A Cost-Benefit Analysis of a Group Memory Intervention for Healthy Older Adults with Memory Concerns.

This study examines whether memory intervention programs can mitigate health care costs. Research suggests these programs translate to a decreased intention of older adults who are worried about age-normal memory changes to seek traditional outlets for medical/psychiatric help. We employed a cost-benefit analysis approach to analyze the effectiveness of a memory intervention program within Ontario. We leveraged estimates of decreased intentionality to seek physician care following a community-based memory intervention with physician billing profiles to calculate the potential cost savings to the province's health care system. The intervention studied was found to reduce provincial health care spending by $6,094 per program group. This amount exceeds $121.25 in direct costs per attendee associated with administering five program sessions. This analysis justifies further research on how community-based memory and aging programs can offer low-cost solutions to help individuals cope with subjective memory complaints and assist the health care system in prioritizing care for aging patients.

Protocol for live-cell imaging during Tumor Treating Fields treatment with Inovitro Live.

Tumor Treating Fields (TTFields) are an FDA-approved anticancer treatment using alternating electric fields. Here, we present a protocol to perform live-cell imaging (LCI) of cells during TTFields treatment with the Inovitro LiveTM system. The setup we describe dissipates TTFields-related heat production and can be used in conjunction with any LCI-compatible microscope setup. This approach will enable further elucidation of TTFields' mechanism of action at the molecular level and facilitate the development of promising combination strategies.

Functional Connectivity Between the Posterior Default Mode Network and Parahippocampal Gyrus Is Disrupted in Older Adults with Subjective Cognitive Decline and Correlates with Subjective Memory Ability.

BACKGROUND: Subjective cognitive decline (SCD) is associated with increased risk of developing Alzheimer's disease (AD). However, the underlying mechanisms for this association remain unclear. Neuroimaging studies suggest the earliest AD-related changes are large-scale network disruptions, beginning in the posterior default mode (pDMN) network. OBJECTIVE: To examine the association between SCD and pDMN network connectivity with medial temporal lobe (MTL) regions using resting-state functional magnetic resonance imaging. METHODS: Forty-nine participants with either SCD (n = 23, 12 females; mean age: 70.7 (5.5)) or who were cognitively unimpaired (CU; n = 26, 16 females, mean age: 71.42 (7.3)) completed the Memory Functioning Questionnaire, a measure of subjective memory, and underwent resting state functional MRI at 3 Tesla. Functional connectivity between the posterior cingulate cortex (PCC), as the key pDMN node, and MTL regions were compared between SCD and CU groups. Further, the association between pDMN-MTL connectivity and the Frequency of Forgetting subscale of the Memory Functioning Questionnaire was examined. RESULTS: Connectivity between the PCC-MTL was observed in the CU group but was absent in SCD (t(47) = 2.69, p = 0.01). Across all participants, self-perception of frequency of forgetting, but not objective memory, was strongly correlated with connectivity between the PCC-left parahippocampal gyrus (r = 0.43, p = 0.002). CONCLUSION: These findings support the hypothesis that increased AD risk in SCD may be mediated by disrupted pDMN-parahippocampal connectivity. In addition, these findings suggest that frequency of forgetting may serve as a potential biomarker of SCD due to incipient AD.

Structural Brain Magnetic Resonance Imaging to Rule Out Comorbid Pathology in the Assessment of Alzheimer's Disease Dementia: Findings from the Ontario Neurodegenerative Disease Research Initiative (ONDRI) Study and Clinical Trials Over the Past 10 Years.

BACKGROUND/OBJECTIVE: Structural brain magnetic resonance imaging (MRI) is not mandatory in Alzheimer's disease (AD) research or clinical guidelines. We aimed to explore the use of structural brain MRI in AD/mild cognitive impairment (MCI) trials over the past 10 years and determine the frequency with which inclusion of standardized structural MRI acquisitions detects comorbid vascular and non-vascular pathologies. METHODS: We systematically searched ClinicalTrials.gov for AD clinical trials to determine their neuroimaging criteria and then used data from an AD/MCI cohort who underwent standardized MRI protocols, to determine type and incidence of clinically relevant comorbid pathologies. RESULTS: Of 210 AD clinical trials, 105 (50%) included structural brain imaging in their eligibility criteria. Only 58 (27.6%) required MRI. 16,479 of 53,755 (30.7%) AD participants were in trials requiring MRI. In the observational AD/MCI cohort, 141 patients met clinical criteria; 22 (15.6%) had relevant MRI findings, of which 15 (10.6%) were exclusionary for the study. DISCUSSION: In AD clinical trials over the last 10 years, over two-thirds of participants could have been enrolled without brain MRI and half without even a brain CT. In a study sample, relevant comorbid pathology was found in 15% of participants, despite careful screening. Standardized structural MRI should be incorporated into NIA-AA diagnostic guidelines (when available) and research frameworks routinely to reduce diagnostic heterogeneity.

Agitation, Oxidative Stress, and Cytokines in Alzheimer Disease: Biomarker Analyses From a Clinical Trial With Nabilone for Agitation.

The endocannabinoid system has been a target of interest for agitation in Alzheimer disease (AD) because of potential behavioral effects and its potential impact on mechanisms implicated in AD such as oxidative stress (OS) and neuroinflammation. We explored whether serum markers of OS and neuroinflammation were associated with response to the cannabinoid nabilone in agitated patients with AD (N = 38). All participants were enrolled in a 14-week, double-blind, cross-over trial comparing nabilone to placebo (6 weeks each) with a 1-week washout between phases. Samples were collected at the start and end of each phase. The cross-sectional relationship agitation (Cohen Mansfield Agitation Inventory) and OS and inflammatory markers were investigated to select markers of interest. Significant markers were then explored for their relationship with response. The OS marker, 4-hydroxynonenal (4-HNE; F1, 35 = 6.41, P = .016), and the proinflammatory cytokine, tumor necrosis factor-α (TNF-α; F1, 29 = 3.97, P = .06), were associated with agitation severity, and TNF-α remained significantly associated (F2, 25 = 3.69, P = .04) after adjustment for cognition. In the placebo phase, lower baseline 4-HNE was associated with decreases in agitation severity only (b = 0.01, P = .01), while lower baseline TNF-α was associated with decreases in agitation severity in the nabilone phase only (b = 1.14, P = .045). Changes in 4-HNE were not associated with changes in agitation severity in either phase. In the nabilone phase, lower baseline TNF-α was associated with decreases in agitation severity (b = 1.14, P = .045), and decreases in TNF-α were associated with decreases in agitation severity (b = 1.12, P = .006). These findings suggest that OS and neuroinflammation may be associated with agitation severity, while nabilone may have anti-inflammatory effects.

Prefrontal GABA Levels Correlate with Memory in Older Adults at High Risk for Alzheimer's Disease.

γ-Aminobutyric acid (GABA), a primary inhibitory neurotransmitter in the brain, plays a significant role in aging and in neurodegenerative disorders, including Alzheimer's disease (AD). We investigated the relationship between GABA levels in the dorsomedial/dorsoanterolateral prefrontal cortex (DM/DA-PFC) and memory in high-AD risk participants. Thirty-eight participants (14 Cognitively Normal [CN], 11 with Subjective Cognitive Decline (SCD), and 13 Mild Cognitive Impairment [MCI]) underwent magnetic resonance spectroscopy at 3 Tesla. SCD and MCI participants were grouped together to form a single high-AD risk group (N = 24) for the purposes of statistical analyses. Partial correlations of GABA+/Cr level with verbal memory, assessed on California Verbal Learning Test-II, and nonverbal memory, assessed on Brief Visuospatial Memory Test and Rey-Osterrieth test, were examined separately within the high-AD risk and CN groups. GABA+/Cr levels were positively correlated with long-delayed verbal memory (r = 0.69, P = 0.009) and immediate nonverbal memory (r = 0.97, P = 0.03) in high-AD risk, but not in CN participants. These results remained significant after controlling for depression. These preliminary findings, which require replication due to the limited sample sizes, are the first report of an association between GABA+/Cr levels within the DM/DA-PFC and memory performance in high-AD risk individuals.

Cerebrovascular Pulsatility During Rest and Exercise Reflects Hemodynamic Impairment in Stroke and Cerebral Small Vessel Disease.

Although aerobic exercise is recommended as a core component of stroke rehabilitation, knowledge of acute cerebrovascular responses in patients is limited. This study tested the hypothesis that older adults with chronic stroke or cerebral small vessel disease (SVD) exhibit a greater increase in pulsatile hemodynamics during exercise compared with young and age-matched healthy adults. Middle cerebral artery blood flow velocity was acquired during 20 min of moderate intensity cycling in 51 participants from four groups (young, old, SVD and stroke). During rest, only the stroke group had a higher pulsatility index (PI) compared with the young group (1.02 ± 0.17 vs 0.83 ± 0.13; p = 0.038). During exercise, however, the SVD group exhibited a larger increase in PI (68 ± 20% relative to rest) than the young (47 ± 19%), old (45 ± 17%) and stroke (40 ± 25%) groups (p < 0.05, for each). The stress of aerobic exercise may reveal arterial dysfunction associated with latent and overt cerebrovascular disease.

Investigating the safety and efficacy of nabilone for the treatment of agitation in patients with moderate-to-severe Alzheimer's disease: Study protocol for a cross-over randomized controlled trial.

Agitation is a prevalent and difficult-to-treat symptom in patients with moderate-to-severe Alzheimer's disease (AD). Though there are nonpharmacological and pharmacological interventions recommended for the treatment of agitation, the efficacy of these are modest and not always consistent. Furthermore, the safety profiles of currently prescribed medications are questionable. Nabilone, a synthetic cannabinoid, has a distinct pharmacological profile that may provide a safer and more effective treatment for agitation, while potentially having benefits for weight and pain. Additionally, emerging evidence suggests nabilone may have neuroprotective effects. We describe a clinical trial investigating the safety and efficacy of nabilone for the treatment of agitation in patients with moderate-to-severe AD. This will be a double-blind, randomized cross-over study comparing 6 weeks of nabilone (0.5-2 mg) and placebo, with a 1-week washout preceding each phase. Study outcomes will be measured at baseline and end of treatment for each treatment phase. The primary outcome measure will be agitation as assessed by the Cohen-Mansfield Agitation Inventory. The secondary outcomes include safety, behaviour (Neuropsychiatric Inventory), cognition (standardized Mini Mental Status Exam and either Severe Impairment Battery or Alzheimer's disease Assessment Scale-Cognitive subscale) and global impression (Clinician's Global Impression of Change). Exploratory outcomes include pain (Pain Assessment in Advanced AD), nutritional status (Mini-Nutritional Assessment-Short Form), caregiver distress (NPI caregiver distress), and blood-based biomarkers. A safe and efficacious pharmacological intervention for agitation, with effects on pain and weight loss in patients with moderate-to-severe AD could increase quality-of-life, reduce caregiver stress and avoid unnecessary institutionalization and related increases in health care costs. CLINICAL TRIALS NUMBER: NCT02351882.

24S-Hydroxycholesterol Is Associated with Agitation Severity in Patients with Moderate-to-Severe Alzheimer's Disease: Analyses from a Clinical Trial with Nabilone.

BACKGROUND: Agitation is a prevalent and difficult-to-treat symptom of Alzheimer's disease (AD). The endocannabinoid system (ECS) has been a target of interest for the treatment of agitation. However, ECS signaling may interact with AD-related changes in brain cholesterol metabolism. Elevated brain cholesterol, reflected by reduced serum 24-S-hydroxycholesterol (24S-OHC), is associated with reduced membrane fluidity, preventing ligand binding to cannabinoid receptor 1. OBJECTIVE: To assess whether 24S-OHC was associated with agitation severity and response to nabilone. METHODS: 24S-OHC was collected from AD patients enrolled in a clinical trial on nabilone at the start and end of each phase. This allowed for the cross-sectional and longitudinal investigation between 24S-OHC and agitation (Cohen Mansfield Agitation Inventory, CMAI). Post-hoc analyses included adjustments for baseline standardized Mini-Mental Status Exam (sMMSE), and analyses with CMAI subtotals consistent with the International Psychogeriatric Association (IPA) definition for agitation (physical aggression and nonaggression, and verbal aggression). RESULTS: 24S-OHC was not associated with CMAI scores cross-sectionally or longitudinally, before and after adjusting for baseline sMMSE. However, 24S-OHC was associated with greater CMAI IPA scores at baseline (F(1,36) = 4.95, p = 0.03). In the placebo phase only, lower 24S-OHC at baseline was associated with increases in CMAI IPA scores (b = -35.2, 95% CI -65.6 to -5.0, p = 0.02), and decreases in 24S-OHC were associated with increases in CMAI IPA scores (b = -20.94, 95% CI -57.9 to -4.01, p = 0.03). CONCLUSION: 24S-OHC was associated with agitation severity cross-sectionally, and longitudinally in patients with AD. However, 24S-OHC did not predict treatment response, and does not change over time with nabilone.

Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer's Disease.

OBJECTIVE: To investigate the efficacy and safety of nabilone for agitation in patients with moderate-to-severe Alzheimer's disease (AD). DESIGN: This 14-week randomized double-blind crossover trial compared nabilone to placebo (6 weeks each) with a 1-week washout between phases. SETTING: Patients were recruited from a long-term care facility and geriatric psychiatry clinics. PARTICIPANTS: Patients had AD (standardized Mini-Mental State Examination [sMMSE ≤24]) and agitation (Neuropsychiatric Inventory-Nursing Home version [NPI-NH]-agitation/aggression subscore ≥3). INTERVENTION: Nabilone (target 1-2 mg) versus placebo. MEASUREMENTS: The primary outcome was agitation (Cohen Mansfield Agitation Inventory [CMAI]). Secondary outcomes included NPI-NH total, NPI-NH caregiver distress, cognition (sMMSE and Severe Impairment Battery [SIB] or Alzheimer's Disease Assessment Scale of Cognition), global impression (Clinician's Global Impression of Change [CGIC]), and adverse events. RESULTS: Thirty-nine patients (mean ± SD age = 87 ± 10, sMMSE = 6.5 ± 6.8, CMAI = 67.9 ± 17.6, NPI-NH total = 34.3 ± 15.8, 77% male, nabilone dose = 1.6 ± 0.5 mg) were randomized. There were no crossover or treatment-order effects. Using a linear mixed model, treatment differences (95% CI) in CMAI (b = -4.0 [-6.5 to -1.5], t(30.2) = -3.3, p = 0.003), NPI-NH total (b = -4.6 [-7.5 to -1.6], t(32.9) = -3.1, p = 0.004), NPI-NH caregiver distress (b = -1.7 [-3.4 to -0.07, t(33.7) = -2.1, p = 0.041), and sMMSE (b = 1.1 [0.1-2.0], t(22.6) = 2.4, p = 0.026) all favored nabilone. However, in those who completed the SIB (n = 25) treatment differences favored placebo (b = -4.6 [-7.3 to -1.8], t(20.7) = -4.8, p = 0.003). CGIC improvement during nabilone (47%) and placebo (23%) was not significantly different (McNemar's test, exact p = 0.09). There was more sedation during nabilone (45%) compared to placebo (16%) phases (McNemar's test, exact p = 0.02), but treatment-limiting sedation was not significantly different (McNemar's test, exact p = 0.22). CONCLUSIONS: Nabilone may be an effective treatment for agitation. However, sedation and cognition should be closely monitored.

Mycobacterium branderi Infection in a Horse with Granulomatous Mesenteric Lymphadenitis.

Although relatively uncommon in horses, infections caused by Mycobacterium spp. may affect the gastrointestinal tract. Mycobacterium branderi is a non-tuberculous Mycobacterium (NTM) that causes respiratory infections in man. Non-tuberculous mycobacteria may also affect horses; however, infection by M. branderi has not yet been reported in this species. This report describes the clinical, pathological, microbiological and molecular findings of M. branderi infection in a horse, causing granulomatous mesenteric lymphadenitis. A 17-year-old Thoroughbred stallion had a 3-month history of chronic diarrhoea, cachexia and ventral and cervical oedema. Necropsy examination revealed severe mesenteric lymphadenomegaly, together with mesenteric lymphangiectasia and diffuse small intestinal mucosal thickening. Microscopically, the mesenteric lymph node had diffuse granulomatous inflammatory infiltration, replacing most of the nodal parenchyma, with multiple acid-fast bacilli within the cytoplasm of macrophages. There was also diffuse lymphangiectasia. Fresh samples of mesenteric lymph nodes yielded no bacterial growth; however, nested polymerase chain reaction products obtained from the mesenteric lymph node samples were consistent with M. branderi. This infection should be included as a differential diagnosis in cases of chronic diarrhoea in horses, especially when granulomatous enteritis and lymphadenitis are also observed.

Association between Sleep Disturbances and Medial Temporal Lobe Volume in Older Adults with Mild Cognitive Impairment Free of Lifetime History of Depression.

BACKGROUND: Previous studies examining the link between neuropsychiatric symptoms (NPS) and biomarkers of Alzheimer's disease (AD) may be confounded by remitted or past history of psychiatric illness, which in itself is associated with AD biomarkers such as reduced medial temporal lobe (MTL) volume. OBJECTIVE: We examined associations between mood and anxiety-related NPS and MTL in older adults with mild cognitive impairment (MCI) free of lifetime history of depression. We hypothesized an inverse relationship between NPS severity and MTL. METHODS: Forty-two MCI participants without current or past history of depression or other major psychiatric illness were assessed using the Neuropsychiatric Inventory-Questionnaire (NPI-Q). Correlation and regression analyses were performed between selected NPI-Q items and regional MTL volumes from structural magnetic resonance imaging. RESULTS: Sleep disturbances were inversely associated with several regional volumes within the MTL. Sleep disturbances remained significantly correlated with left hippocampal and amygdala volume following correction for multiple comparisons. In contrast, depression and anxiety were not correlated with MTL. CONCLUSIONS: The relationship between reduced MTL and sleep, but not with depressed or anxious states, in MCI free of lifetime history of depression, suggests a potential mechanism for sleep as a risk factor for AD. The current findings highlight the importance of accounting for remitted psychiatric conditions in studies of the link between NPS and AD biomarkers and support the need for further research on sleep as clinical biomarker of AD and target for AD prevention.

Identification of MEK162 as a Radiosensitizer for the Treatment of Glioblastoma.

Glioblastoma (GBM) is a highly aggressive and lethal brain cancer type. PI3K and MAPK inhibitors have been studied preclinically in GBM as monotherapy, but not in combination with radiotherapy, which is a key component of the current standard treatment of GBM. In our study, GBM cell lines and patient representative primary cultures were grown as multicellular spheroids. Spheroids were treated with a panel of small-molecule drugs including MK2206, RAD001, BEZ235, MLN0128, and MEK162, alone and in combination with irradiation. Following treatment, spheroid growth parameters (growth rate, volume reduction, and time to regrow), cell-cycle distribution and expression of key target proteins were evaluated. In vivo, the effect of irradiation (3 × 2 Gy) without or with MEK162 (50 mg/kg) was studied in orthotopic GBM8 brain tumor xenografts with endpoints tumor growth and animal survival. The MAPK-targeting agent MEK162 was found to enhance the effect of irradiation as demonstrated by growth inhibition of spheroids. MEK162 downregulated and dephosphorylated the cell-cycle checkpoint proteins CDK1/CDK2/WEE1 and DNA damage response proteins p-ATM/p-CHK2. When combined with radiation, this led to a prolonged DNA damage signal. In vivo data on tumor-bearing animals demonstrated a significantly reduced growth rate, increased growth delay, and prolonged survival time. In addition, RNA expression of responsive cell cultures correlated to mesenchymal stratification of patient expression data. In conclusion, the MAPK inhibitor MEK162 was identified as a radiosensitizer in GBM spheroids in vitro and in orthotopic GBM xenografts in vivo The data are supportive for implementation of this targeted agent in an early-phase clinical study in GBM patients. Mol Cancer Ther; 17(2); 347-54. ©2017 AACRSee all articles in this MCT Focus section, "Developmental Therapeutics in Radiation Oncology."

Negative Emotional Verbal Memory Biases in Mild Cognitive Impairment and Late-Onset Depression.

OBJECTIVE: Early and preferential targeting of limbic structures by Alzheimer disease (AD)-related pathology suggests emotion dysregulation may serve as a marker of AD risk. We studied emotional verbal memory in two groups at risk for AD, amnestic mild cognitive impairment (aMCI) and late-onset depression (LOD), to test the hypothesis that aMCI and LOD would be characterized by a negative bias in emotional memory, whereas cognitively normal (CN) adults would show the "positivity effect" associated with healthy aging. METHODS: Participants completed a novel test of emotional verbal memory, the Emotional Verbal Learning Test (EVeLT), consisting of a 15-item list of words with positive, negative, or neutral valence. Recall as a function of group and valence was analyzed using mixed analysis of variance. Spearman's rho was used to examine associations between EVeLT, mood, and executive function. MCI and CN participants had no current or past history of mood or anxiety disorders. aMCI participants met neuropsychological criteria for single-domain aMCI (sd-aMCI). LOD developed their first episode of depression at ≥60 years of age. RESULTS: CN adults recalled more positive words, whereas sd-aMCI and LOD adults recalled more negative, relative to neutral, words on the EVeLT. Positive emotional memory and negative attitudes regarding self were inversely correlated in CN adults. CONCLUSION: sd-aMCI and LOD groups show negative emotional memory biases, consistent with our hypothesis that emotion dysregulation is a signature of AD risk.

Quantitative imaging of neuroinflammation in human white matter: a positron emission tomography study with translocator protein 18 kDa radioligand, [18F]-FEPPA.

The ability to quantify translocator protein 18 kDa (TSPO) in white matter (WM) is important to understand the role of neuroinflammation in neurological disorders with WM involvement. This article aims to extend the utility of TSPO imaging in WM using a second-generation radioligand, [18F]-FEPPA, and high-resolution research tomograph (HRRT) positron emission tomography (PET) camera system. Four WM regions of interests (WM-ROI), relevant to the study of aging and neuroinflammatory diseases, were examined. The corpus callosum, cingulum bundle, superior longitudinal fasciculus, and posterior limb of internal capsule were delineated automatically onto subject's T1 -weighted magnetic resonance image using a diffusion tensor imaging-based WM template. The TSPO polymorphism (rs6971) stratified individuals to three genetic groups: high-affinity binders (HAB), mixed-affinity binders (MAB), and low-affinity binders. [18F]-FEPPA PET scans were acquired on 32 healthy subjects and analyzed using a full kinetic compartment analysis. The two-tissue compartment model showed moderate identifiability (coefficient of variation 15-19%) for [18F]-FEPPA total volume distribution (VT ) in WM-ROIs. Noise affects VT variability, although its effect on bias was small (6%). In a worst-case scenario, ≤6% of simulated data did not fit reliably. A simulation of increased TSPO density exposed minimal effect on variability and identifiability of [18F]-FEPPA VT in WM-ROIs. We found no association between age and [18F]-FEPPA VT in WM-ROIs. The VT values were 15% higher in HAB than in MAB, although the difference was not statistically significant. This study provides evidence for the utility and limitations of [18F]-FEPPA PET to measure TSPO expression in WM.

The assessment of spatial distribution of soil salinity risk using neural network.

Soil salinity in the Aral Sea Basin is one of the major limiting factors of sustainable crop production. Leaching of the salts before planting season is usually a prerequisite for crop establishment and predetermined water amounts are applied uniformly to fields often without discerning salinity levels. The use of predetermined water amounts for leaching perhaps partly emanate from the inability of conventional soil salinity surveys (based on collection of soil samples, laboratory analyses) to generate timely and high-resolution salinity maps. This paper has an objective to estimate the spatial distribution of soil salinity based on readily or cheaply obtainable environmental parameters (terrain indices, remote sensing data, distance to drains, and long-term groundwater observation data) using a neural network model. The farm-scale (∼15 km(2)) results were used to upscale soil salinity to a district area (∼300 km(2)). The use of environmental attributes and soil salinity relationships to upscale the spatial distribution of soil salinity from farm to district scale resulted in the estimation of essentially similar average soil salinity values (estimated 0.94 vs. 1.04 dS m(-1)). Visual comparison of the maps suggests that the estimated map had soil salinity that was uniform in distribution. The upscaling proved to be satisfactory; depending on critical salinity threshold values, around 70-90% of locations were correctly estimated.

Nitrogen fixation by Elaeagnus angustifolia in the reclamation of degraded croplands of Central Asia.

Extensive degradation of irrigated croplands, due to increasing soil salinity and depletion of soil nutrient stocks, is a major problem in Central Asia (CA), one of the largest irrigated areas in the world. To assess the potential for improving the productive capacity of degraded lands by afforestation, we examined N(2) fixation of Elaeagnus angustifolia L. in mixed plantations with non-fixing Populus euphratica Oliv. and Ulmus pumila L. Fixation of N(2) was quantified by the (15)N natural abundance technique based on both foliar and whole-plant sampling during five consecutive growing seasons. Despite elevated root-zone soil salinity (6-10 dS m(-1)) and deficiency in plant-available P (4-15 mg kg(-1)), N(2) fixation (%Ndfa) increased from an initial value of 20% to almost 100% over 5 years. Within each growing season, %Ndfa steadily increased and peaked in the fall. Annual N(2) fixation, determined using foliar delta(15)N, initially averaged 0.02 Mg ha(-1), peaked at 0.5 Mg ha(-1) during the next 2 years and thereafter stabilized at 0.3 Mg ha(-1). Estimates based on whole-plant delta(15)N were <10% lower than those based on foliar delta(15)N. The increase in plant-available soil N was significantly higher in E. angustifolia plots than in P. euphratica and U. pumila plots. Increases in the concentrations of organic C (19%), total N (21%) and plant-available P (74%) in the soil were significant irrespective of tree species. This improvement in soil fertility is further evidence that afforestation with mixed-species plantations can be a sustainable land use option for the degraded irrigated croplands in CA.

A positron emission tomography study of 5-hydroxytryptamine-1A receptors in Alzheimer disease.

OBJECTIVE: The important role of serotonin-1A (5-hydroxytryptamine-1A [5-HT(1A)]) receptors in cognition, behavior, and drug response is increasingly being recognized. Postmortem studies suggest decreased 5-HT(1A) receptors in patients with Alzheimer disease (AD), but this has not been confirmed in vivo. Our primary objective was to assess the extent of 5-HT(1A) receptor losses in mild to moderate AD. METHODS: The authors examined 5-HT(1A) receptors in 10 patients with mild to moderate AD and 10 healthy volunteers with the same sex and similar age using positron emission tomography imaging with the selective 5-HT(1A) receptor radioligand, [(11)C]WAY-100635. Regions of interest (ROIs) were manually drawn on coregistered magnetic resonance images for the frontal, lateral temporal, medial temporal (MTC), parietal, and cerebellar cortices. Using the simplified reference tissue model, 5-HT(1A) binding potentials (BPs) were calculated relative to the cerebellum. RESULTS: After adjusting for partial volume effects, ROI analysis showed a significant group effect (AD versus comparison group) on BP. Analysis of between-subjects factors showed significantly decreased 5-HT(1A) BP in the right MTC, but not in the other ROIs. CONCLUSION: Given the strategic role of these receptors, loss of right medial temporal 5-HT(1A) receptors might play an important role in AD symptomatology.