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Hui Guo,1,2 William Siu,1,3 Ryan CN D’Arcy,1,4 Sandra E Black,5,6 Lukas A Grajauskas,1,4 Sonia Singh,7,8 Yunting Zhang,2 Kenneth Rockwood,9,10 Xiaowei Song1,4,9 On behalf of The Alzheimer’s Disease Neuroimaging Initiative and the National Alzheimer’s Coordinating Center 1Health Sciences and Innovation, ImageTech Laboratory, Fraser Health Authority, Surrey, BC, Canada; 2Department of Diagnostic Imaging, Tianjin Medical University General Hospital, Tianjin, China; 3Department of Medical Imaging, Fraser Health Authority, Surrey, 4Departments of Applied Sciences and Computing Science, Simon Fraser University, Burnaby, BC, 5Department of Medicine (Neurology), 6LC Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre & University of Toronto, Toronto, ON, 7Department of Family Medicine, University of British Columbia, Vancouver, BC, 8Department of Research and Evaluation, Fraser Health, Surrey, BC, 9Department of Medicine (Geriatric Medicine), Dalhousie University, 10Centre for Healthcare of the Elderly, Nova Scotia Health Authority, Halifax, NS, Canada Purpose: One of the central features of brain aging is the accumulation of multiple age-related structural changes, which occur heterogeneously in individuals and can have immediate or potential clinical consequences. Each of these deficits can coexist and interact, producing both independent and additive impacts on brain health. Many of the changes can be visualized using MRI. To collectively assess whole-brain structural changes, the MRI-based Brain Atrophy and Lesion Index (BALI) has been developed. In this study, we validate this whole-brain health assessment approach using several clinical MRI examinations.Materials and methods: Data came from three independent studies: the Alzheimer’s Disease Neuroimaging Initiative Phase II (n=950; women =47.9%; age =72.7±7.4 years); the National Alzheimer’s Coordinating Center (n=722; women =55.1%; age =72.7±9.9 years); and the Tianjin Medical University General Hospital Research database on older adults (n=170; women =60.0%; age =62.9±9.3 years). The 3.0-Tesla MRI scans were evaluated using the BALI rating scheme on the basis of T1-weighted (T1WI), T2-weighted (T2WI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), and T2*-weighted gradient-recalled echo (T2*GRE) images.Results: Atrophy and lesion changes were commonly seen in each MRI test. The BALI scores based on different sequences were highly correlated (Spearman r2>0.69; P0.29; P26.48, P

Kira Bensimon,1,2 Nathan Herrmann,1,2,4 Walter Swardfager,1–4 Hao Yi,1 Sandra E Black,1–4 Fu-Qiang Gao,1,4 Abraham Snaiderman,2,3 Krista L Lanctôt1–4 1Sunnybrook Research Institute, Toronto, ON, Canada; 2Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 3Toronto Rehabilitations Institute,Toronto, ON, Canada; 4Canadian Partnership for Stroke Recovery, Heart and Stroke Foundation, Ottawa, ON Canada Background and purpose: Depression is a commonly occurring and persistent sequel of stroke affecting approximately 29% of patients. An immunological hypothesis has been put forward, and synthesis of kynurenine from tryptophan has been proposed to link inflammatory activity with neurotoxicity and neurotransmitter dysfunction. This study assessed the relationship between peripheral blood kynurenine and poststroke depressive symptoms.Patients and methods: This was a multisite cross-sectional observational cohort study of patients with ischemic stroke. Depressive symptoms were assessed using the Center for Epidemiological Studies Depression (CES-D) scale and divided into high, medium, and low depressive symptom tertiles. Concentrations of kynurenine and tryptophan were assayed from fasting serum samples, and the kynurenine/tryptophan ratio was compared between tertiles. Serum cytokine concentrations were assayed in a subgroup of patients, and the ratio of proinflammatory (IL-6, IL-18, IFNγ, TNF, IL-1β) to anti-inflammatory (IL-10) cytokines compared.NLM identifier: NCT00254020.Results: In these patients (n=86, 52.3% male, mean age 71.7±14.2 years), there were no differences in kynurenine/tryptophan ratios between CES-D scale tertiles (F2,76=0.04, P=0.96) controlling for relevant covariates. For cytokines (n=53), serum IL-1β concentrations (F2,52=3.55, P=0.037) and serum ratios of IL-18/IL-10 (F2,52=3.30, P=0.046), IFNγ/IL-10 (F2,52=4.02, P=0.025), and IL-1ß/IL-10 (F2,52=4.34, P=0.019) were elevated in the middle CES-D tertile. Post hoc analyses suggested that serum ratios of IL-18/IL-10 (ρ=0.28, P=0.04), and IL-1ß/IL-10 (ρ=0.43, P=0.001), as well as IL-1ß (ρ=0.29, P=0.04), were significantly associated with fatigue.Conclusion: Peripheral kynurenine/tryptophan ratios were not associated with depressive symptoms in a poststroke population. However, in exploratory analyses a proinflammatory bias was identified specifically in patients with mild depressive symptoms and associated with poststroke fatigue, suggesting an avenue for future research. Keywords: kynurenine, tryptophan, cytokine, inflammation, stroke, depression

Tiffany W Chow1–6, Ariel Graff-Guerrero4,6, Nicolaas PLG Verhoeff2–4,7, Malcolm A Binns3,8, David F Tang-Wai5,9, Morris Freedman1,3,5, Mario Masellis5,10, Sandra E Black3,5,10, Alan A Wilson4,6, Sylvain Houle4,6, Bruce G Pollock4,61Division of Neurology, 2Department of Psychiatry, 3Rotman Research Institute, Baycrest; 4Departments of Psychiatry, 5Medicine, Division of Neurology, University of Toronto; 6Centre for Addiction and Mental Health PET Centre; 7Kunin-Lunenfeld Applied Research Unit, Baycrest; 8Dalla Lana School of Public Health, University of Toronto; 9University Health Network Memory Clinic; 10LC Campbell Cognitive Neurology Research Unit, Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, Toronto, ON, CanadaBackground: Memantine has shown effects on cortical metabolism in Alzheimer's disease (AD), and the mechanism of action may not be specific to AD alone. We hypothesized that participants with frontotemporal dementia taking memantine would show an increased cortical metabolic activity in frontal regions, temporal regions, or in salience network hubs.Methods: Sixteen participants with behavioral or language variant frontotemporal dementia syndromes (FTD) were recruited from tertiary FTD clinics and treated with memantine hydrochloride 10 mg twice daily in this fixed-dose, open-label pilot study. The primary endpoint was enhancement of cortical metabolic activity after 7–8 weeks of treatment. Secondary endpoints were measures of mood and behavior disturbance, frontal executive function, and motor disturbance.Results: Voxel-wise parametric image analysis of positron emission tomography (PET) data from seven behavioral variant FTD patients, eight semantic dementia patients, and one progressive nonfluent aphasia patient, of mean age 64.3 years, mean duration of illness 4.25 years, and baseline mean sum of boxes Clinical Dementia Rating score 6.59, revealed an increase in [18F]-fluorodeoxyglucose (FDG) normalized metabolic activity in bilateral insulae and the left orbitofrontal cortex (P < 0.01). The increase on FDG-PET did not correlate with changes on behavioral inventories. Post hoc analysis indicated that semantic dementia participants drove this finding.Conclusion: This open-label clinical PET study suggests that memantine induces an increase in metabolism in the salience network in FTD. A placebo-controlled follow-up study is warranted.Keywords: Alzheimer's disease, frontotemporal dementia, metabolism, PET scan, semantic dementia

Objectives: To follow up on the increases we reported in normalized metabolic activity in salience network hubs from a 2-month open-label study of memantine in frontotemporal dementia (FTD).Methods: We repeated fluorodeoxyglucose positron emission tomography (FDG-PET) after 6 months of drug use and subjected the data to Statistical Parametrical Mapping (SPM) analysis to reveal clusters of significant change from baseline. We also sought correlations between changes in behavioral disturbances on the Frontal Behavioral Inventory (FBI) and the PET signal.Results: Recruitment of one progressive nonfluent aphasia and one behavioral variant FTD precluded statistical analysis for any FTD subtype other than semantic dementia (SD). The baseline-to-6-month interval showed increased normalized metabolic activity in the left orbitofrontal cortex (p < 0.002) for five participants with SD. The 2-6-month interval revealed a late increase in normalized metabolic activity in the left insula (p < 0.013), right insula (p < 0.009), and left anterior cingulate (p < 0.005). The right anterior cingulate showed both an initial increase and a delayed further increase (2-6 months, p < 0.016). FBI scores worsened by 43.3%. One participant with SD opted not to continue memantine beyond 2 months yet showed similar FDG-PET increases.Conclusions: Increases in normalized cortical metabolic activity in salience network hubs were sustained in SD over a 6-month period. Because one participant without medication also showed these changes, further investigation is recommended through a double-blind, placebo-controlled study with FDG-PET as an outcome measure. [ABSTRACT FROM AUTHOR]

Limb apraxia is a neurological disorder characterized by an inability to pantomime and/or imitate gestures. It is more commonly observed after left hemisphere damage (LHD), but has also been reported after right hemisphere damage (RHD). The Conceptual-Production Systems model (Roy, 1996) suggests that three systems are involved in the control of purposeful movements: the conceptual, the production and the sensory/perceptual system. Depending on which system is damaged different patterns of apraxia are expressed. To determine the apraxia pattern, pantomime, delayed, and concurrent imitation tasks need to be administered, as well as conceptual tasks assessing one's knowledge of actions. Based on the model, eight patterns of apraxia should emerge. The purpose of this study is to determine whether these patterns are in fact observed in stroke patients and examine their frequency. If the performance of most stroke patients falls into one of the patterns, then we would have strong support for the conceptual-production model. Stroke (34 LHD and 39 RHD) patients and 27 age- and education-matched healthy controls participated in the study. Participants were assessed in four task modalities: pantomime, delayed imitation, concurrent imitation and conceptual knowledge (two tasks were used: tool naming by action and action identification). Patients were categorized as impaired on a task if they scored 2 SD below the mean performance of the controls for gesture production tasks, or below a cut-off score on the conceptual tasks. They were then classified into patterns depending on their performance on the four task modalities. Most patients (86%) fell into one of seven patterns originally predicted from the Conceptual-Production Systems model. The two most common patterns were deficits in pantomime and imitation with preserved gesture recognition and conduction apraxia (selective deficit in imitation). Four new patterns emerged, but mostly single cases of these were found. Overall, the study provides strong support for the Conceptual-Production Systems model. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Alzheimer's disease (AD) burdens not only the person, but also the person's caregiver(s). This burden has been linked to negative health effects for caregivers. To that end, a survey of Canadian caregivers of persons with AD/other dementias was conducted to investigate the social, physical, psychological and financial impact of AD and/or dementia-related conditions on caregivers' quality of life. METHODS: A web-based survey, the Canadian Alzheimer's Disease Caregiver survey, was made available through the Canadian Alzheimer's Society website and 50plus.com, an internet portal for baby boomers (BB) (people aged 50 years or older), as well as through HarrisDecima Research's e-Vox panel. A total of 398 individuals completed the survey between 15 September and 5 November 2006. RESULTS: Of the 398 total respondents, 221 were identified as baby boomers who provided care to an individual with AD/dementia. Respondents identified several areas of burden of care. These included negative effects on emotional health (such as increased depression, more stress and greater fatigue), financial costs and a need to change a working situation (e.g. by retiring early, reducing work hours or refusing a promotion). CONCLUSION: Caregivers of persons with AD/related dementia face important social, physical, psychological and financial pressures. These negatively affect the quality of life of caregivers with a significant increased burden being placed on live-in caregivers versus caregivers who do not co-reside with their care recipients. Interventions that address these pressures will not only improve the health and well-being of caregivers, but likely also the care of persons with AD/dementia. Copyright (c) 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective Individuals with a clinical diagnosis of Alzheimer's disease (AD) may have prominent features of executive dysfunction and language impairment as well as behavioral abnormalities early in the disease ('high frontality'). When this occurs differentiation from frontotemporal dementia (FTD) is difficult. It is hypothesized that AD patients with high frontality may have clinical and pathological features that distinguish them from less frontal AD patients. Methods In a well-characterized cohort of people with cognitive impairment, we used the Frontal Behavioral Inventory (FBI) in an attempt to identify AD patients with prominent frontal features (high-FBI AD) and distinguish them from the remainder of AD patients (low-FBI AD). Results The 18 high-FBI AD patients were compared with the 26 FTD patients who had an FBI performed and the 53 other low FBI AD patients. The individual FBI items did not differ significantly between the FTD and the high-FBI AD patients, and the high FBI AD patients were more like the FTD patients than the other AD patients with respect to presence of a family history of AD, proportion with homozygous apolipoprotein E4 status, disability as measured by the Disability Assessment for Dementia (DAD) Scale and the Functional Rating Scale (FRS) and neuropsychiatric impairment as measured by the Neuropsychiatric Inventory (NPI). Memory symptom duration was similar in the high FBI AD group compared to the low FBI AD group. Conclusions There is a subgroup of AD patients with high frontality that can be clinically distinguished from the remainder of AD patients but which requires pathological verification. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Prehospital Code Stroke triage has the potential to overwhelm stroke centres by falsely identifying patients as eli gible for fibrinolysis. We sought to determine whether online medical control (whereby paramedics contact the medical control physician before a Code Stroke triage is assigned) reduced the proportion of false-positive Code Stroke patients. METHODS: Following the introduction of a protocol for prehospi tal Code Stroke triage in an urban centre, online medical control alternated with off-line medical control (whereby paramedics implement Code Stroke triage independently) over 4 discreet intervals. We reviewed data for patients triaged to 3 regional stroke centres to compare the proportion of false-positive Code Stroke patients during online versus off-line medical control. We predefined false positives as patients triaged as Code Stroke who had symptoms discovered on awakening, were last seen in their usual state of health greater than 2 hours before assess ment or had a final diagnosis other than stroke. RESULTS: The proportion of false positives was lower during online medical control (31% v. 42%, p = 0.003). This was explained by a lower proportion of patients whose symptoms were discovered on awakening (8% v. 14%, p < 0.001) and who were last seen in their usual state of health greater than 2 hours before assessment (22% v. 32%, p = 0.005). A final diagnosis of stroke was similar in the 2 groups (77% v. 79%, p = 0.39), as was the proportion of patients receiving fibrinol ysis (35% v. 33%, p = 0.72). Eighteen percent of patients were denied Code Stroke triage during online control, most com monly because of the time of symptom onset. CONCLUSION: Online medical control is associated with a reduced proportion of false-positive Code Stroke triage. [ABSTRACT FROM AUTHOR]

Background/Aims: The relationship between subcortical hyperintensities (SH) on brain MRI and gait parameters in aging and Alzheimer's disease (AD) is unclear. This study compared gait in 42 mild AD patients to 22 normal controls (NC) based on their SH severity and correlated them to SH burden in these groups. Methods: Gait velocity, stride length, cadence and step width were captured on an automated walkway. Severity of SH on MRI was visually scored, which was used to dichotomize the AD and NC groups into high and low SH severity subgroups. Correlations between gait parameters and total and regional distribution of SH were explored. Results: Compared to both AD subgroups and the NC subgroup with high SH severity, the NC subgroup with low SH severity had a significantly faster velocity (127 cm/s). Overall SH severity correlated significantly with stride length and velocity in the AD (r = -0.4, p = 0.01) and NC (r = -0.4, p = 0.02) groups, respectively, specifically with SH severity in the frontal and basal ganglion regions. Conclusion: SH burden may have a relatively stronger association with slower gait velocity in NC than in patients with mild AD. The fronto-subcortical SH load may influence gait in AD and aging. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the role of the dopaminergic brain reward system (BRS) in apathy associated with Alzheimer disease (AD). DESIGN: BRS function was probed in 20 AD patients using dextroamphetamine (d-amph) challenge. After baseline behavioral testing, patients were given a single 10 mg dose of d-amph. The time course of the subjective response to d-amph was assessed at hourly intervals for 4 hours. SETTING: Three outpatient dementia clinics associated with a university-affiliated hospital. PARTICIPANTS: Twenty AD patients aged 77 +/- 8 years with Neuropsychiatric Inventory (NPI) apathy scores of 3.4 +/- 3.5 and Mini-Mental State Examination scores of 20.4 +/- 5.1. MEASUREMENTS: Patients were classified as apathetic based on an NPI apathy subscore of > or =4. Apathy severity was assessed using the Apathy Evaluation Scale (AES). The subjective and behavioral responses to d-amph were assessed using computerized versions of the Addiction Research Centre Inventory (ARCI), Profile of Mood States and Connor's Continuous Performance Task. RESULTS: Repeated measures ANOVA revealed a significant interaction between the presence of apathy and the peak subjective response to d-amph on the ARCI, such that while nonapathetic AD patients were responsive to the rewarding effects of d-amph, apathetic patients were not (F(1,17) = 4.93, p = 0.04). Continuous AES scores were predicted by peak ARCI positive effects scores and baseline overall behavioral disturbances (NPI total) in a backward linear regression analysis using the entire study sample (F(2,17) = 10.00, p = 0.01, R(2) = 0.49). CONCLUSIONS: Apathy in AD is associated with a blunted subjective response to d-amph, which may be indicative of dysfunction in the BRS. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients with cognitive impairment no dementia (CIND) are at an increased risk of progression to Alzheimer's disease (AD). Whether subtle impairments in functional or social abilities at the CIND stage can predict progression to AD is not yet fully determined. We evaluated whether impairments on the Disability Assessment for Dementia (DAD) and Functional Rating Scale (FRS) can predict progression to AD. METHODS: We examined 70 patients with CIND from the ACCORD cohort having complete DAD and FRS baseline and 2-year follow-up data. MANCOVA adjusted for age, sex, education and baseline MMSE score compared the baseline and 2-year change in DAD and FRS scores in CIND patients who progressed to AD versus non-progressors. RESULTS: There were no significant differences between CIND progressors and non-progressors in baseline total DAD or FRS scores. FRS domain analysis revealed that greater impairment in social/occupational functioning significantly predicted progression, while there were no predictive DAD domains. In progressors, both DAD and FRS scores significantly declined over time with the largest changes in instrumental activities of daily living (IADL). CONCLUSION: While changes in IADL characterize the progression from CIND to AD, impairment in complex social-cognitive competency significantly predicts risk of progression and may mark early AD. [ABSTRACT FROM AUTHOR]

Background: Depressive symptoms of varying severity are prevalent in up to 63% of Alzheimer disease (AD) patients and often result in greater cognitive decline and increased caregiver burden. The current study aimed to determine the neural correlates of depressive symptoms in a sample of AD patients. Methods: Using the Cornell Scale for Depression in Dementia, we assessed 56 patients who met criteria for probable AD. Data obtained from Technetium-99m ethyl cysteinate dimer single photon emission computed tomography (SPECT) were analyzed with the use of a magnetic resonance imagingDSderived region of interest (ROI) anatomic template before and after atrophy correction and statistical parametric mapping (SPM). The following 4 frontal ROIs were investigated bilaterally: middle frontal gyrus (Brodmann's area [BA] 46), orbitofrontal cortex (BA 11), superior prefrontal (BA 8/9) and anterior cingulate (BA 24/25/32/33). Results: Depressive symptoms were present in 27 of the AD patients (48%). Patients with depressive symptoms showed less perfusion in the right superior and bilateral middle frontal gyri (p < 0.005), left superior frontal (p < 0.05) and anterior cingulate gyri (p < 0.005) before atrophy correction. SPM analyses revealed significantly lower perfusion in bilateral dorsolateral and superior prefrontal cortex of patients with depressive symptoms (right, p < 0.005; left, p < 0.05). SPECT ROI analyses with atrophy correction revealed trends similar to data without atrophy correction but did not reach statistical significance. Conclusion: In this study, depressive symptoms in AD patients were associated with relative hypoperfusion in the prefrontal cortex when they were compared with AD patients without depressive symptoms. These findings are consistent with previous reports in studies of primary depression suggesting that these regions are involved in affect and emotional regulation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Previous research has shown that cognitively-impaired-not-demented (CIND) individuals with at least one neuropsychiatric symptom (NPS) have more functional disability than individuals without any NPSs. The objectives of the present study were to determine whether there are consistent clusters of NPS in CIND individuals and whether certain NPS clusters are more strongly associated with measures of functional disability than other NPS clusters in this population. METHODS: This was a cross-sectional baseline study of NPS using the Neuropsychiatric Inventory (NPI) in a national clinic-based observational cohort study (the Canadian Cohort Study of Cognitive Impairment and Related Dementias study). The present investigation focuses on a subset of CIND subjects (73%) whose informant endorsed the presence of at least one NPI item. RESULTS: A hierarchical cluster analysis identified two NPS clusters. One consisted of mood factors (i.e., depression, anxiety, apathy, irritability, and problems with sleep) and the other cluster captured frontal symptoms (i.e., aberrant motor behavior, disinhibition, agitation, and problems with appetite). NPSs grouped within the mood cluster were more common than the frontal cluster (95% of subjects had at least one NPS within the mood cluster versus 53% in the frontal cluster). However, the frontal cluster was more strongly associated with functional disability measures even after controlling for cognitive status (i.e., the Mini-Mental State Exam) and the mood cluster score. CONCLUSION: The frontal cluster of NPSs was more strongly associated with functional disability than the mood cluster. [ABSTRACT FROM AUTHOR]

Background/Aims: To investigate relationships between subcortical hyperintensities (SH), frontal perfusion and executive function (EF) in a sample of Alzheimer's disease (AD) patients with varying severities of SH. Methods: A sample of 63 AD patients underwent brain imaging with magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) scans. Severity of SH was assessed using a standardized visual rating scale on MRI. Patients were classified into severe (n = 20), moderate (n = 23) or no SH (n = 20) groups. Four frontal SPECT regions of interest (anterior cingulate cortex, dorsolateral prefrontal cortex) and neuropsychological assessment of EF were analyzed. Results: Overall, no significant relationships were found between severity of SH and measures of SPECT perfusion or EF, except for one subsection of the Dementia Rating Scale, with severe SH scoring slightly worse than the other two groups. Conclusion: These findings support previous studies which suggest minimal adverse effects of SH on brain function and cognition. Global severity of SH on MRI in AD was not associated with decline in frontal perfusion and only mildly related to a decline in a specific EF task. More accurate measures of SH volume, not just global severity of SH, may be necessary to capture such complex brain behavior relationships; if they do indeed exist. Copyright (c) 2007 S. Karger AG, Basel. [ABSTRACT FROM AUTHOR]

BACKGROUND/AIMS: Fronto-temporal dementia (FTD) designates a group of relatively common neurodegenerative disorders. The aim of this study was to characterize the patterns of brain atrophy in FTD compared to Alzheimer's disease (AD). METHODS: A novel semiautomatic volumetric MRI analysis method was applied to measure regional brain volumes in FTD (n = 15; behavioural variant n = 9, language variant n = 6) in contrast with AD patients (n = 15) and age-matched controls (NC) (n = 15). FTD and AD patients were matched on demographic measures and Mini Mental State Examination scores. RESULTS: Significant atrophy was present in the frontal and anterior temporal lobes of subjects with FTD compared to AD (p = 0.02; effect size = 1.11) and compared to NC (p < 0.001; effect size = 1.86). Severe atrophy of the left anterior temporal region distinguished the language variant. AD patients, by contrast, did not differ from NC for frontal lobe volume but had smaller anterior temporal lobes (p = 0.03). Both dementia groups had medial temporal lobe atrophy of similar magnitude. A logistic regression model including 4 regional measures correctly classified 100% of subjects. CONCLUSION: FTD can be reliably differentiated from AD by virtue of a topographical pattern of atrophy involving the frontal lobes and anterior temporal regions. Medial temporal lobe volumes do not distinguish FTD from AD. [ABSTRACT FROM AUTHOR]

Intravenous tissue plasminogen activator (tPA) is standard treatment for eligible patients with acute ischemic stroke, but may be less effective for very severe strokes caused by proximal intracranial artery occlusions. We report the case of a woman with a devastating stroke who recovered completely following emergency revascularization of an occluded proximal middle cerebral artery using a novel treatment approach that combines both intravenous (IV) and intra-arterial (IA) tPA. This case illustrates the potential value of the combined IV-IA thrombolytic approach, which is an emerging investigational treatment strategy for selected patients with severe acute ischemic stroke. [ABSTRACT FROM AUTHOR]