Hippocampal volume in subjects at clinical high-risk for psychosis: A systematic review and meta-analysis

Several magnetic resonance imaging studies have reported reductions in hippocampal volume in patients with psychosis. It is unclear whether structural abnormalities predate illness onset.We conducted a detailed, systematic literature search for studies reporting hippocampal volume in subjects with clinical high-risk, compared to healthy controls. The overall sample size comprised 1429 subjects.Meta-analysis revealed no difference for left, but a small, albeit significant, difference for right hippocampal volume, such that clinical high-risk patients had slightly smaller hippocampal volume than healthy controls (g = 0.24, p = 0.0418). Meta-regression indicated a moderating effect of manual tracing approach, due to one outlying site. The small difference on the right side did not remain significant (g = 0.14, 95%CI = [−0.03–0.32], p = 0.11) after removal of this outlier.This meta-analysis suggests that there is no reduction in hippocampal volume before transition to psychosis and hippocampal volume cannot be used as a biomarker in clinical high-risk individuals.     

Invalidity of one actigraphy brand for identifying sleep and wake among infants

Study objectivesFew commercially available brands of actigraphs (ACT) have been subjected to rigorous validation with infant participants. The purpose of this study was to examine the agreement between concurrent polysomnography (PSG) and one brand of ACT (AW-64, Mitter Co. Inc.) using appropriate statistical techniques among a sample of healthy infants.MethodsTwenty-two healthy infants (14.1 ± 0.6 months) had one night of ankle ACT recording during research PSG at Kosair Children’s Hospital Sleep Research Center in Louisville, Kentucky. Macroanalyses were conducted using the Bland–Altman concordance technique to assess agreement between total sleep time (TST) and wake after sleep onset (WASO) simultaneously measured by PSG and ACT, using two ACT algorithm settings. Microanalyses were also calculated to examine sensitivity, specificity, and accuracy of ACT within each PSG-identified sleep state. Correlations were calculated between PSG-identified arousals and the discrepancies between ACT and PSG.ResultsThe Bland–Altman concordance technique revealed that ACT underestimated TST by 72.25 (SD = 61.48) minutes and by ?60 min among 54.55% of infants. Furthermore, ACT overestimated WASO by 13.85 (SD = 30.94) minutes and by ?30 min among 40.91% of infants. Sensitivity, specificity, and accuracy analyses revealed that ACT adequately identified sleep, but poorly identified wake. PSG and ACT discrepancies were positively associated with PSG-identified arousals (r = .45).ConclusionsImproved device and/or software development is needed before the AW-64 can be considered a valid method for identifying infant sleep and wake.     

Anxiety and avoidance in infants and toddlers with autism spectrum disorders: Evidence for differing symptom severity and presentation

Little is known about the symptoms of anxiety in very young children with autism spectrum disorders, particularly comparisons between Autistic Disorder (AD) and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS). In the current study, toddlers (i.e., 17–37 months of age) with diagnoses of either AD (N = 159) or PDD-NOS (N = 154) were compared to atypically developing toddlers who did not meet criteria for an autism spectrum disorder (N = 200). Results indicated an overall pattern whereby toddlers with AD had more severe anxious and avoidant symptoms than either toddlers with PDD-NOS or controls. Further, toddlers with PDD-NOS were significantly more severe than controls. Additional analyses examining specific differences between the groups on anxious and avoidant items were conducted as well. Overall, toddlers with AD appear to have more severe anxiety than either those with PDD-NOS or controls, who did not differ on many items.     

Prefrontal cortex volume deficit in schizophrenia: A new look using 3 T MRI with manual parcellation

In this study we use high resolution Magnetic Resonance imaging (MRI) and apply rigorous manual tracing criteria in order to assess volumetrically the prefrontal cortex (PFC) in schizophrenia. Previous MRI studies suggested PFC is included in neural systems necessary for emotional processing and cognition, and regional PFC abnormalities might, thus, lead to specific negative symptoms, as well as a frequent association of poorer performance in category switching. The aim of this study was to use 3 T imaging and reliable manual parcellation to determine if, as hypothesized, this higher precision would reveal additional MRI abnormalities in PFC in schizophrenia, and an association between PFC abnormalities and specific negative symptoms, as well as in category switching. Using 3-T MRI, 27 schizophrenia patients and 27 healthy controls were examined. PFC was manually parcellated into frontal pole, superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG). Left SFG (p = 0.004), bilateral MFG (left: p = 0.007; right: p = 0.007), and bilateral IFG (left: p < 0.001; right: p = 0.002) showed volume reduction. There were symptom associations between smaller left MFG volumes and more affective flattening (R = − 0.465, p = 0.015), and smaller left IFG volumes and poorer performance on the alternating semantic category test (R = 0.440, p = 0.025). In summary, 3-T imaging revealed widespread gyral volume deficits in PFC gyri, and specific associations with selective negative symptoms, such as affective flattening, and with deficits in cognitive switching.     

Putaminal volume and diffusion in early familial Creutzfeldt–Jakob Disease

BackgroundThe putamen is centrally implicated in the pathophysiology of Creutzfeldt–Jakob Disease (CJD). To our knowledge, its volume has never been measured in this disease. We investigated whether gross putaminal atrophy can be detected by MRI in early stages, when the diffusion is already reduced.MethodsTwelve familial CJD patients with the E200K mutation and 22 healthy controls underwent structural and diffusion MRI scans. The putamen was identified in anatomical scans by two methods: manual tracing by a blinded investigator, and automatic parcellation by a computerized segmentation procedure (FSL FIRST). For each method, volume and mean Apparent Diffusion Coefficient (ADC) were calculated.ResultsADC was significantly lower in CJD patients (697 ± 64 µm²/s vs. 750 ± 31 µm²/s, p < 0.005), as expected, but the volume was not reduced. The computerized FIRST delineation yielded comparable ADC values to the manual method, but computerized volumes were smaller than manual tracing values.ConclusionsWe conclude that significant diffusion reduction in the putamen can be detected by delineating the structure manually or with a computerized algorithm. Our findings confirm and extend previous voxel-based and observational studies. Putaminal volume was not reduced in our early-stage patients, thus confirming that diffusion abnormalities precede detectible atrophy in this structure.     

Age assessment based on dental calcification in individuals with Down syndrome

It is important to estimate both chronological age (CA) and maturational age of an individual, in order to perform orthopedic treatment or surgery, and in cases of lost documentation. Use of dental age (DA) for these purposes has been widely studied; however, the literature is scarce with regard to individuals with Down syndrome (DS), a prevalent condition worldwide. In this study the chronology of dental maturation was evaluated by analyzing the DA of individuals with DS based on the Chronological Mineralization Table proposed by Nolla (1960). Thus, second molars were evaluated in 57 panoramic radiographs of male and female individuals with DS, between 5 and 16 years-old. These data were compared with a control group of 191 nonsyndromic individuals of the same age group. Correlation between CA and DA was ascertained using Pearson's correlation coefficient (r), and the difference between these variables was measured using Student's t-test for paired samples and the method proposed by Bland and Altman. The difference between DA and CA was compared between the control and DS groups using Student's t-test for independent samples (α = 0.05). DA was slightly lower than the CA; however, this difference was only significant for females. The difference between DA and CA was not significant between individuals with DS and control group (both genders, p = 0.945; males, p = 0.542; females, p = 0.381). We concluded that dental maturation in individuals with DS occurs similarly to that of nonsyndromic individuals.     

Idiopathic normal-pressure hydrocephalus,cerebrospinal fluid biomarkers,and the cerebrospinal fluid tap test

Cerebrospinal fluid (CSF) biomarkers, including soluble amyloid β-42 (Aβ-42) and phosphorylated-tau (P-tau), reflect core pathophysiological features of Alzheimer’s disease (AD). AD is frequently a concomitant pathology in older patients with idiopathic normal-pressure hydrocephalus (iNPH), and somewhat similar altered CSF dynamics exist in both AD and iNPH. We therefore investigated relationships between lumbar CSF biomarkers Aβ-42 and P-tau and clinical parameters in iNPH patients, along with differences in these biomarkers between CSF tap test (CSFTT) responders and non-responders. Thirty-one iNPH patients (14 CSFTT responders and 17 CSFTT non-responders) were included in the final analysis. We found lower CSF Aβ-42 correlated with poor cognitive performance (r = 0.687, p < 0.001 for Korean Mini Mental State Examination; r = 0.568, p = 0.001 for Frontal Assessment Battery; r = −0.439, p = 0.014 for iNPH grading scale [iNPHGS] cognitive score; r = −0.588, p = 0.001 for Clinical Dementia Rating Scale), and lower CSF P-tau correlated with gait dysfunction (r = −0.624, p < 0.001 for Timed Up and Go Test; r = −0.652, p < 0.001 for 10 meter walking test; r = −0.578, p = 0.001 for Gait Status Scale; r = −0.543, p = 0.002 for iNPHGS gait score). In subgroup analysis, CSF P-tau/Aβ-42 ratios were significantly higher in CSFTT non-responders compared to responders (p = 0.027). Two conjectures are suggested. One, CSF biomarkers may play different and characteristic roles in relation to different iNPH symptoms such as cognition and gait. Two, comorbid AD pathology in iNPH patients may affect the response to the CSFTT. Larger studies using combinations of other biomarkers associated with AD would be necessary to evaluate these hypotheses.     

CMAP scan discontinuities: Automated detection and relation to motor unit loss

ObjectiveTo evaluate an automated method that extracts motor unit (MU) information from the CMAP scan, a high-detail stimulus–response curve recorded with surface EMG. Discontinuities in the CMAP scan are hypothesized to result from MU loss and reinnervation.MethodsWe introduce the parameter D50 to quantify CMAP scan discontinuities. D50 was compared with a previously developed manual score in 253 CMAP scans and with a simultaneously obtained motor unit number estimate (MUNE) in 173 CMAP scans. The effect of MU loss on D50 was determined with a simulation model.ResultsWe found a high agreement (sensitivity = 86.8%, specificity = 96.6%) between D50 and the manual score. D50 and MUNE were significantly correlated below 80 MUs (r = 0.65, n = 68, p < 0.001), but not when MUNE was larger than 120 MUs (r = 0.23, n = 59, p = 0.08).ConclusionsDiscontinuities in the CMAP scan as expressed by a decreased D50 are related to significant MU loss. The determination of D50 is objective, quantitative, and less time-consuming than both manual scoring and many existing MUNE methods.SignificanceD50 is potentially useful to monitor neurogenic disorders and moderate to severe MU loss.     

Volume,metabolites and neuroinflammation of the hippocampus in bipolar disorder – A combined magnetic resonance imaging and positron emission tomography study

BackgroundThe hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in bipolar I disorder (BD-I) patients versus healthy controls (HCs) with magnetic resonance imaging (MRI) and spectroscopy (MRS). We post hoc investigated whether hippocampal volume and hippocampal metabolites were associated with microglial activation and explored if potential illness modifying factors affected these hippocampal measurements and whether these were associated with experienced mood and functioning.Materials and methodsTwenty-two BD-I patients and twenty-four HCs were included in the analyses. All subjects underwent psychiatric interviews as well as an MRI scan, including a T1 scan and PRESS magnetic resonance spectroscopy (MRS). Volumetric analysis was performed with Freesurfer. MRS quantification was performed with LC Model. A subgroup of 14 patients and 11 HCs also underwent a successful [¹¹C]-(R)-PK11195 neuroinflammation positron emission tomography scan.ResultsIn contrast to our hypothesis, hippocampal volumes were not decreased in patients compared to HC after correcting for individual whole-brain volume variations. We demonstrated decreased N-acetylaspartate (NAA) + N-acetyl-aspartyl-glutamate (NAAG) and creatine (Cr) + phosphocreatine (PCr) concentrations in the left hippocampus. In the explorative analyses in the left hippocampus we identified positive associations between microglial activation and the NAA + NAAG concentration, between alcohol use and NAA + NAAG concentration, between microglial activation and the depression score and a negative relation between Cr + PCr concentration and experienced occupational disability. Duration of illness associated positively with volume bilaterally.ConclusionCompared to HCs, the decreased NAA + NAAG concentration in the left hippocampus of BD-I patients suggests a decreased neuronal integrity in this region. In addition we found a positive relation between microglial activation and neuronal integrity in vivo, corresponding to a differentiated microglial function where some microglia induce apoptosis while others stimulate neurogenesis.     

Peripheral expression of MAPK pathways in Alzheimer’s and Parkinson’s diseases

Alteration of mitogen-activated protein kinase pathways may cause aberrant protein phosphorylation and enhanced apoptosis in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Increased susceptibility of lymphocytes to apoptosis has been reported in AD. To our knowledge this is the first study to investigate the expression and phosphorylation status of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) in peripheral blood lymphocytes of 20 AD and 20 PD patients and 20 healthy controls using western blot analysis. Compared with controls, no significant difference of total p38MAPK or JNK levels were observed in AD and PD patients, whereas phosphorylated p38MAPK and phosphorylated JNK levels were significantly increased in the AD and PD groups (p < 0.001). However, the increased levels of the two phosphorylated kinases in AD versus PD patients presented no significant difference. Interestingly, phosphorylated p38MAPK and phosphorylated JNK levels were positively correlated with disease duration (r = 0.602, p = 0.005 and r = 0.561, p = 0.010, respectively) and negatively correlated with the Mini Mental State Examination score (r = −0.664, p = 0.001 and r = −0.578, p = 0.008, respectively) in AD patients. No correlations between protein levels and clinical variables were found in PD patients. Investigation of peripheral changes in the expression of p38MAPK and JNK may lead to the development of innovative biomarkers of neurodegenerative diseases, particularly for AD.     

At the boundary of the self: The insular cortex in patients with childhood-onset schizophrenia,their healthy siblings,and normal volunteers

The insular cortex (insula), whose normal function involves delineating the boundary between self and non-self stimuli, has been implicated in the pathophysiology of the positive symptoms of schizophrenia, including hallucinations and delusions. Childhood-onset schizophrenia (COS), that includes the onset of psychosis before age 13, is a severe and continuous form of the illness which shows profound and global progressive cortical brain abnormalities during adolescence which merge in the adult pattern with age. Using prospectively acquired anatomic brain magnetic resonance imaging (MRI) scans, a matched sample of COS patients, their nonpsychotic full siblings and healthy volunteers, we measured insular volume using the FreeSurfer automated software. COS patients (n = 98; 234 scans) had significantly lower right (p = 0.003), left (p < 0.001), and total (p < 0.001) insular volumes than healthy volunteers (n = 100; 248 scans). Right insular volume negatively correlated with positive symptoms as measured by the Scale for the Assessment of Positive Symptoms (SAPS) (p = 0.02), while both left (p = 0.01) and right (p = 0.006) insula volumes were positively correlated with overall functioning, as measured by the Children's Global Assessment Scale (CGAS) scores. COS siblings (n = 71; 153 scans), on the other hand, did not differ significantly from normal volunteers suggesting that the insular deficits are more related to the illness state than a familial endophenotype. These results also highlight the salience of the insula in positive symptoms of schizophrenia perhaps resulting from the inability to discriminate between self from the non-self in COS. Further work to connect insular deficits to other neurocircuitries is warranted.     

BDNF Val66Met polymorphism and hippocampal volume in neuropsychiatric disorders: A systematic review and meta-analysis

BackgroundBrain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis and synaptic plasticity in the central nervous system, especially in the hippocampus, and has been implicated in the pathophysiology of several neuropsychiatric disorders. Its Val66Met polymorphism (refSNP Cluster Report: rs6265) is a functionally relevant single nucleotide polymorphism affecting the secretion of BDNF and is implicated in differences in hippocampal volumes.MethodsThis is a systematic meta-analytical review of findings from imaging genetic studies on the impact of the rs6265 SNP on hippocampal volumes in neuropsychiatric patients with major depressive disorder, anxiety, bipolar disorder or schizophrenia.ResultsThe overall sample size of 18 independent clinical cohorts comprised 1695 patients. Our results indicated no significant association of left (Hedge's g = 0.08, p = 0.12), right (g = 0.07, p = 0.22) or bilateral (g = 0.07, p = 0.16) hippocampal volumes with BDNF rs6265 in neuropsychiatric patients. There was no evidence for a publication bias or any demographic, clinical, or methodological moderating effects.Both Val/Val homozygotes (g = 0.32, p = 0.004) and Met-carriers (g = 0.20, p = 0.004) from the patient sample had significantly smaller hippocampal volumes than the healthy control sample with the same allele. The magnitude of these effects did not differ between the two genotypes.ConclusionThis meta-analysis suggests that there is no association between this BDNF polymorphism and hippocampal volumes. For each BDNF genotype, the hippocampal volumes were significantly lower in neuropsychiatric patients than in healthy controls.     

Continuous positive airway pressure deepens sleep in patients with Alzheimer’s disease and obstructive sleep apnea

ObjectivePatients with Alzheimer’s disease (AD) and obstructive sleep apnea (OSA) experience disrupted sleep. This study examined the effect of continuous positive airway pressure (CPAP) on sleep parameters in AD patients with OSA.MethodsA randomized placebo-controlled trial of 3 weeks of therapeutic CPAP (tCPAP) vs. 3 weeks placebo CPAP (pCPAP) followed by 3 weeks tCPAP in patients with AD and OSA. Polysomnography data from screening after one night and after 3 weeks of treatment were analyzed. Records were scored for percent of each sleep stage, total sleep time (TST), sleep efficiency (SE), sleep period (SP), time in bed (TIB), sleep onset (SO), wake time after sleep onset (WASO), and arousals. A randomized design comparing one night of pCPAP to tCPAP and a paired analysis combining 3 weeks of tCPAP were performed.ResultsFifty-two participants (mean age = 77.8 years, SD = 7.3) with AD and OSA were included. After one treatment night, the tCPAP group had significantly less % Stage 1 (p = 0.04) and more % Stage 2 sleep (p = 0.02) when compared to the pCPAP group. In the paired analysis, 3 weeks of tCPAP resulted in significant decreases in WASO (p = 0.005), % Stage 1 (p = 0.001), arousals (p = 0.005), and an increase in % Stage 3 (p = 0.006).ConclusionIn mild to moderate AD patients with OSA, the use of tCPAP resulted in deeper sleep after just one night, with improvements maintained for 3 weeks.     

Quantification of subfield pathology in hippocampal sclerosis: A systematic review and meta-analysis

BackgroundThe utility of MRI-based hippocampal subfield volumetry as a diagnostic test for hippocampal sclerosis (HS) is based on the hypothesis that specific hippocampal subfields are differentially affected in HS. While qualitative studies suggest selective involvement of certain hippocampal subfields in this condition, whether quantifiable differences exist remains unclear. Neuronal density measurement is the most widely used technique for measuring subfield pathological change in HS. Therefore, a systematic review and meta-analysis of studies reporting neuronal densities in temporal lobe epilepsy was performed in order to quantify subfield pathology in hippocampal sclerosis.MethodsStudies were identified by searching the Medline and Embase databases using the search terms: cell count, hippocampus, and epilepsy. Of the 192 studies identified by the literature search, seven met all inclusion and exclusion criteria. Random effects meta-analyses were performed, comparing: (i) neuronal densities in control (n = 121) versus HS (n = 371) groups for subfields CA1-4; and (ii) amount of neuronal loss in HS between subfields CA1-4.ResultsStatistically significant neuronal loss was observed comparing HS to control groups in all subfields CA1-4 (p < 0.001 for all comparisons). Significantly greater neuronal loss was demonstrated in HS comparing CA1 versus CA2 (p < 0.001), CA3 (p = 0.005), and CA4 (p = 0.003). Greater pyramidal cell loss was also demonstrated in CA3 relative to the CA2 subfield (p = 0.003). No significant differences were identified comparing CA2 and CA4 (p = 0.39); or comparing CA3 and CA4 (p = 0.64).ConclusionsHS is characterized by pathology in all hippocampal subfields. Quantifiable differences exist in the involvement of specific hippocampal subfields in HS. Neuronal loss is greatest in CA1, intermediate in CA3 and CA4, and least in CA2. Further studies are required to determine if this pattern can be detected using in vivo MRI.     

Performance on an Alzheimer-selective odor identification test in patients with Parkinson's disease and its relationship with cerebral dopamine transporter activity

BackgroundPrevious studies have shown selective deficits of odor identification in both Parkinson's disease (PD) and Alzheimer's disease (AD). Brief, selective AD smell screening tests have been developed to identify subjects at risk of AD. The disease specificity of such screening tests has not been formally evaluated.ObjectiveTo evaluate the performance of an Alzheimer-selective odor identification test in patients with PD and its relationship with cerebral dopamine transporter (DAT) activity.MethodsPD patients (n = 44; Hoehn and Yahr stages I–III; 13f/31 m; mean age 59.3 ± 10.1) and 44 controls matched for gender and age completed the University of Pennsylvania Smell Identification Test (UPSIT). All patients had PD duration > 1 year and none had evidence of dementia. Using the UPSIT, we calculated performance on the 10 odors previously reported to be selective for AD risk (UPSIT-AD10). A subset of 29 PD patients also underwent brain DAT [¹¹C]β-CFT (2-β-carbomethoxy-3β-(4-fluorophenyl) tropane) PET imaging. DAT binding was assessed in the hippocampus, amygdala, ventral and dorsal striatum.ResultsUPSIT-AD10 scores were significantly lower in the patient (5.8 ± 2.1) compared to the control group (8.6 ± 2.4) (t = 5.8, P < 0.0001). However, UPSIT-AD10 performance in the PD patients did not correlate with striatal or mesolimbic DAT activity.ConclusionsHyposmia in PD and AD overlap and supposed Alzheimer-selective smell screening tests may not be specific for AD. However, the supposed AD-selective hyposmia scores in PD did not correlate with cerebral DAT binding and may reflect a non-dopaminergic olfactory mechanism.     

Understanding the associations among anxiety sensitivity,distress tolerance,and discomfort intolerance: A comparison of three models

Emerging work has identified several related constructs that appear to be relevant to anxiety psychopathology including anxiety sensitivity (AS), distress tolerance (DT) and discomfort intolerance (DI). AS refers to the fear of the consequences of anxiety-related sensations. DT measures tolerance of negative emotions, whereas DI measures tolerance of uncomfortable physical sensations. Questions, however, have been raised regarding the overlap among AS, DT, and DI. The present study conducted confirmatory factor analyses to test three models of emotional and physical tolerance to determine which model provided the best fit for the associations among AS, DT, and DI. Nonclinical individuals (N = 411) and individuals with anxiety psychopathology (N = 253) completed self-report questionnaires. Results supported a hierarchical factor structure with 2 higher order factors with AS as a lower order factor of DT. The implications of these findings for the conceptualization of the relationships among AS, DT, and DI are discussed.     

CYP46A1 variants influence Alzheimer's disease risk and brain cholesterol metabolism

BackgroundCholesterol 24S-hydroxylase (CYP46) catalyzes the conversion of cholesterol to 24S-hydroxycholesterol, the primary cerebral cholesterol elimination product. Only few gene variations in CYP46 gene (CYP46A1) have been investigated for their relevance as genetic risk factors of Alzheimer's disease (AD) and results are contradictory.MethodsWe performed a gene variability screening in CYP46A1 and investigated the effect of gene variants on the risk of AD and on CSF levels of cholesterol and 24S-hydroxycholesterol.ResultsTwo of the identified 16 SNPs in CYP46A1 influenced AD risk in our study (rs7157609: p = 0.016; rs4900442: p = 0.019). The interaction term of both SNPs was also associated with an increased risk of AD (p = 0.006). Haplotypes including both SNPs were calculated and haplotype G–C was identified to influence the risk of AD (p = 0.005). AD patients and non-demented controls, who were carriers of the G–C haplotype, presented with reduced CSF levels of 24S-hydroxycholesterol (p = 0.001) and cholesterol (p < 0.001).ConclusionOur results suggest that CYP46A1 gene variations might act as risk factor for AD via an influence on brain cholesterol metabolism.     

Correlation between cognitive function and the association fibers in patients with Alzheimer’s disease using diffusion tensor imaging

White matter (WM) changes, along with well-characterized cortical abnormalities, occur in patients with Alzheimer’s disease (AD). We investigated the integrity of WM tracts within association fibers by the use of fractional anisotropy (FA), and the relationship between FA values and cognitive function in patients with AD. Neuropsychological examination and conventional MRI, as well as diffusion tensor imaging, (DTI) were conducted on 12 patients with mild to moderate AD and 18 cognitively healthy volunteers. DTI was performed to measure FA in the bilateral inferior fronto-occipital fasciculus (IFOF) and the superior longitudinal fasciculus (SLF). Mini-Mental State Examination (MMSE) scores and Montreal Cognitive Assessment (MoCA) values were used to evaluate cognitive function and the Clinical Dementia Rating (CDR) scale was used as a staging tool for dementia severity. FA measures were analyzed and correlated with neuropsychological data. No patient showed any WM tract abnormality on either T1-weighted or T2-weighted MRI. However, the FA values in the bilateral IFOF and SLF and the MoCA scores in patients with AD were significantly decreased (p < 0.05) compared to the controls. Furthermore, the decreased FA values in the SLF were positively correlated with cognitive function (MMSE scores – right: r = 0.672, p = 0.033, left: r = 0.919, p < 0.01; MoCA values – right: r = 0.747, p = 0.013, left: r = 0.679, p = 0.031). Our findings confirmed that the loss of integrity of microstructural WM connectivity has a role in the cognitive decline of patients with AD. The data also suggest that the FA values of the SLF may be used as a clinical marker of cognitive function.     

Reproducibility of peroneal motor nerve conduction measurement in older adults

ObjectiveWhile neuropathy is common in the elderly, nerve conduction (NC) reproducibility in older adults is not well-established. We sought to evaluate intraobserver reproducibility of peroneal motor NC measures in a diverse sample of older adults.MethodsWe measured peroneal motor NC amplitude and velocity in a subset of participants (mean age = 82.9 ± 2.7, n = 62, 50% female, 51.6% black, 35.5% DM) in the Health, Aging, and Body Composition Study. Using coefficients of variation (CVs), intraclass correlation coefficients (ICCs), and Bland Altman Plots, we compared two sets of measurements taken by the same examiner hours apart on the same day.ResultsLow CVs (2.15–4.24%) and moderate to high ICCs (0.75–0.99) were observed. No systematic variation was found across measures. Despite small numbers in some subgroups, we found no differences in reproducibility by diabetes, race or study site.ConclusionNC measures have moderate to high intraobsever reproducibility in older adults and are not affected by diabetes, race, or gender.SignificanceThese data provide evidence to support use of these measures in aging research.     

rs2070424 of the SOD1 gene is associated with risk of Alzheimer's disease

ObjectiveOxidative stress plays an important role in Alzheimer's disease (AD) etiopathogenesis. There were several studies that showed impaired antioxidant defense system (ADS) enzymes expression or activity in AD patients. There are only few studies evaluating the importance of ADS gene single nucleotide polymorphisms (SNPs) as risk factors of AD. We evaluated association between chosen SNPs of the enzymes of the ADS and risk of AD.MethodsWe included 400 AD patients and 402 healthy controls. We studied rs1041740, rs4998557 and rs2070424 of the SOD1 gene, rs2855116, rs5746136 and rs4880 of the SOD2 gene and rs3448, rs1050450 and rs1800668 of the GPx-1 gene (real time PCR). To determine the APOE gene common polymorphism, two single-nucleotide polymorphisms (SNPs; NCBI SNPs rs429358 and rs7412) were genotyped (TaqMan assays, Applied Biosystems [ABI], Foster City, CA, USA). The genotype and gender frequencies were compared between the studied groups by the χ² test and mean age by the t-Student test.ResultsAmong all studied SNPs only rs2070424 of the SOD1 gene was a protective factor for AD in an additive (OR = 0.47; 95% CI = 0.30–0.74, p = 0.001) and recessive (OR = 0.47; 95% CI = 0.30–0.75, p = 0.002) models including age, gender and APOE gene status.Conclusionsrs2070424 polymorphism of the SOD1 gene is a risk factor for AD in Polish population. Allel G and genotype AG and GG are protective factors for AD.