaging (MRI), and Positron Emission Topography (PET) have brought new perspectives to multimodal imaging, enabling early cancer detection, molecular tracking, and real-time progression monitoring. Despite the evidence supporting the role of MMI in surgical decision-making, there is a need for comprehensive studies to validate and perform integration at the intersection of multiple imaging technologies. They were integrating mass spectrometry-based technologies (e.g., imaging mass spectrometry (IMS), imaging mass cytometry (IMC), and Ion mobility mass spectrometry ((IM-IM) with medical imaging modalities, offering promising avenues for molecular discovery and clinical applications. This review emphasizes the potential of multi-omics approaches in tissue mapping using MMI integrated into desorption electrospray ionization (DESI) and matrix-assisted laser desorption ionization (MALDI), allowing for sequential analyses of the same section. By addressing existing knowledge gaps, this review encourages future research endeavors toward multi-omics approaches, providing a roadmap for future research and enhancing the value of MMI in molecular pathology for diagnosis.

Addenbrooke's Cognitive Examination-Third Edition Predicts Neuropsychological Test Performance.

OBJECTIVE: Effective screening tools can help providers with treatment decisions, including when to refer patients for neuropsychological evaluations, which are the gold standard for cognitive assessment of neurodegenerative disease. The authors examined whether performance on the Addenbrooke's Cognitive Examination-Third Edition (ACE-III), a readily available cognitive screening tool for older adults, predicted performance on subsequent neuropsychological evaluations. METHODS: In total, 217 patients referred for neurocognitive concerns completed a neuropsychological evaluation, including the ACE-III. Patients were diagnosed as having normal cognition (NC, N=67), mild neurocognitive disorder (mild NCD, N=105), or major NCD (N=45). Regression analyses were used to determine whether ACE-III subscale scores predicted performance on neuropsychological measures assessing similar constructs. Logistic regression was used to assess whether ACE-III total score and overall neuropsychological test performance predicted diagnosis. Separate analyses compared those with higher and lower educational attainments. ACE-III subscales and total scores were compared by diagnostic group. RESULTS: Across all groups, ACE-III subscale scores predicted within-construct neuropsychological performances with moderate to strong effects (p<0.001) but were less predictive for those with lower educational attainment. ACE-III total score was less sensitive than overall neuropsychological test performance in predicting neurocognitive disorders. ACE-III subscale and total scores distinguished diagnostic groups (NC>mild NCD>major NCD, p<0.001). CONCLUSIONS: ACE-III subscale scores predicted performance on neuropsychological measures assessing similar constructs. However, overall performance on neuropsychological testing was more sensitive than ACE-III total score in predicting neurocognitive disorder diagnosis. Total ACE-III score differed by level of cognitive impairment. Comprehensive neuropsychological testing is recommended for patients who have lower educational status or complex symptom presentations or are younger.

Multimodal Investigation of Neuroinflammation in Aviremic Patients With HIV on Antiretroviral Therapy and HIV Elite Controllers.

BACKGROUND AND OBJECTIVES: The presence of HIV in the CNS has been related to chronic immune activation and cognitive dysfunction. The aim of this work was to investigate (1) the presence of neuroinflammation in aviremic people with HIV (PWH) on therapy and in nontreated aviremic PWH (elite controllers [ECs]) using a translocator protein 18 kDa radioligand; (2) the relationship between neuroinflammation and cognitive function in aviremic PWH; and (3) the relationship between [11C]-PBR28 signal and quantitative MRI (qMRI) measures of brain tissue integrity such as T1 and T2 relaxation times (rts). METHODS: [11C]-PBR28 (standard uptake value ratio, SUVR) images were generated in 36 participants (14 PWH, 6 ECs, and 16 healthy controls) using a statistically defined pseudoreference region. Group comparisons of [11C]-PBR28 SUVR were performed using region of interest-based and voxelwise analyses. The relationship between inflammation, qMRI measures, and cognitive function was studied. RESULTS: In region of interest analyses, ECs exhibited significantly lower [11C]-PBR28 signal in the thalamus, putamen, superior temporal gyrus, prefrontal cortex, and cerebellum compared with the PWH. In voxelwise analyses, differences were observed in the thalamus, precuneus cortex, inferior temporal gyrus, occipital cortex, cerebellum, and white matter (WM). [11C]-PBR28 signal in the WM and superior temporal gyrus was related to processing speed and selective attention in PWH. In a subset of PWH (n = 12), [11C]-PBR28 signal in the thalamus and WM regions was related to a decrease in T2 rt and to an increase in T1 rt suggesting a colocalization of increased glial metabolism, decrease in microstructural integrity, and iron accumulation. DISCUSSION: This study casts a new light onto the role of neuroinflammation and related microstructural alterations of HIV infection in the CNS and shows that ECs suppress neuroinflammation more effectively than PWH on therapy.

Feasibility and Acceptance of Direct-to-Home Tele-neuropsychology Services during the COVID-19 Pandemic.

OBJECTIVE: Neuropsychological assessment via video conferencing has been proposed during the COVID-19 pandemic. Existing literature has demonstrated feasibility and acceptance of neuropsychological measures administered by videoconference, although few studies have examined feasibility and patient acceptance of TNP visits directly to patients' homes (DTH-TNP). METHODS: We modified a previously published patient satisfaction survey for DTH-TNP and developed a clinician feasibility survey to examine experiences during DTH-TNP. RESULTS: Seventy-two patients (age range: preschool-geriatric) evaluated by DTH-TNP for cognitive problems at an academic medical center responded to voluntary surveys between April 20, 2020, and August 19, 2020, and 100% indicated satisfaction. Fifty-nine percent of patients reported limitations (e.g., technological concern) during the appointment. 134 clinician surveys were collected and indicated that clinicians achieved the goal of their appointment in 90% of encounters. CONCLUSIONS: These qualitative data suggest that patients and clinicians found DTH-TNP to be satisfactory during the COVID-19 pandemic, while also recognizing limitations of the practice. These results are limited in that voluntary surveys are subject to bias. They support the growing body of literature suggesting that DTH-TNP provides a valuable service, though additional research to establish reliability and validity is needed.

Language Decline Characterizes Amnestic Mild Cognitive Impairment Independent of Cognitive Decline.

Purpose This research investigated the nature of cognitive decline in prodromal Alzheimer's disease (AD), particularly in mild cognitive impairment, amnestic type (aMCI). We assessed language in aMCI as compared with healthy aging (HA) and healthy young (HY) with new psycholinguistic assessment of complex sentences, and we tested the degree to which deficits on this language measure relate to performance in other general cognitive domains such as memory. Method Sixty-one individuals with aMCI were compared with 24 HA and 10 HY adults on a psycholinguistic measure of complex sentence production (relative clauses). In addition, HA, HY, and a subset of the aMCI participants (n = 22) were also tested on a multidomain cognitive screen, the Addenbrooke's Cognitive Examination-Revised (ACE-R), and on a verbal working memory Brown-Peterson (BP) test. General and generalized linear mixed models were used to test psycholinguistic results and to test whether ACE-R and BP performance predicted performance on the psycholinguistic test similarly in the aMCI and HA groups. Results On the psycholinguistic measure, sentence imitation was significantly deficited in aMCI in comparison with that in HA and HY. Experimental factorial designs revealed that individuals with aMCI had particular difficulty repeating sentences that especially challenged syntax-semantics integration. As expected, the aMCI group also performed significantly below the HY and HA groups on the ACE-R. Neither the ACE-R Memory subtest nor the BP total scores predicted performance on the psycholinguistic task for either the aMCI or the HA group. However, the ACE-R total score significantly predicted psycholinguistic task performance, with increased ACE-R performance predicting increased psycholinguistic task performance only for the HA group, not for the aMCI group. Conclusions Results suggest a selective deterioration in language in aMCI, specifically a weakening of syntax-semantics integration in complex sentence processing, and a general independence of this language deficit and memory decline. Results cohere with previous assessments of the nature of difficulty in complex sentence formation in aMCI. We argue that clinical screening for prodromal AD can be strengthened by supplementary testing of language, as well as memory, and extended evaluation of strength of their relation.

The development and implementation of teleneuropsychology in an academic lifespan neuropsychology center: Lessons learned from the COVID-19 pandemic.

INTRODUCTION: Teleneuropsychology (TNP) became a critical means for providing care during the COVID-19 pandemic and may continue as an option for delivery of neuropsychological services. To understand how patient characteristics impact clinician decisions and service models, this study examines practice patterns within a lifespan outpatient neuropsychology center before, during and post-pandemic. METHODS: Patient volume, demographics, and characteristics were compared across four, 3-month time intervals in 2019-2020. Two baseline intervals when the center was physically open (PO) were compared to one interval when the center was physically closed (PC) (all evaluations were conducted via direct-to-home TNP) and a fourth interval when the center was physically reopened (RO) and evaluations were conducted in one of the three modalities: in-person, virtual only or hybrid (both virtual/in-person). RESULTS: A total of 1,459 total neuropsychological evaluations were conducted with a 64.6% reduction during PC. At RO, the number of evaluations returned to pre-COVID baseline during which in-person (72.4%) evaluations were conducted at a higher rate than hybrid (7.1%) or virtual only (20.4%). Across the lifespan, mean number of appointments to complete evaluations was significantly greater during PC (p< .001) than at other time intervals, and during RO, hybrid evaluations required significantly more appointments (p < .001) than in-person and virtual. The majority of evaluations were conducted with adult patients (71.4%). For adult patients, neurodegenerative/memory disorders received TNP evaluations at a higher rate during PC and RO. Pediatric patients were significantly older during PC (p < .001); neurodevelopmental referrals received more hybrid and virtual evaluations. CONCLUSIONS: Results indicate that patient characteristics, especially age and referral categories, impact the feasibility of TNP. Data from the RO period suggest that in-person evaluations not surprisingly remain the mainstay; however, for adult patients, and especially older adults with neurodegenerative/memory disorders, TNP may provide an important option for delivery of neuropsychological evaluations.

Considering learning disabilities and attention-deficit hyperactivity disorder when assessing for neurodegenerative disease.

PURPOSE OF REVIEW: When evaluating an older adult for a possible neurodegenerative disease, the role of premorbid specific learning disabilities or attention-deficit hyperactivity disorder (ADHD) should be considered. These neurodevelopmental conditions can manifest as lifelong weaknesses and variability in cognitive functions that complicate assessment of cognitive decline. There is also accumulating evidence that certain neurodevelopmental disorders may entail greater risk for specific neurodegenerative disorders. RECENT FINDINGS: We describe clinical cases where diagnosis of neurodegenerative disease was influenced by preexisting neurodevelopmental disorders. We also present a questionnaire to assist with screening for premorbid learning disabilities and ADHD in older adults. SUMMARY: This article offers clinical guidance for practicing neurologists in the identification and assessment of neurodevelopmental disorders in older adult patients, which informs management and treatment. Consideration of lifetime functioning has become increasingly important with research linking neurodevelopmental disabilities to increased risk of specific neurodegenerative diseases.

Diagnostic evaluation and monitoring of patients with posterior cortical atrophy.

Posterior cortical atrophy (PCA) is a progressive neurocognitive syndrome, most commonly associated with the loss of complex visuospatial functions. Diagnosis is challenging, and international consensus classification and nomenclature for PCA subtypes have only recently been reached. Presently, no established treatments exist. Efforts to develop treatments are hampered by the lack of standardized methods to monitor illness progression. Although measures developed from work with Alzheimer's disease and other dementias provide a foundation for diagnosing and monitoring progression, PCA presents unique challenges for clinicians counseling patients and families on clinical status and prognosis, and experts designing clinical trials of interventions. Here, we review issues facing PCA clinical research and care, summarize our approach to diagnosis and monitoring of disease progression, and outline ideas for developing tools for these purposes.

Long-term outcomes and late adverse effects of a prospective study on proton radiotherapy for patients with low-grade glioma.

BACKGROUND: Patients with low-grade gliomas (LGG) can survive years with their illness. Proton radiotherapy (PRT) can reduce off-target dose and decrease the risk of treatment-related morbidity. We examined long-term morbidity following proton therapy in this updated prospective cohort of patients with LGG. METHODS: Twenty patients with LGG were enrolled prospectively and received PRT to 54 Gy(RBE) in 30 fractions. Comprehensive baseline and longitudinal assessments of toxicity, neurocognitive and neuroendocrine function, quality of life, and survival outcomes were performed up to 5 years following treatment. RESULTS: Six patients died (all of disease) and six had progression of disease. Median follow-up was 6.8 years for the 14 patients alive at time of reporting. Median progression-free survival (PFS) was 4.5 years. Of tumors tested for molecular markers, 71% carried the IDH1-R132H mutation and 29% had 1p/19q co-deletion. There was no overall decline in neurocognitive function; however, a subset of five patients with reported cognitive symptoms after radiation therapy had progressively worse function by neurocognitive testing. Six patients developed neuroendocrine deficiencies, five of which received Dmax ≥20 Gy(RBE) to the hypothalamus-pituitary axis (HPA). Most long-term toxicities developed within 2 years after radiation therapy. CONCLUSIONS: The majority of patients with LGG who received proton therapy retained stable cognitive and neuroendocrine function. The IDH1-R132H mutation was present in the majority, while 1p/19q loss was present in a minority. A subset of patients developed neuroendocrine deficiencies and was more common in those with higher dose to the HPA.

Corpus callosum axon diameter relates to cognitive impairment in multiple sclerosis.

OBJECTIVE: To evaluate alterations in apparent axon diameter and axon density obtained by high-gradient diffusion MRI in the corpus callosum of MS patients and the relationship of these advanced diffusion MRI metrics to neurologic disability and cognitive impairment in MS. METHODS: Thirty people with MS (23 relapsing-remitting MS [RRMS], 7 progressive MS [PMS]) and 23 healthy controls were scanned on a human 3-tesla (3T) MRI scanner equipped with 300 mT/m maximum gradient strength using a comprehensive multishell diffusion MRI protocol. Data were fitted to a three-compartment geometric model of white matter to estimate apparent axon diameter and axon density in the midline corpus callosum. Neurologic disability and cognitive function were measured using the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Minimal Assessment of Cognitive Function in MS battery. RESULTS: Apparent axon diameter was significantly larger and axon density reduced in the normal-appearing corpus callosum (NACC) of MS patients compared to healthy controls, with similar trends seen in PMS compared to RRMS. Larger apparent axon diameter in the NACC of MS patients correlated with greater disability as measured by the EDSS (r = 0.555, P = 0.007) and poorer performance on the Symbol Digits Modalities Test (r = -0.593, P = 0.008) and Brief Visuospatial Memory Test-Revised (r = -0.632, P < 0.01), tests of interhemispheric processing speed and new learning and memory, respectively. INTERPRETATION: Apparent axon diameter in the corpus callosum obtained from high-gradient diffusion MRI is a potential imaging biomarker that may be used to understand the development and progression of cognitive impairment in MS.

The Cerebellar Cognitive Affective Syndrome in Ataxia-Telangiectasia.

Ataxia-telangiectasia (AT) is an autosomal recessive, multisystem disease causing cerebellar ataxia, mucocutaneous telangiectasias, immunodeficiency, and malignancies. A pilot study reported cognitive and behavioral manifestations characteristic of the cerebellar cognitive affective / Schmahmann syndrome (CCAS). We set out to test and further define these observations because a more comprehensive understanding of the spectrum of impairments in AT is essential for optimal management. Twenty patients (12 males; 9.86 ± 5.5 years, range 4.3 to 23.2) were grouped by age: AT-I (toddlers and preschoolers, n = 7, 4.3-5.9 years), AT-II (school children, n = 7, 5.9-9.8 years), AT-III (adolescents/young adults, n = 6, 12.6-23.2 years). Standard and experimental tests investigated executive, linguistic, visual-spatial, and affective/social-cognitive domains. Results were compared to standard norms and healthy controls. Cognitive changes in AT-I were limited to mild visual-spatial disorganization. Spatial deficits were greater in AT-II, with low average scores on executive function (auditory working memory), expressive language (vocabulary), academic abilities (math, spelling, reading), social cognition (affect recognition from faces), and emotional/psychological processing. Full Scale IQ scores were low average to borderline impaired. AT-III patients had the greatest level of deficits which were evident particularly in spatial skills, executive function (auditory working memory, sequencing, word/color interference, set-shifting, categorization errors, perseveration), academic achievement, social cognition (affect recognition from faces), and behavioral control. Full Scale IQ scores in this group fell in the impaired range, while language was borderline impaired for comprehension, and low average for expression. Cognitive deficits in AT at a young age are mild and limited to visual-spatial functions. More widespread cognitive difficulties emerge with age and disease progression, impacting executive function, spatial skills, affect, and social cognition. Linguistic processing remains mildly affected. Recognition of the CCAS in children with AT may facilitate therapeutic interventions to improve quality of life.

Executive dysfunction contributes to verbal encoding and retrieval deficits in posterior cortical atrophy.

Posterior Cortical Atrophy (PCA) is a neurodegenerative syndrome that typically presents with predominant visual and spatial impairments. The early diagnostic criteria specify a relative sparing of functioning in other cognitive domains, including executive functions, language, and episodic memory, yet little is known of the cognitive profile of PCA as the disease progresses. Studies of healthy adults and other posterior cortical lesion patients implicate posterior parietal and temporal regions in executive functions of working memory and verbal fluency, both of which may impact episodic memory. Relatively little has been reported about these cognitive functions in PCA, and to our knowledge there has not yet been a study of the impact of such deficits on memory function in PCA. We sought to examine PCA patients' performance on tests of executive function and the associations to verbal episodic memory encoding, storage, and delayed recall. Nineteen individuals with PCA underwent neuropsychological and neuroimaging evaluations as part of a comprehensive clinical assessment. We developed a novel consensus rating method-the Neuropsychological Assessment Rating (NAR) scale-to grade the severity of test performance impairments in selected cognitive domains and subdomains. Hypothesis-driven analyses demonstrated relative deficits in working memory and lexical-semantic retrieval. Preliminary analyses suggested associations between both deficits and atrophy in the left-hemisphere inferior parietal lobule. These executive deficits were also associated with impairments in verbal encoding and delayed recall, but not with recognition discriminability. We conclude that deficits in verbal executive functions impact verbal episodic memory in PCA. Our findings also support theories emphasizing the role of the posterior parietal cortex in supporting executive and lexical-semantic contributions to verbal episodic memory.

Cerebellar cognitive affective syndrome: insights from Joubert syndrome.

BACKGROUND: Joubert syndrome (JS) is a rare, autosomal recessively inherited genetic disorder characterized morphologically by unique developmental malformations of the cerebellum and brainstem (the molar tooth sign), and clinically by impaired motor functions and intellectual disability. Patients with JS often face multiple cognitive challenges, but the neuropsychological profile of this condition has not been well characterized. METHODS: We performed comprehensive neurological and neuropsychological evaluations in three adult brothers with JS, ages 32, 27, and 25 years. RESULTS: They all exhibited impaired motor control, global developmental delay most evident in executive function, affect regulation, and social skill set, and similar patterns of neuropsychiatric symptoms. CONCLUSIONS: These findings provide new insights into the intellectual and neurobehavioral phenotype of JS, which we regard as a developmental form of the cerebellar cognitive affective / Schmahmann syndrome (CCAS). These observations have direct clinical relevance for the diagnosis and care of patients with JS, and they help further the understanding of the multiple manifestations of atypical cerebrocerebellar development.

The cerebellar cognitive affective/Schmahmann syndrome scale.

Cerebellar cognitive affective syndrome (CCAS; Schmahmann's syndrome) is characterized by deficits in executive function, linguistic processing, spatial cognition, and affect regulation. Diagnosis currently relies on detailed neuropsychological testing. The aim of this study was to develop an office or bedside cognitive screen to help identify CCAS in cerebellar patients. Secondary objectives were to evaluate whether available brief tests of mental function detect cognitive impairment in cerebellar patients, whether cognitive performance is different in patients with isolated cerebellar lesions versus complex cerebrocerebellar pathology, and whether there are cognitive deficits that should raise red flags about extra-cerebellar pathology. Comprehensive standard neuropsychological tests, experimental measures and clinical rating scales were administered to 77 patients with cerebellar disease-36 isolated cerebellar degeneration or injury, and 41 complex cerebrocerebellar pathology-and to healthy matched controls. Tests that differentiated patients from controls were used to develop a screening instrument that includes the cardinal elements of CCAS. We validated this new scale in a new cohort of 39 cerebellar patients and 55 healthy controls. We confirm the defining features of CCAS using neuropsychological measures. Deficits in executive function were most pronounced for working memory, mental flexibility, and abstract reasoning. Language deficits included verb for noun generation and phonemic > semantic fluency. Visual spatial function was degraded in performance and interpretation of visual stimuli. Neuropsychiatric features included impairments in attentional control, emotional control, psychosis spectrum disorders and social skill set. From these results, we derived a 10-item scale providing total raw score, cut-offs for each test, and pass/fail criteria that determined 'possible' (one test failed), 'probable' (two tests failed), and 'definite' CCAS (three tests failed). When applied to the exploratory cohort, and administered to the validation cohort, the CCAS/Schmahmann scale identified sensitivity and selectivity, respectively as possible exploratory cohort: 85%/74%, validation cohort: 95%/78%; probable exploratory cohort: 58%/94%, validation cohort: 82%/93%; and definite exploratory cohort: 48%/100%, validation cohort: 46%/100%. In patients in the exploratory cohort, Mini-Mental State Examination and Montreal Cognitive Assessment scores were within normal range. Complex cerebrocerebellar disease patients were impaired on similarities in comparison to isolated cerebellar disease. Inability to recall words from multiple choice occurred only in patients with extra-cerebellar disease. The CCAS/Schmahmann syndrome scale is useful for expedited clinical assessment of CCAS in patients with cerebellar disorders.awx317media15678692096001.

Location of lesion determines motor vs. cognitive consequences in patients with cerebellar stroke.

Cerebellar lesions can cause motor deficits and/or the cerebellar cognitive affective syndrome (CCAS; Schmahmann's syndrome). We used voxel-based lesion-symptom mapping to test the hypothesis that the cerebellar motor syndrome results from anterior lobe damage whereas lesions in the posterolateral cerebellum produce the CCAS. Eighteen patients with isolated cerebellar stroke (13 males, 5 females; 20-66 years old) were evaluated using measures of ataxia and neurocognitive ability. Patients showed a wide range of motor and cognitive performance, from normal to severely impaired; individual deficits varied according to lesion location within the cerebellum. Patients with damage to cerebellar lobules III-VI had worse ataxia scores: as predicted, the cerebellar motor syndrome resulted from lesions involving the anterior cerebellum. Poorer performance on fine motor tasks was associated primarily with strokes affecting the anterior lobe extending into lobule VI, with right-handed finger tapping and peg-placement associated with damage to the right cerebellum, and left-handed finger tapping associated with left cerebellar damage. Patients with the CCAS in the absence of cerebellar motor syndrome had damage to posterior lobe regions, with lesions leading to significantly poorer scores on language (e.g. right Crus I and II extending through IX), spatial (bilateral Crus I, Crus II, and right lobule VIII), and executive function measures (lobules VII-VIII). These data reveal clinically significant functional regions underpinning movement and cognition in the cerebellum, with a broad anterior-posterior distinction. Motor and cognitive outcomes following cerebellar damage appear to reflect the disruption of different cerebro-cerebellar motor and cognitive loops.

Association between adiposity and cognitive function in young men: Hormonal mechanisms.

OBJECTIVE: To determine the association between adiposity, hormones, and cognition in young men with abdominal obesity. METHODS: In this cross-sectional observational study, 53 nondiabetic men with abdominal obesity (mean body mass index, 37.3 kg/m(2) ; age, 22-45 years) and normal intelligence underwent detailed measures of body composition, hormonal profiles, and cognition. Age- and education-adjusted performance in five cognitive domains was examined. RESULTS: Total fat percentage was negatively associated with visuospatial skills (P = 0.002) and visual memory (P = 0.012). Insulin resistance (homeostatic model assessment of insulin resistance) was also negatively associated with these domains (P = 0.05 and trend, P = 0.06, respectively). Total testosterone levels were negatively associated with executive function and verbal learning and memory (P = 0.04 for each), but free testosterone was not. Sex hormone-binding globulin (SHBG) was also inversely associated with performance in these domains (P = 0.015 and trend, P = 0.09, respectively). In a stepwise regression model including percentage fat, homeostatic model assessment of insulin resistance, SHBG, and free testosterone, SHBG was the only variable selected for executive function (P = 0.05) and showed a trend for verbal learning and memory (P = 0.09). CONCLUSIONS: Adiposity and insulin resistance were associated with worse function in visual domains. An unexpected negative association is reported between SHBG and cognitive measures, which seemed to be independent of free testosterone levels.