Temporal Atrophy Research Articles

Association between homocysteine levels and cognitive profile in Alzheimer’s Disease

BackgroundGrowing evidence suggests that hyperhomocysteinemia (HHcy) constitutes a risk factor for Alzheimer’s Disease (AD). The impact of HHcy on cognitive functions has mainly been investigated using screening neuropsychological tests that provide general, unspecific measures of cognitive level. Since an association between HHcy and temporo-mesial atrophy has been documented, we predicted that a fine-grained analysis of neuropsychological performance should show stronger Hcy effects on memory scores than on other cognitive scores. ObjectiveTo determine the influence of Hcy level on cognitive profile evaluated with specific, sensitive neuropsychological tests in a wide AD cohort. Methods323 patients with AD were enrolled in a cross-sectional study and underwent a neuropsychological examination exploring several cognitive domains (memory, language, visuoperception, visuospatial abilities, executive function, constructional praxis, ideomotor praxis). The effects of Hcy levels and other risk factors (including cholesterol, smoking habits, triglycerides, apoEε4 allele) were analysed. ResultsGeneralized Linear Model detected a significant drop in performance with increasing Hcy in 6/19 measures of cognitive functions, namely, in memory performance tasks as well as in Luria’s motor planning test, with effect sizes ranging 1.4%–2.8% (Eta-squared), partialling out effects of other predictors. ConclusionsHHcy was associated with poor performance in short and long-term spatial and verbal memory more than with other cognitive dysfunctions. These results support the hypothesis that medial temporal networks might be vulnerable to HHcy, consistently with data from neuroimaging studies suggesting a link in AD between temporal atrophy and HHcy; the effect on Luria’s motor planning task suggests further involvement of frontal structures.

Specificity of Entorhinal Atrophy MRI Scale in Predicting Alzheimer's Disease Conversion.

We compared entorhinal cortex atrophy (ERICA) score vs. medial temporal atrophy (MTA) score's ability to predict conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD) using magnetic resonance imaging (MRI). We hypothesized that ERICA would show higher specificity. Data from 61 aMCI patients were analyzed. Positive ERICA was associated with AD conversion with a sensitivity of 56% (95% CI: 30-80%) and a specificity of 78% (63-89%) vs. 69% (41-89%) SE and 60% (44-74%) SP for the MTA. Results suggest that ERICA is superior to MTA in predicting conversion from aMCI to AD in a small sample of participants.

Frontotemporal right predominant hypometabolism in bvFTD is not frequent and associated with more severe temporal atrophy

Prosopagnosia, memory deficits and behavioural changes has recently proposed as the core symptoms of a further variant of frontotemporal dementia, associated with right temporal atrophy or hypometabolism and named right temporal variant (rtvFTD). Aim of the study was to evaluate frequency and clinical characteristics of patients with prevalent fronto and/or temporal right atrophy/hypometabolism.

How to make a diagnosis in people with late-onset behavioral change

Behavioral Variant Frontotemporal Dementia is a neurodegenerative brain disorder associated with frontal, insular, and temporal lobar atrophy, characterized during its earliest stages by pervasive changes in personality and behavior, typically reported by the patient's caregivers. Behavioral symptoms include loss of empathy, disinhibition, compulsive behavior, and a shift towards impulsive and socially inappropriate behavior, most of which generally precede the onset of cognitive deficits. Whilst patients with bvFTD usually exhibit deficits on executive functions tests, other cognitive functions, such as visuospatial abilities and praxis, remain relatively well preserved early in the disease (although a subset of patients do present with significant episodic memory disturbance). In the absence of a biological marker, clinical diagnosis of bvFTD depends on the detection of these core neuropsychiatric features, making it difficult for practicing physicians to diagnose early bvFTD. Several factors make diagnosis of a possible behavioral variant of frontotemporal dementia (bvFTD) particularly challenging, especially the overlap of certain symptomatic dimensions such as apathy, disinhibition, depression, anhedonia, stereotyped behavior, and psychosis between bvFTD and several psychiatric disorders that appear in late adulthood. I will discuss the most frequent psychiatric conditions that can simulate early bvFTD symptoms, including late onset bipolar disorder, late onset schizophrenia-like psychosis, late onset depression, and attention deficit hyperactivity disorder in middle and older age.

Tackling clinical heterogeneity across the amyotrophic lateral sclerosis–frontotemporal dementia spectrum using a transdiagnostic approach

The disease syndromes of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) display considerable clinical, genetic and pathological overlap, yet mounting evidence indicates substantial differences in progression and survival. To date, there has been limited examination of how profiles of brain atrophy might differ between clinical phenotypes. Here, we address this longstanding gap in the literature by assessing cortical and subcortical grey and white matter volumes on structural MRI in a large cohort of 209 participants. Cognitive and behavioural changes were assessed using the Addenbrooke’s Cognitive Examination and the Cambridge Behavioural Inventory. Relative to 58 controls, behavioural variant FTD (n = 58) and ALS–FTD (n = 41) patients displayed extensive atrophy of frontoinsular, cingulate, temporal and motor cortices, with marked subcortical atrophy targeting the hippocampus, amygdala, thalamus and striatum, with atrophy further extended to the brainstem, pons and cerebellum in the latter group. At the other end of the spectrum, pure-ALS patients (n = 52) displayed considerable frontoparietal atrophy, including right insular and motor cortices and pons and brainstem regions. Subcortical regions included the bilateral pallidum and putamen, but to a lesser degree than in the ALS–FTD and behavioural variant FTD groups. Across the spectrum the most affected region in all three groups was the insula, and specifically the anterior part (76–90% lower than controls). Direct comparison of the patient groups revealed disproportionate temporal atrophy and widespread subcortical involvement in ALS–FTD relative to pure-ALS. In contrast, pure-ALS displayed significantly greater parietal atrophy. Both behavioural variant FTD and ALS–FTD were characterized by volume decrease in the frontal lobes relative to pure-ALS. The motor cortex and insula emerged as differentiating structures between clinical syndromes, with bilateral motor cortex atrophy more pronounced in ALS–FTD compared with pure-ALS, and greater left motor cortex and insula atrophy relative to behavioural variant FTD. Taking a transdiagnostic approach, we found significant associations between abnormal behaviour and volume loss in a predominantly frontoinsular network involving the amygdala, striatum and thalamus. Our findings demonstrate the presence of distinct atrophy profiles across the ALS–FTD spectrum, with key structures including the motor cortex and insula. Notably, our results point to subcortical involvement in the origin of behavioural disturbances, potentially accounting for the marked phenotypic variability typically observed across the spectrum.

Distinct amyloid and tau PET signatures are associated with diverging clinical and imaging trajectories in patients with amnestic syndrome of the hippocampal type

We aimed to investigate the amyloid and tau PET imaging signatures of patients with amnestic syndrome of the hippocampal type (ASHT) and study their clinical and imaging progression according to their initial PET imaging status. Thirty-six patients with a progressive ASHT and 30 controls underwent a complete neuropsychological assessment, 3 T brain MRI, [11C]-PiB and [18F]-Flortaucipir PET imaging. Subjects were clinically followed-up annually over 2 years, with a second 3 T MRI (n = 27 ASHT patients, n = 28 controls) and tau-PET (n = 20 ASHT patients) at the last visit. At baseline, in accordance with the recent biological definition of Alzheimer’s disease (AD), the AD PET signature was defined as the combination of (i) positive cortical amyloid load, and (ii) increased tau tracer binding in the entorhinal cortices and at least one of the following regions: amygdala, parahippocampal gyri, fusiform gyri. Patients who did not meet these criteria were considered to have a non-AD pathology (SNAP). Twenty-one patients were classified as AD and 15 as SNAP. We found a circumscribed tau tracer retention in the entorhinal cortices and/or amygdala in 5 amyloid-negative SNAP patients. At baseline, the SNAP patients were older and had lower ApoE ε4 allele frequency than the AD patients, but both groups did not differ regarding the neuropsychological testing and medial temporal lobe atrophy. During the 2-year follow-up, the episodic memory and language decline, as well as the temporo-parietal atrophy progression, were more pronounced in the AD sub-group, while the SNAP patients had a more pronounced progression of atrophy in the frontal lobes. Longitudinal tau tracer binding increased in AD patients but remained stable in SNAP patients. At baseline, distinct amyloid and tau PET signatures differentiated early AD and SNAP patients despite identical cognitive profiles characterized by an isolated ASHT and a similar degree of medial temporal atrophy. During the longitudinal follow-up, AD and SNAP patients diverged regarding clinical and imaging progression. Among SNAP patients, tau PET imaging could detect a tauopathy restricted to the medial temporal lobes, which was possibly explained by primary age-related tauopathy.

Factors Associated with Cognitive Outcomes After First-Ever Ischemic Stroke: The Impact of Small Vessel Disease Burden and Neurodegeneration.

Differences exist regarding post-stroke cognitive outcomes. The aim of this study investigates the potential factors associated with post-stroke cognitive performance and trajectories. We performed a prospective cohort study using serial monitoring of cognitive function over a 1-year period after a first-ever ischemic stroke. Small vessel disease (SVD) burden and hippocampal atrophy (HA) were evaluated using the modified cerebral small vessel disease scores (mCSVD) and medial temporal atrophy score (MTA) scores. A generalized estimating equation (GEE) model and a group-based trajectory model (GBTM) was used to analyze the potential factors associated with post-stroke cognitive outcomes. A total of 112 patients were enrolled. The GEE model showed that all patients, regardless of initial cognitive performance, had a tendency to show an increase in the Montreal Cognitive Assessment over time. The cognitive performance was better in male patients with higher education levels (p = 0.046 and p < 0.001, respectively), but tended to be worse in patients with higher SVD burden and HA. The GBTM model grouped patients into low, intermediate, and high performance (LP, IP, and HP) after stroke. A higher SVD burden, rather than HA and initial stroke severity and location, independently predicted a higher odds of poor post-stroke cognitive trajectory (being in the LP group) after stroke (adjusted odds ratio 2.74, 95%CI 1.09-6.86). In patients with first-ever mild stroke, cognitive improvement over time was evident. The detrimental impact of the SVD burden may outweigh the effect of HA or acute stroke insult on the post-stroke cognitive trajectory during the 1-year follow-up.

Esthetics outcomes in patients submitted to pterional craniotomy and its variants: A scoping review.

Background: Highly performed nowadays, the pterional craniotomy (PC) has several widespread variants. However, these procedures are associated with complications such as temporalis muscle atrophy, facial nerve frontal branch damage, and masticatory difficulties. The postoperative cranial aesthetic is, nonetheless, the main setback according to patients. This review aims to map different pterional approaches focusing on final aesthetics.Methods: This review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Studies were classified through the Oxford method. We searched PubMed/MEDLINE, EMBASE, and Cochrane Library from January 1969 to February 2021 for cohorts and randomized clinical trials that met our inclusion criteria.Results: 1484 articles were initially retrieved from the databases. 1328 articles did not fit the inclusion criteria. 118 duplicates were found. 38 studies were found eligible for the established criteria. 27 (71.05%) were retrospective cohorts, with low evidence level. Only 5 (13.15%) clinical trials were found eligible to the criteria. The majority of the studies (36/38) had the 2B OXFORD evidence level. A limited number of studies addressed cosmetic outcomes and patient satisfaction. The temporal muscle atrophy or temporal hollowing seems to be the patient’s main complaint. Only 17 (44.73%) studies addressed patient satisfaction regarding the aesthetics, and only 10 (26.31%) of the studies reported the cosmetic outcome as a primary outcome. Nevertheless, minimally invasive approaches appear to overcome most cosmetic complaints and should be performed whenever possible.Conclusion: There are several variants of the classic PC. The esthetic outcomes are poorly evaluated. The majority of the studies were low evidence articles.

Total Cerebral Small Vessel Disease Burden on MRI Correlates With Medial Temporal Lobe Atrophy and Cognitive Performance in Patients of a Memory Clinic.

Background: Cerebral small vessel disease (cSVD) and neurodegeneration are the two main causes of dementia and are considered distinct pathological processes, while studies have shown overlaps and interactions between the two pathological pathways. Medial temporal atrophy (MTA) is considered a classic marker of neurodegeneration. We aimed to investigate the relationship of total cSVD burden and MTA on MRI using a total cSVD score and to explore the impact of the two MRI features on cognition.Methods: Patients in a memory clinic were enrolled, who underwent brain MRI scan and cognitive evaluation within 7 days after the first visit. MTA and total cSVD score were rated using validated visual scales. Cognitive function was assessed by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales. Spearman's correlation and regression models were used to test (i) the association between MTA and total cSVD score as well as each cSVD marker and (ii) the correlation of the MRI features and cognitive status.Results: A total of 312 patients were finally enrolled, with a median age of 75.0 (66.0–80.0) years and 40.7% (127/312) males. All of them finished MRI and MMSE, and 293 subjects finished MoCA. Of note, 71.8% (224/312) of the patients had at least one of the cSVD markers, and 48.7% (152/312) of them had moderate–severe MTA. The total cSVD score was independently associated with MTA levels, after adjusting for age, gender, years of education, and other vascular risk factors (OR 1.191, 95% CI 1.071–1.324, P = 0.001). In regard to individual markers, a significant association existed only between white matter hyperintensities and MTA after adjusting for the factors mentioned above (OR 1.338, 95% CI 1.050–1.704, P = 0.018). Both MTA and total cSVD score were independent risk factors for MMSE ≤ 26 (MTA: OR 1.877, 95% CI 1.407–2.503, P < 0.001; total cSVD score: OR 1.474, 95% CI 1.132–1.921, P = 0.004), and MoCA < 26 (MTA: OR 1.629, 95% CI 1.112–2.388, P = 0.012; total cSVD score: OR 1.520, 95% CI 1.068–2.162, P = 0.020). Among all the cSVD markers, microbleed was found significantly associated with MMSE ≤ 26, while no marker was demonstrated a relationship with MoCA < 26.Conclusion: Cerebral small vessel disease was related to MTA in patients of a memory clinic, and both the MRI features had a significant association with cognitive impairment.

Cortical disconnection in temporal lobe epilepsy

A critical concept in neurology is cortical disconnection, in which seemingly normal gray matter can have reduced function due to loss of white matter (WM) connections. White matter damage has been extensively described in temporal lobe epilepsy (TLE), but the anatomical distribution of cortical disconnection in TLE is not fully characterized. Here, we studied 221 participants (64 left-TLE, 55 right-TLE, 102 controls) from three different epilepsy treatment centers. We employed a group connectometry diffusion imaging tractography approach to identify WM fibers with reduced integrity in TLE. We then assessed the anatomical distribution of the gray matter endpoint projections of abnormal fibers to map the anatomical pattern of disconnections. As expected, left- and right-TLE were associated with multiple WM pathways with reduced integrity, which were associated with extensive cortical disconnection involving predominantly limbic structures. Controlling for medial temporal gray matter atrophy, cortical disconnection of the left cingulum and the thalamus as well as disconnection of the bilateral putamen and the amygdala was associated with lower verbal memory immediate recall.In conclusion, our results support that cortical disconnection is an underappreciated but pervasive phenomenon in TLE, and cortical disconnection of limbic structures beyond the medial temporal regions is related to verbal memory performance.

Diamond-Shaped Mini-Craniotomy: A New Concept in Neurosurgery.

We describe, step by step, a modified, less invasive, diamond-shaped mini-craniotomy that optimizes dural opening and can be performed in elderly patients affected by acute subdural or intracerebral hematomas, in therapy with antiplatelets or anticoagulants. We retrospectively analyzed the clinical records of 67 patients (mean age of 78.5 years) treated in our institution, during a period of 10 years, with this novel diamond-shaped craniotomy. Seventeen patients were treated for intracerebral hemorrhage and 50 patients for acute subdural hematomas. All the patients were in therapy with antiplatelets or anticoagulants. Approach-related complications were not detected. Ten of 67 patients (14.9%) presented temporal muscle atrophy; there was no scar deformity, paresthesia, hyperalgesia, or ramus frontalis palsy around the scalp incision. Thirty-day mortality was 22%. The mean follow-up was 1.3 years. One-month postoperative brain computed tomography scans showed a satisfactory hematoma evacuation in 57 of 67 patients (85%). The diamond-shaped mini-craniotomy for acute subdural and intracerebral hematomas is safe and effective, and it should be considered as an alternative to traditional approaches, particularly in elderly patients.

Local Pterional Advancement Flap: A Minimally Invasive Option to Reconstruct Spheno-Temporal Extracranial Soft Tissues Dehiscences in Fragile Patients.

Late-onset, extracranial soft tissues dehiscence in the spheno-temporal region after major neurosurgical procedures might represent a potentially life-threatening complication.Due to surgery-related galeal/pericranial and myofascial temporal atrophy, classical regional flaps are often unavailable, enforcing potential indication for free vascularized flaps.Nevertheless, in elderly multioperated patients, who are not eligible for major surgery, it becomes mandatory to consider less invasive options for reconstruction.Authors describe the application of a reconstructive option for late-onset, pterional soft tissues dehiscence in fragile patients, using a local pterional advancement flap. Technique is stepwise described and illustrated in its clinical application. Local pterional advancement flap provides an excellent coverage, being extremely pliable, and flexible in contents and design. Vascular pedicle is independent from distal branches of the superficial temporal artery and provides adequate blood flow. Pedicle length enables a good arc of rotation, which facilitates its transposition. Flap preparation is very easy and minimally time consuming, due to its immediate regional availability and the easy harvesting technique. Local pterional advancement flap represents an effective option as regional flap for the reconstruction of late-onset, pterional soft tissues dehiscence in fragile patients.

FTLD Patient\u2013Derived Fibroblasts Show Defective Mitochondrial Function and Accumulation of p62

Frontotemporal lobar degeneration (FTLD) is a clinically, genetically, and neuropathologically heterogeneous group of neurodegenerative syndromes, leading to progressive cognitive dysfunction and frontal and temporal atrophy. C9orf72 hexanucleotide repeat expansion (C9-HRE) is the most common genetic cause of FTLD, but pathogenic mechanisms underlying FTLD are not fully understood. Here, we compared cellular features and functional properties, especially related to protein degradation pathways and mitochondrial function, of FTLD patient–derived skin fibroblasts from C9-HRE carriers and non-carriers and healthy donors. Fibroblasts from C9-HRE carriers were found to produce RNA foci, but no dipeptide repeat proteins, and they showed unchanged levels of C9orf72 mRNA transcripts. The main protein degradation pathways, the ubiquitin–proteasome system and autophagy, did not show alterations between the fibroblasts from C9-HRE-carrying and non-carrying FTLD patients and compared to healthy controls. An increase in the number and size of p62-positive puncta was evident in fibroblasts from both C9-HRE carriers and non-carriers. In addition, several parameters of mitochondrial function, namely, basal and maximal respiration and respiration linked to ATP production, were significantly reduced in the FTLD patient–derived fibroblasts from both C9-HRE carriers and non-carriers. Our findings suggest that FTLD patient–derived fibroblasts, regardless of whether they carry the C9-HRE expansion, show unchanged proteasomal and autophagic function, but significantly impaired mitochondrial function and increased accumulation of p62 when compared to control fibroblasts. These findings suggest the possibility of utilizing FTLD patient–derived fibroblasts as a platform for biomarker discovery and testing of drugs targeted to specific cellular functions, such as mitochondrial respiration.

Prediction of Subtle Cognitive Decline in Normal Aging: Added Value of Quantitative MRI and PET Imaging.

Quantitative imaging processing tools have been proposed to improve clinic-radiological correlations but their added value at the initial stages of cognitive decline is still a matter of debate. We performed a longitudinal study in 90 community-dwelling elders with three neuropsychological assessments during a 4.5 year follow-up period, and visual assessment of medial temporal atrophy (MTA), white matter hyperintensities, cortical microbleeds (CMB) as well as amyloid positivity, and presence of abnormal FDG-PET patterns. Quantitative imaging data concerned ROI analysis of MRI volume, amyloid burden, and FDG-PET metabolism in several AD-signature areas. Multiple regression models, likelihood-ratio tests, and areas under the receiver operating characteristic curve (AUC) were used to compare quantitative imaging markers to visual inspection. The presence of more or equal to four CMB at inclusion and slight atrophy of the right MTL at follow-up were the only parameters to be independently related to the worst cognitive score explaining 6% of its variance. This percentage increased to 24.5% when the ROI-defined volume loss in the posterior cingulate cortex, baseline hippocampus volume, and MTL metabolism were also considered. When binary classification of cognition was made, the area under the ROC curve increased from 0.69 for the qualitative to 0.79 for the mixed imaging model. Our data reveal that the inclusion of quantitative imaging data significantly increases the prediction of cognitive changes in elderly controls compared to the single consideration of visual inspection.

Interrelations of Cerebral Hemodynamics with Parameters of Cardiac Function and Brain Tissue in Patients with Ischemic Stroke.

We analyzed interrelations between the cerebral blood flow, cardiac output, and condition of the brain substance in 530 patients with ischemic stroke. Dependencies between the linear blood flow velocities in all arteries supplying the brain, as well as between the total volume blood flow through the internal carotid arteries and left ventricular stroke volume were revealed. The severity of atrophy was maximum in the parietal lobes (median 1.5 (1.0; 2.0)) and minimum in the occipital lobes (median 0.5 (0; 1.0)). Temporal lobes cortical atrophy significantly correlated with changes in the limbic system and in the periventricular and deep white matter; a significant weak inverse correlation of this parameter with blood flow in the middle cerebral artery was also found. Changes in the periventricular white matter (but not in deep white matter) demonstrated a significant inverse correlation with blood flow in the middle and anterior cerebral arteries.

Assessing the practice of written referrals to neuroradiology and how this process can be improved and standardised

AimsThis quality improvement project aims to improve the quality of information provided in the referrals from the older adult psychiatry department to radiology when requesting neuroradiological imaging.The secondary outcome aims to standardise information on the referral proforma. We hypothesise that this improved referral proforma will lead to improved quality of reporting from the radiology department, which will form the second stage of this quality improvement project.A further area of interest of this exercise is to establish whether standardised radiological scoring systems are requested in the referral, as these can be utilised as a means to standardise reported information.MethodRetrospective electronic case analysis was performed on 50 consecutive radiology referrals for a period of 3 months from November 2019 to January 2020. Data were obtained from generic MRI and CT referral proforma and entered into a specifically designed data collection tool. Recorded were patient demographics, provisional diagnosis, modality of imaging, use of ACE-III cognitive score, radiological scoring systems, and inclusion and exclusion criteria.ResultResults from 50 referrals have shown: 60% were male, 40% female. Average patient age of 74, ranging from 49 to 95. 58% were referred for CT head with 42% for MRI head. More than half of referrals quoted the ACE-III score. 26% of referrals stated exclusion criteria such as space occupying lesions, haemorrhages or infarcts. 10% of referrals requested specific neuro-radiological scoring scales. Specific scales which were requested included GCA (global cortical atrophy), MTA scale (medial temporal atrophy), Koedam scale (evidence of parietal atrophy) and Fazekas (evidence of vascular changes). Only 80% of referrals included the patients GP details on the referral form.Conclusion1. This quality improvement initiative has highlighted that the current level of information in referring patient to radiology is variable and dependent on the referrer.2. All referrals should state exclusion criteria as per the NICE guidelines on neuroimaging in diagnosis of dementia.3. Preliminary evidence suggests that requesting specific radiological rating scales could improve the quality of information received in the imaging report. The second part of this quality improvement initiative will aim to explore the impact of requesting these scales routinely.

Sarcopenia is independently associated with parietal atrophy in older adults

As populations age, sarcopenia becomes a major health problem among adults aged 65years and older. However, little information is available about the relationship between sarcopenia and brain structure abnormalities. The objective of this study was to investigate associations between sarcopenia and brain atrophy in older adults and relationships with regional brain areas. This prospective cohort study recruited 102 retirement community residents aged 65years and older. All participants underwent gait speed measurement, handgrip strength measurement and muscle mass measurement by dual X-ray absorptiometry. Diagnosis of sarcopenia was made according to criteria of the Asian Working Group for Sarcopenia (AWGSOP). All patients underwent magnetic resonance imaging (MRI), and images were analysed for global cortical atrophy (GCA) (range 0-3), parietal atrophy (PA) (range 0-3) and medial temporal atrophy (MTA) (range 0-4). Among 102 older adult participants (81.4±8.2years), 47 (46.1%) were diagnosed with sarcopenia according to AWGSOP criteria. The sarcopenia group had more moderate to severe PA (Grade 2: 19.1% vs. 5.5%; grade 3:6.4% vs. 0%, P=0.016) and GCA (Grade 2: 40.4% vs. 18.2%, P=0.003) and a trend of more moderate to severe MTA (Grade 2: 46.8% vs. 30.9%; grade 3: 8.5% vs. 1.8%, P=0.098) than the non-sarcopenia group. In univariate logistic regression, sarcopenia was significantly associated with PA (OR 5.94, 95% CI 1.56-22.60, P=0.009), GCA (OR 3.05, 95% CI 1.24-7.51, P=0.015), and MTA (OR 2.55, 95% CI 1.14-5.69, P=0.023). In multivariable logistic regression analysis, sarcopenia was an independent risk factor for PA (adjusted OR 6.90, 95% CI 1.30-36.47, P=0.023). After adjusting for all covariates, only age had a significant relationship with GCA (Adjusted OR 1.09, 95% CI 1.00-1.19, P=0.044) and MTA (Adjusted OR 1.09, 95% CI 1.01-1.17, P=0.022). This is the first study to explore associations between sarcopenia and global as well as regional brain atrophy in older adults. The sarcopenia group had higher rates of moderate to severe PA, GCA and MTA than the non-sarcopenia group. PA was significantly associated with sarcopenia in older adults. Further longitudinal studies are needed to address the mechanism and pathogenesis of brain atrophy and sarcopenia.

Determinants of Cognitive Trajectories in Normal Aging: A Longitudinal PET-MRI Study in a Community-based Cohort.

The determinants of the progressive decrement of cognition in normal aging are still a matter of debate. Alzheimer disease (AD)-signature markers and vascular lesions, but also psychological variables such as personality factors, are thought to have an impact on the longitudinal trajectories of neuropsychological performances in healthy elderly individuals. The current research aimed to identify the main determinants associated with cognitive trajectories in normal aging. We performed a 4.5-year longitudinal study in 90 older community-dwellers coupling two neuropsychological assessments, medial temporal atrophy (MTA), number of cerebral microbleeds (CMB), and white matter hyperintensities (WMH) at inclusion, visual rating of amyloid and FDG PET at follow-up, and APOE genotyping. Personality factors were assessed at baseline using the NEO-PIR. Univariate and backward stepwise regression models were built to explore the association between the continuous cognitive score (CCS) and both imaging and personality variables. The number of strictly lobar CMB at baseline (4 or more) was related to a significant increase in the risk of cognitive decrement. In multivariable models, amyloid positivity was associated with a 1.73 unit decrease of the CCS at follow-up. MTA, WMH and abnormal FDG PET were not related to the cognitive outcome. Among personality factors, only higher agreeableness was related to better preservation of neuropsychological performances. CMB and amyloid positivity are the only imaging determinants of cognitive trajectories in this highly selected series of healthy controls. Among personality factors, higher agreeableness confers a modest but significant protection against the decline of cognitive performances.

MISIAN (Minimally Invasive Surgery for Treatment of Unruptured Intracranial Aneurysms): A Prospective Randomized Single-Center Clinical Trial With Long-Term Follow-Up Comparing Different Minimally Invasive Surgery Techniques with Standard Open Surgery

Unruptured intracranial aneurysms (UIAs) are increasingly diagnosed but treatment is still controversial. Although the descriptions and use of minimally invasive surgery (MIS) have increased, comparative studies with standard approaches are rare. MISIAN (Minimally Invasive Surgery for Treatment of Unruptured Intracranial Aneurysms) is a prospective randomized single-center clinical trial with long-term follow-up comparing different MIS techniques with standard open surgery for treatment of UIAs. We randomly allocated a standard pterional approach (PtA) or MIS (1:2) to 111 patients with UIAs of the anterior circulation (mean dome diameter, 6.4 mm; range, 3-20 mm). Patients selected for MIS underwent a second randomization between a transeyelid approach (TelA) or nanopterional approach (NPtA) (1:1). Forty-one patients were randomized to and treated with the PtA, 36 with the TelA, and 34 with the NPtA. Only patients treated with PtA had permanent facial nerve palsy (n= 4 [10%]; P= 0.032). MIS cosmetic results were considered better than those of PtA by independent observers (P < 0.001), and less temporal atrophy in the MIS group was also observed (P= 0.0034). The proportion of excellent results was higher in the TelA group than in the NPtA group (86% vs. 67.6%; P= 0.039). Patients undergoing MIS also reported consistently higher satisfaction and quality-of-life scores (P < 0.001). MIS is superior to standard PtA for microsurgical clipping of small UIAs of the anterior circulation in terms of cosmetic, satisfaction, and quality-of-life outcomes. The TelA or NPtA for UIAs did not show significant outcome differences at 12-18 months.

The predictive value of normal EEGs in dementia due to Alzheimer's disease.

ObjectiveTo determine differences in clinical presentation and disease progression between patients with dementia due to AD with visually normal and abnormal EEG recordings. We hypothesized that patients with normal electroencephalographs (EEGs) are a representation of the heterogeneity of AD. We expected this group to have a phenotype with relatively predominant hippocampal atrophy, memory deficits, and a slower disease progression.MethodsPatients were included based on diagnosis of dementia due to AD, positive amyloid and tau cerebrospinal fluid (CSF) biomarkers, and the availability of EEG recordings. Patients were categorized in groups of normal (N = 208) and abnormal (N = 336) EEG recordings based on visual assessment by experienced neurophysiologists. At baseline demographics, cognitive, MRI, and CSF measures were compared between groups. Cognitive data from follow‐up visits were assessed by linear mixed‐effects models (LMMs), and corrected for baseline value, sex, age, and educational level, to compare cognitive deterioration over time between groups.ResultsAbout 1 in 4.5 patients with AD dementia had a visually normal EEG and this group showed better overall cognitive performance compared to the abnormal group, where memory was the most prominent affected domain. The normal group showed less global and parietal but similar medial temporal atrophy. Follow‐up data showed a slower deterioration on all tested cognitive domains in the normal EEG group.InterpretationPatients with dementia due to AD and visually normal EEG recordings showed a milder clinical presentation and had a milder disease progression compared to patients with an abnormal EEG. These results provide evidence of clinical and biological heterogeneity within AD dementia.