A laser driven pulsed X-ray backscatter technique for enhanced penetrative imaging.

X-ray backscatter imaging can be used for a wide range of imaging applications, in particular for industrial inspection and portal security. Currently, the application of this imaging technique to the detection of landmines is limited due to the surrounding sand or soil strongly attenuating the 10s to 100s of keV X-rays required for backscatter imaging. Here, we introduce a new approach involving a 140 MeV short-pulse (< 100 fs) electron beam generated by laser wakefield acceleration to probe the sample, which produces Bremsstrahlung X-rays within the sample enabling greater depths to be imaged. A variety of detector and scintillator configurations are examined, with the best time response seen from an absorptive coated BaF2 scintillator with a bandpass filter to remove the slow scintillation emission components. An X-ray backscatter image of an array of different density and atomic number items is demonstrated. The use of a compact laser wakefield accelerator to generate the electron source, combined with the rapid development of more compact, efficient and higher repetition rate high power laser systems will make this system feasible for applications in the field. Content includes material subject to Dstl (c) Crown copyright (2014). Licensed under the terms of the Open Government Licence except where otherwise stated. To view this licence, visit http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: psi@ nationalarchives.gsi.gov.uk.

Investigating the Factor Structure of the Preclinical Alzheimer Cognitive Composite and Cognitive Function Index across Racial/Ethnic, Sex, and Aß Status Groups in the A4 Study.

BACKGROUND: Disparities in Alzheimer's disease (AD) are well-documented among different racial/ethnic groups and between sex/genders. Neuropsychological assessment provides important information about cognitive changes and can offer valuable insights into disparities. However, neuropsychological measures must be comparable across racial/ethnic and sex/gender groups to accurately interpret disparities. OBJECTIVES: To evaluate measurement invariance (equivalence) of the Preclinical Alzheimer Cognitive Composite (PACC) and the Cognitive Function Index across racial/ethnic, sex/gender, and ß-amyloid (Aß) status groups. DESIGN, SETTING, PARTICIPANTS: Cross-sectional analysis of screening data from the Anti-Amyloid in Asymptomatic AD (A4) Study. The study enrolled participants aged 65-85 from sites across the United States, Canada, Australia, and Japan. MEASUREMENTS: Participants completed the PACC and the Cognitive Function Index. Participants classified as cognitively normal also underwent a Positron Emission Tomography (PET) scan to determine Aß status. RESULTS: Participants self-identified as non-Hispanic White (n=5241), non-Hispanic Black (n=267), Asian (n=228), or Hispanic White (n=225) as well as male (n=2885) or female (n=3076). Among those who underwent a PET scan, 3115 were classified as Aß- and 1309 were classified as Aß+. We found support for a one-factor model for both the PACC and Cognitive Function Index across the full sample and in samples stratified by race/ethnicity, sex/gender, and Aß status. The one-factor model of the PACC and Cognitive Function Index demonstrated scalar measurement invariance across racial/ethnic, sex/gender, and Aß status groups. CONCLUSIONS: Our findings suggest that performance on the PACC and Cognitive Function Index can be compared across the racial/ethnic, sex/gender, and Aß status groups examined in this study.

Cerebral small vessel disease in aging and Alzheimer's disease: a comparative study using MRI and SPECT.

BACKGROUND: White matter hyperintensities (WMH) are associated with aging and are prevalent in various brain pathologies. The purpose of the current study was to characterize WMH perfusion in age-matched elderly controls (ECs) and patients with Alzheimer's disease (ADs). METHODS: Fifty ECs (23 men) and 61 ADs (33 men) underwent magnetic resonance imaging (MRI), 99mTc-ECD single-photon emission computed tomography (SPECT) and cognitive testing. Brain tissue type was classified on T1 weighted images, and WMH were identified on interleaved proton density/T2 weighted images. Co-registered MR images were used to characterize SPECT perfusion patterns. RESULTS: WMH perfusion was lower than normal appearing white matter (NAWM) perfusion (P < 0.001) in both EC and AD groups. There was no WMH perfusion difference between groups when considering the mean perfusion from all WMH voxels (P > 0.43). However, locations that were likely to be considered WMH tended to have lower perfusion in ADs compared with ECs. Perfusion gradients along watershed white matter regions were significantly different between EC and AD groups (P < 0.05). A relationship was found between the volume of a WMH lesion and its mean perfusion (P < 0.001) in both ECs and ADs. CONCLUSION: Global WMH were hypoperfused compared with NAWM to the same degree in EC and AD participants, which suggests a common WMH etiology between groups. However, white matter locations that were likely to contain WMH tended to be hypoperfused in ADs compared with healthy aging. This finding is suggestive of AD-specific pathology that reduces the perfusion at anatomic locations susceptible to the formation of WMH through either the neurodegenerative process or AD-related vasculopathy or both.

Lesion Explorer: a comprehensive segmentation and parcellation package to obtain regional volumetrics for subcortical hyperintensities and intracranial tissue.

Subcortical hyperintensities (SH) are a commonly observed phenomenon on MRI of the aging brain (Kertesz et al., 1988). Conflicting behavioral, cognitive and pathological associations reported in the literature underline the need to develop an intracranial volumetric analysis technique to elucidate pathophysiological origins of SH in Alzheimer's disease (AD), vascular cognitive impairment (VCI) and normal aging (De Leeuw et al., 2001; Mayer and Kier, 1991; Pantoni and Garcia, 1997; Sachdev et al., 2008). The challenge is to develop processing tools that effectively and reliably quantify subcortical small vessel disease in the context of brain tissue compartments. Segmentation and brain region parcellation should account for SH subtypes which are often classified as: periventricular (pvSH) and deep white (dwSH), incidental white matter disease or lacunar infarcts and Virchow-Robin spaces. Lesion Explorer (LE) was developed as the final component of a comprehensive volumetric segmentation and parcellation image processing stream built upon previously published methods (Dade et al., 2004; Kovacevic et al., 2002). Inter-rater and inter-method reliability was accomplished both globally and regionally. Volumetric analysis showed high inter-rater reliability both globally (ICC=.99) and regionally (ICC=.98). Pixel-wise spatial congruence was also high (SI=.97). Whole brain pvSH volumes yielded high inter-rater reliability (ICC=.99). Volumetric analysis against an alternative kNN segmentation revealed high inter-method reliability (ICC=.97). Comparison with visual rating scales showed high significant correlations (ARWMC: r=.86; CHIPS: r=.87). The pipeline yields a comprehensive and reliable individualized volumetric profile for subcortical vasculopathy that includes regionalized (26 brain regions) measures for: GM, WM, sCSF, vCSF, lacunar and non-lacunar pvSH and dwSH.

Visual rating versus volumetry to detect frontotemporal dementia.

BACKGROUND/AIMS: Automated, volumetrically defined atrophy in the left anterior cingulate (LAC) and anterior temporal regions (LAT) on MRI can be used to distinguish most patients with frontotemporal dementia (FTD) from controls. FTD and Alzheimer's disease (AD) can differ in the degree of anterior temporal atrophy. We explored whether clinicians can visually detect this atrophy pattern and whether they can use it to classify the 2 groups of dementia patients with the same accuracy. METHODS: Four neurologists rated atrophy in the LAC and LAT regions on MRI slices from 21 FTD, 21 controls, and 14 AD participants. Inter-rater reliability and diagnostic accuracy were assessed. RESULTS: All 4 raters agreed on the presence of clinically significant atrophy, and their atrophy scoring correlated with the volumes, but without translation into high inter-rater diagnostic agreement. CONCLUSIONS: Volumetric analyses are difficult to translate into routine clinical practice.

Visual acuity of snapper Pagrus auratus: effect of size and spectral composition.

Visual acuity of the commercially important sparid Pagrus auratus was tested using the optomotor response. Juvenile fish were categorized by size as group 1 (50 g), group 2 (100 g), group 3 (150 g), group 4 (300 g), group 5 (500 g) and group 6 (800 g). Group 3 fish demonstrated excellent visual acuity (minimum separable angle, M(SA), 1°), which was improved compared with the smaller fish groups (groups 1 and 2, M(SA), 2°). In the larger fish groups, however, a reduction in visual acuity was observed (groups 4, 5 and 6 M(SA), 4°). Group 2 (100 g) fish displayed positive optomotor responses in long wavelength light (red) but reduced responses in short wavelengths (blue). Red light sensitivity is beneficial for the estuarine lifestyle of these fish, where light is predominantly at long wavelengths. In contrast, group 6 (800 g) fish displayed improved acuity in blue and green light and reduced acuity in red light. Fish of this size move away from the estuary to open oceans, where light is predominantly in the shorter wavelengths (blue-green). These results support the sensitivity hypothesis for the relationship between fish visual systems and the light environment they inhabit.

A SPECT study of sleep disturbance and Alzheimer's disease.

BACKGROUND/AIMS: This study aimed to investigate the possible association of regional cerebral perfusion and sleep loss in Alzheimer's disease (AD). METHODS: 55 AD patients were characterized as having (SL) or not having (NSL) nocturnal sleep loss based on standard AD scales assessing sleep over the previous 4 weeks. (99m)Tc-ethylcysteinate dimer SPECT scans were performed in a relaxed, wakeful state. Whole-brain analysis using Statistical Parametrical Mapping (SPM5) was performed to compare perfusion across groups. In addition, the AD groups were compared to normal control (NC) subjects of comparable age and gender to provide a context for interpretation of findings. RESULTS: SPM analysis showed increased perfusion in the right middle frontal gyrus (R-MFG, Brodman area 9, p = 0.016, familywise-error-corrected) in SL versus NSL patients. Comparison with NC subjects confirmed that perfusion in the R-MFG among SL patients did not exceed that found in NCs (relative rather than absolute hyperperfusion). CONCLUSIONS: In this sample of mild-to-moderate AD patients, relative hyperperfusion in the R-MFG is associated with reports of SL. This region may play a role in regulating sleep.

Increased Diameters of the Internal Cerebral Veins and the Basal Veins of Rosenthal Are Associated with White Matter Hyperintensity Volume.

BACKGROUND AND PURPOSE: White matter hyperintensities on T2-weighted MR imaging are typical in older adults and have been linked to several poor health outcomes, including cognitive impairment and Alzheimer disease. The presence and severity of white matter hyperintensities have traditionally been attributed to occlusive arteriopathy, but recent evidence also implicates deep medullary venule collagenosis and associated vasogenic edema. Historically, postmortem analyses have been the sole way to analyze cerebral veins, but SWI can be now used to examine cortical veins in vivo. The aim of the current study was to determine whether there is an association between the diameters of the large draining cerebral veins/sinuses and white matter hyperintensity volume. MATERIALS AND METHODS: T2-weighted FLAIR and SWI were performed in 682 older adults without dementia (mean age, 73.9 ± 5.9 years; 59.1% women). Total and regional white matter hyperintensity volume was derived. We measured the diameters of 5 regions of the cerebral venous draining system: internal cerebral veins, basal veins of Rosenthal, superior sagittal sinus, vein of Galen, and straight sinus terminus. RESULTS: Increased diameter of the internal cerebral veins was associated with greater total white matter hyperintensity volume (ß = 0.09, P = .02) and regionally in the parietal (ß = 0.10, P = .006), frontal (ß = 0.09, P = .02), and temporal (ß = 0.09, P = .02) lobes. Increased diameter of the basal veins of Rosenthal was associated with greater total (ß = 0.10, P = .01), frontal (ß = 0.11, P = .003), and temporal (ß = 0.09, P = .02) white matter hyperintensity volume. CONCLUSIONS: Our results suggest that the caliber of the internal cerebral veins and of the basal veins of Rosenthal relates to regional white matter disease.

Remote spatial memory in an amnesic person with extensive bilateral hippocampal lesions.

The hippocampus may have a time-limited role in memory, being needed only until information is permanently stored elsewhere, or this region may permanently represent long-term allocentric spatial information or cognitive maps in memory. To test these ideas, we investigated remote spatial memory in K.C., a patient with bilateral hippocampal lesions and amnesia for autobiographical events. In his spatial knowledge, general aspects were preserved, but details were lost, a pattern that resembled his memory loss in other domains. K.C. performed normally on allocentric spatial tests of his neighborhood and the world. He had difficulty, however, in recognizing and identifying non-salient neighborhood landmarks, and in recognizing city locations on world maps. This suggests that the hippocampus is not crucial for maintenance and retrieval of remotely formed spatial representations of major landmarks, routes, distances and directions, but is necessary for specifying location details, regardless of when they were acquired.

The neuropathological signature of bulbar-onset ALS: A systematic review.

ALS is a multisystem disorder affecting motor and cognitive functions. Bulbar-onset ALS (bALS) may be preferentially associated with cognitive and language impairments, compared with spinal-onset ALS (sALS), stemming from a potentially unique neuropathology. The objective of this systematic review was to compare neuropathology findings reported for bALS and sALS subtypes in studies of cadaveric brains. Using Cochrane guidelines, we reviewed articles in MEDLINE, Embase, and PsycINFO databases using standardized search terms for ALS and neuropathology, from inception until July 16th 2016. 17 studies were accepted for analysis. The analysis revealed that both subtypes presented with involvement in motor and frontotemporal cortices, deep cortical structures, and cerebellum and were characterized by neuronal loss, spongiosis, myelin pallor, and ubiquitin+ and TDP43+ inclusion bodies. Changes in Broca and Wernicke areas - regions associated with speech and language processing - were noted exclusively in bALS. Further, some bALS cases presented with atypical pathology such as neurofibrillary tangles and basophilic inclusions, which were not found in sALS cases. Given the limited number of studies, all with methodological biases, further work is required to better understand neuropathology of ALS subtypes.

Assessing cognitive functioning in ALS: A focus on frontal lobe processes.

OBJECTIVE: It is generally acknowledged that at least 50% of individuals with amyotrophic lateral sclerosis (ALS) will exhibit cognitive deficits outside of the characteristic motor neuron involvement. However, a specific cognitive profile has been difficult to ascertain due to disease-related testing barriers and limitations in the sensitivity and specificity of available assessment methods. This study assessed the level of functioning of extramotor frontal cognitive processes in ALS, and the amount of change in the functioning in these processes over time as disease progresses. METHODS: Empirical tests validated for a model of frontal lobe functioning were modified into an assessment battery appropriate for individuals with ALS in a clinical setting (the ALS-CFB, Computerised Frontal Battery). Twenty ALS participants and 36 age- and education-matched neurologically healthy controls were tested, and a sub-sample of each group (11 ALS and 20 controls) re-tested after approximately nine months. RESULTS AND CONCLUSIONS: Compared to standard neuropsychological screening tests that did not show a difference between ALS participants and healthy controls, the ALS-CFB illustrated a profile of extramotor frontal dysfunction involving energisation (preparing the neural system to respond) and executive functions, a profile that may be indicative of the nature of neurodegeneration in ALS.

Temporal and Spatial Variances in Arterial Spin-Labeling Are Inversely Related to Large-Artery Blood Velocity.

BACKGROUND AND PURPOSE: The relationship between extracranial large-artery characteristics and arterial spin-labeling MR imaging may influence the quality of arterial spin-labeling-CBF images for older adults with and without vascular pathology. We hypothesized that extracranial arterial blood velocity can explain between-person differences in arterial spin-labeling data systematically across clinical populations. MATERIALS AND METHODS: We performed consecutive pseudocontinuous arterial spin-labeling and phase-contrast MR imaging on 82 individuals (20-88 years of age, 50% women), including healthy young adults, healthy older adults, and older adults with cerebral small vessel disease or chronic stroke infarcts. We examined associations between extracranial phase-contrast hemodynamics and intracranial arterial spin-labeling characteristics, which were defined by labeling efficiency, temporal signal-to-noise ratio, and spatial coefficient of variation. RESULTS: Large-artery blood velocity was inversely associated with labeling efficiency (P = .007), temporal SNR (P < .001), and spatial coefficient of variation (P = .05) of arterial spin-labeling, after accounting for age, sex, and group. Correction for labeling efficiency on an individual basis led to additional group differences in GM-CBF compared to correction using a constant labeling efficiency. CONCLUSIONS: Between-subject arterial spin-labeling variance was partially explained by extracranial velocity but not cross-sectional area. Choosing arterial spin-labeling timing parameters with on-line knowledge of blood velocity may improve CBF quantification.

Identification of penumbra and infarct in acute ischemic stroke using computed tomography perfusion-derived blood flow and blood volume measurements.

BACKGROUND AND PURPOSE: We investigated whether computed tomography (CT) perfusion-derived cerebral blood flow (CBF) and cerebral blood volume (CBV) could be used to differentiate between penumbra and infarcted gray matter in a limited, exploratory sample of acute stroke patients. METHODS: Thirty patients underwent a noncontrast CT (NCCT), CT angiography (CTA), and CT perfusion (CTP) scan within 7 hours of stroke onset, NCCT and CTA at 24 hours, and NCCT at 5 to 7 days. Twenty-five patients met the criteria for inclusion and were subsequently divided into 2 groups: those with recanalization at 24 hours (n=16) and those without (n=9). Penumbra was operationally defined as tissue with an admission CBF <25 mL x 100 g(-1) x min(-1) that was not infarcted on the 5- to 7-day NCCT. Logistic regression was applied to differentiate between infarct and penumbra data points. RESULTS: For recanalized patients, CBF was significantly lower (P<0.05) for infarct (13.3+/-3.75 mL x 100 g(-1) x min(-1)) than penumbra (25.0+/-3.82 mL x 100 g(-1) x min(-1)). CBV in the penumbra (2.15+/-0.43 mL x 100 g(-1)) was significantly higher than contralateral (1.78+/-0.30 mL x 100 g(-1)) and infarcted tissue (1.12+/-0.37 mL x 100 g(-1)). Logistic regression using an interaction term (CBFxCBV) resulted in sensitivity, specificity, and accuracy of 97.0%, 97.2%, and 97.1%, respectively. The interaction term resulted in a significantly better (P<0.05) fit than CBF or CBV alone, suggesting that the CBV threshold for infarction varies with CBF. For patients without recanalization, CBF and CBV for infarcted regions were 15.1+/-5.67 mL x 100 g(-1) x min(-1) and 1.17+/-0.41 mL x 100 g(-1), respectively. CONCLUSIONS: We have shown in a limited sample of patients that CBF and CBV obtained from CTP can be sensitive and specific for infarction and should be investigated further in a prospective trial to assess their utility for differentiating between infarct and penumbra.

Anterior-medial thalamic lesions in dementia: frequent, and volume dependently associated with sudden cognitive decline.

BACKGROUND: The anterior-medial thalamus (AMT), which is associated with memory processing, is severely affected by Alzheimer's disease pathology and, when damaged, can be the sole cause of dementia. OBJECTIVE: To assess the frequency of magnetic resonance imaging (MRI) hyperintensities affecting the AMT, and their relationship with sudden cognitive decline. METHODS: 205 consecutive participants from a university cognitive neurology clinic underwent clinical evaluation, neuropsychological testing and quantitative MRI. RESULTS: AMT hyperintensities >5 mm3 occurred in 0 of 34 normal controls but were found in 5 of 30 (17%) participants with cognitive impairment with no dementia (CIND), 9 of 109 (8%) patients with probable Alzheimer's disease, 7 of 17 (41%) with mixed disease and 8 of 15 (53%) with probable vascular dementia (VaD). AMT hyperintensities occurred more often in participants with stepwise decline than in those with slow progression (chi2 = 31.7; p<0.001). Of the 29 people with AMT hyperintensities, those with slow progression had smaller medial temporal width (p<0.001) and smaller anterior-medial thalamic hyperintensities (p<0.001). In a logistic regression model, both variables were significant, and the pattern of decline was correctly classified in 86% of the sample (Cox and Snell R2 = 0.56; p<0.001). Those with AMT hyperintensities >55 mm3 were likely to have stepwise decline in cognitive function regardless of medial temporal lobe width; in contrast, those with smaller AMT hyperintensities showed a stepwise decline only in the absence of medial temporal lobe atrophy. All patients with VaD had left-sided AMT hyperintensities, whereas those with CIND had right-sided AMT hyperintensities. CONCLUSIONS: AMT hyperintensities >55 mm3 probably result in symptomatic decline, whereas smaller lesions may go unrecognised by clinicians and radiologists. Only half of those with AMT hyperintensities had diagnoses of VaD or mixed disease; the other AMT hyperintensities occurred in patients diagnosed with Alzheimer's disease or CIND. These silent hyperintensities may nevertheless contribute to cognitive dysfunction. AMT hyperintensities may represent a major and under-recognised contributor to cognitive impairment.

Cholinesterase inhibitors slow decline in executive functions, rather than memory, in Alzheimer's disease: a 1-year observational study in the Sunnybrook dementia cohort.

To determine if there are differential treatment effects of second-generation cholinesterase inhibitors over one year, 130 patients (untreated=65, treated=65) meeting NINCDS-ADRDA criteria for mild or moderate probable AD underwent standardized cognitive testing at baseline and 12 months later at a university memory clinic. Patients were followed either prior to or after the availability of treatment and were matched on education and baseline Mini Mental State Examination (MMSE). A detailed medical history evaluation was conducted. In this well matched longitudinal observational cohort study, there were no differences in the prevalence of comorbid illnesses, concomitant medication use or vascular risk factors except for a greater number of treated patients with a previous history of smoking. Separate repeated measures MANCOVAs on the MMSE, Mattis Dementia Rating Scale (DRS), and its 5 subscores (attention, initiation/perseveration, conceptualization, construction and memory) (Bonferroni corrected), after covarying for the effects of smoking, and SSRI use, showed less decline over one year in the treated group in overall cognition and in all subscores of the DRS except for memory (effect sizes 0.5-0.7). Less decline was also seen in the treated group in function and in instrumental and basic activities of daily living as measured with the Disability Assessment for Dementia Scale (DAD) (effect sizes 0.4-0.8). Executive, language and visuospatial functions, rather than memory, appeared to be more amenable to stabilization over one year by cholinesterase inhibitors in AD.

Vascular Dysfunction in Leukoaraiosis.

BACKGROUND AND PURPOSE: The pathogenesis of leukoaraiosis has long been debated. This work addresses a less well-studied mechanism, cerebrovascular reactivity, which could play a leading role in the pathogenesis of this disease. Our aim was to evaluate blood flow dysregulation and its relation to leukoaraiosis. MATERIALS AND METHODS: Cerebrovascular reactivity, the change in the blood oxygen level-dependent 3T MR imaging signal in response to a consistently applied step change in the arterial partial pressure of carbon dioxide, was measured in white matter hyperintensities and their contralateral spatially homologous normal-appearing white matter in 75 older subjects (age range, 50-91 years; 40 men) with leukoaraiosis. Additional quantitative evaluation of regions of leukoaraiosis was performed by using diffusion (n = 75), quantitative T2 (n = 54), and DSC perfusion MRI metrics (n = 25). RESULTS: When we compared white matter hyperintensities with contralateral normal-appearing white matter, cerebrovascular reactivity was lower by a mean of 61.2% ± 22.6%, fractional anisotropy was lower by 44.9 % ± 6.9%, and CBF was lower by 10.9% ± 11.9%. T2 was higher by 61.7% ± 13.5%, mean diffusivity was higher by 59.0% ± 11.7%, time-to-maximum was higher by 44.4% ± 30.4%, and TTP was higher by 6.8% ± 5.8% (all P < .01). Cerebral blood volume was lower in white matter hyperintensities compared with contralateral normal-appearing white matter by 10.2% ± 15.0% (P = .03). CONCLUSIONS: Not only were resting blood flow metrics abnormal in leukoaraiosis but there is also evidence of reduced cerebrovascular reactivity in these areas. Studies have shown that reduced cerebrovascular reactivity is more sensitive than resting blood flow parameters for assessing vascular insufficiency. Future work is needed to examine the sensitivity of resting-versus-dynamic blood flow measures for investigating the pathogenesis of leukoaraiosis.

The behavioural neurology assessment.

BACKGROUND: We present information regarding the standardization, reliability and clinical validity of two versions of the Behavioural Neurology Assessment (BNA). The BNA-Long Form consists of 24 subtests within separate domains: Attention, Memory, Language, Visuospatial Function, Executive Function, and Praxis. The BNA-Short Form consists of 13 subtests within the domains of Attention, Memory, Naming, Visuospatial Function and Executive Function. In addition to individual domain indices, a Grand Total score was calculated for both BNA versions. OBJECTIVE: To standardize the administration and scoring and validate the BNA for detection of dementia. METHODS: Standardized normative data were obtained on 115 healthy subjects ranging in age from 50 to 95. Test-retest stability was obtained on 19 subjects and clinical validity was investigated by administering the BNA and Mini-Mental Status Examination (MMSE) to 29 patients with dementia and 29 age-matched healthy subjects (controls). RESULTS: Age had a significant effect on all but the Visuospatial and Praxis indices of the BNA-Long Form and an effect on Naming and Grand Total score of the Short-Form. Internal consistency (Cronbach's coefficient alpha) was .87 and .67 for the Long and Short Forms (.95 and .96 for dementia and control groups combined). Test-retest stability was acceptable. Grand Total indices of both BNA versions showed significant, positive correlations with the MMSE. Both BNA versions had superior sensitivity to dementia relative to the MMSE (.93 versus .79). Specificity was equivalent to the MMSE (.93 versus .97). CONCLUSIONS: Positive predictive values of the BNA and MMSE are equivalent but the BNA provides superior negative predictive value.

Linear width of the medial temporal lobe can discriminate Alzheimer's disease from normal aging: the Sunnybrook dementia study.

To discriminate Alzheimer's disease (AD) from healthy controls, the thinnest medial temporal lobe (tMTL) width on 3D-MRI was measured according to a newly developed method at the inter-collicular sulcus (ICS) level with scans aligned to the long axis of the hippocampus in 22 mild, 27 moderate probable AD patients and 41 healthy controls. For comparison, MTL width replicating the technique of Jobst et al. (jMTL) as well as hippocampal and parahippocampal volumes, were also measured. Using logistic regression taking into account age, sex, and education, tMTL width classified mild AD from controls with a sensitivity of 86%, specificity of 95% and accuracy of 92%. Similar values were obtained for moderate or total AD group versus controls. By comparison, jMTL width was only useful in distinguishing moderate AD from controls, and volumetric measures were equally sensitive in classifying mild and moderate AD in our sample. This quick, reliable, and standardized measurement of tMTL can be helpful in differentiating even mild AD from controls with reasonable accuracy.

A reliable MR measurement of medial temporal lobe width from the Sunnybrook Dementia Study.

We studied the hippocampal angle and spatial relationships of medial temporal lobe (MTL) structures, using midbrain colliculi and inter-collicular sulcus (ICS) as landmarks, and measured MTL width on axial 3D-T1-weighted MRI at ICS level in 41 normal, aged participants. Mean hippocampal angle was 29 degrees (range 17-42 degrees ) caudal to the anterior-posterior commissure (AC-PC) line. The slice at the ICS, parallel to the long axis of the hippocampus, best revealed a longitudinal view of hippocampus and parahippocampal gyrus in 76% of participants, compared to only 7% when slices were 20 degrees caudal to orbitomeatal line (OML), an accepted technique used to examine MTL width in previous CT studies. The MTL width measured midway and at its thinnest between the anterior-posterior borders of the midbrain was highly reproducible (intraclass correlation coefficients >0.98) using these new methods. These simple decision rules, individualized orientation along the hippocampus and using a standardized landmark like the ICS, make these measures more comparable across subjects, and hence more useful in detecting and monitoring MTL atrophy in dementia.