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1.  A consecutive case series experience with [18 F] florbetapir PET imaging in an urban dementia center: impact on quality of life, decision making, and disposition 
Background
Identification and quantification of fibrillar amyloid in brain using positron emission tomography (PET) imaging and Amyvid™ ([18 F] Amyvid, [18 F] florbetapir, 18 F-AV-45) was recently approved by the US Food and Drug Administration as a clinical tool to estimate brain amyloid burden in patients being evaluated for cognitive impairment or dementia. Imaging with [18 F] florbetapir offers in vivo confirmation of the presence of cerebral amyloidosis and may increase the accuracy of the diagnosis and likely cause of cognitive impairment (CI) or dementia. Most importantly, amyloid imaging may improve certainty of etiology in situations where the differential diagnosis cannot be resolved on the basis of standard clinical and laboratory criteria.
Results
A consecutive case series of 30 patients (age 50-89; 16 M/14 F) were clinically evaluated at a cognitive evaluation center of urban dementia center and referred for [18 F] florbetapir PET imaging as part of a comprehensive dementia workup. Evaluation included neurological examination and neuropsychological assessment by dementia experts. [18 F] florbetapir PET scans were read by trained nuclear medicine physicians using the qualitative binary approach. Scans were rated as either positive or negative for the presence of cerebral amyloidosis. In addition to a comprehensive dementia evaluation, post [18 F] florbetapir PET imaging results caused diagnoses to be changed in 10 patients and clarified in 9 patients. Four patients presenting with SCI were negative for amyloidosis. These results show that [18 F] florbetapir PET imaging added diagnostic clarification and discrimination in over half of the patients evaluated.
Conclusions
Amyloid imaging provided novel and essential data that: (1) caused diagnosis to be revised; and/or (2) prevented the initiation of incorrect or suboptimal treatment; and/or (3) avoided inappropriate referral to an anti-amyloid clinical trial.
doi:10.1186/1750-1326-9-10
PMCID: PMC3913628  PMID: 24484858
Amyvid™; Florbetapir; PET; Clinical series; Alzheimer’s disease; Neuroimaging
2.  Functional Neural Correlates of Attentional Deficits in Amnestic Mild Cognitive Impairment 
PLoS ONE  2013;8(1):e54035.
Although amnestic mild cognitive impairment (aMCI; often considered a prodromal phase of Alzheimer’s disease, AD) is most recognized by its implications for decline in memory function, research suggests that deficits in attention are present early in aMCI and may be predictive of progression to AD. The present study used functional magnetic resonance imaging to examine differences in the brain during the attention network test between 8 individuals with aMCI and 8 neurologically healthy, demographically matched controls. While there were no significant behavioral differences between groups for the alerting and orienting functions, patients with aMCI showed more activity in neural regions typically associated with the networks subserving these functions (e.g., temporoparietal junction and posterior parietal regions, respectively). More importantly, there were both behavioral (i.e., greater conflict effect) and corresponding neural deficits in executive control (e.g., less activation in the prefrontal and anterior cingulate cortices). Although based on a small number of patients, our findings suggest that deficits of attention, especially the executive control of attention, may significantly contribute to the behavioral and cognitive deficits of aMCI.
doi:10.1371/journal.pone.0054035
PMCID: PMC3543395  PMID: 23326568
3.  Evaluating cognition in an elderly cohort via telephone assessment 
Objective
Longitudinal neuropsychological assessment provides the opportunity to observe the earliest transition to cognitive impairment in healthy, elderly individuals. We examined the feasibility, and its comparability to in-person assessment, of a telephone administered battery of established neuropsychological measures of cognitive functioning in healthy, elderly women.
Methods
Fifty-four women (age = 79 ± 7.7; education = 15.4 ± 3.3) who were in self-reported good health were recruited from senior centers and other community sources. A two-way cross-over design was used in which participants were randomly assigned to receive either (1) in-person neuropsychological assessment followed by telephone assessment and (2) telephone assessment followed by in-person assessment, separated by approximately 4 weeks. Linear regression models were used to determine whether there were performance differences by method (in-person vs. telephone), and equivalence testing assessed comparability of the two methods.
Results
There were no statistically significant differences in performance between in-person and telephone assessments on most neuropsychological tests, with the exception of digit span backward, Oral Trail Making Test Part A, and delayed recall on the SRT, the latter likely related to non-comparable exposure (6-trials in-person vs. 3-trials telephone). Equivalence testing differences fell in the pre-specified clinical equivalence zones, providing evidence of comparability of the two methods.
Conclusions
These pilot data support telephone administration of a neuropsychological battery that yields comparable performance to in-person assessment with respect to most instruments. Significant differences in scores on some measures suggest care should be taken in selecting specific measures used in a neuropsychological battery administered by telephone.
doi:10.1002/gps.2373
PMCID: PMC3526377  PMID: 19697298
telephone assessment; aging; cognition
4.  Age-related decline in nicotinic receptor availability with [123I]5-IA-85380 SPECT 
Neurobiology of aging  2008;30(9):1490-1497.
Human postmortem studies have reported decreases with age in high affinity nicotine binding in brain. We investigated the effect of age on β2-containing nicotinic acetylcholine receptor (β2-nAChR) availability in eight brain regions of living human subjects using the ligand [123I]5-IA-85380 ([123I]5-IA) and single photon emission computed tomography (SPECT). Healthy, nonsmokers (N=47) ranging in age from 18-85 were administered [123I]5-IA using a bolus plus constant infusion paradigm and imaged 6-8 h later under equilibrium conditions. The effect of age on regional β2-nAChR availability (VT, regional brain activity/free plasma parent, a measure proportional to the binding potential) was analyzed using linear regression and Pearson’s correlation (r). Age and regional β2-nAChR availability were inversely correlated in seven of the eight brain regions analyzed, with decline ranging from 32% (thalamus) to 18% (occipital cortex) over the adult lifespan, or up to 5% per decade. These results in living human subjects corroborate postmortem reports of decline in high affinity nicotine binding with age and may aid in elucidating the role of β2-nAChRs in cognitive aging.
doi:10.1016/j.neurobiolaging.2007.12.008
PMCID: PMC3523217  PMID: 18242781
nicotinic receptors; aging; [123I]5-IA-85380; SPECT
5.  Brain β2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler 
The Nicotrol® (Pfizer, USA) nicotine inhaler reduces craving by mimicking the behavioural component of cigarettes and delivering controlled doses of nicotine, which binds to the beta-2 subunit-containing nicotinic acetylcholine receptors (β2*-nAChRs). Previous studies examined β2*-nAChR occupancy after administration of regular and low-nicotine cigarettes. Here, we measured occupancy of β2*-nAChRs after administration of nicotine via inhaler, and the relationship between occupancy and changes in craving for tobacco smoking and withdrawal symptoms. Tobacco smokers participated in [123I]5-IA-85380 SPECT studies with either a nicotine inhaler (n=9) or tobacco cigarette (n=4) challenge. [123I]5-IA was administered as a bolus plus constant infusion. After equilibrium was achieved, three 30-min baseline scans were collected, and subjects either used the nicotine inhaler or a regular cigarette, and up to six additional scans were obtained. Receptor occupancy was determined based on the Lassen plot method. Craving for tobacco smoking and withdrawal symptoms were evaluated pre- and post-challenge. Use of the nicotine inhaler produced an average 55.9±6.4% occupancy of β2*-nAChRs 2–5 h post-challenge, whereas use of a cigarette produced significantly higher receptor occupancy (F=10.6, p=0.009) with an average 67.6±14.1% occupancy 1.5–5 h post-challenge. There was a significant decrease in withdrawal symptoms post-nicotine inhaler use (F=6.13, p=0.04). These results demonstrate significant differences in occupancy of β2*-nAChRs by nicotine after use of the inhaler vs. a cigarette and confirm the ability of the nicotine inhaler to relieve withdrawal symptoms.
doi:10.1017/S1461145710001227
PMCID: PMC3510008  PMID: 21029513
β2*-nAChR occupancy; nicotine; nicotine inhaler; SPECT brain imaging
6.  Anterior and Posterior Cingulate Cortex Volume in Healthy Adults: Effects of Aging and Gender Differences 
Brain research  2011;1401:18-29.
The cingulate cortex frequently shows gray matter loss with age as well as gender differences in structure and function, but little is known about whether individual cingulate Brodmann areas show gender-specific patterns of age-related volume decline. This study examined age-related changes, gender differences, and the interaction of age and gender in the relative volume of cingulate gray matter in areas 25, 24, 31, 23, and 29, over seven decades of adulthood. Participants included healthy, age-matched men and women, aged 20–87 (n = 70). Main findings were: (1) The whole cingulate showed significant age-related volume declines (averaging 5.54% decline between decades, 20s–80s). Each of the five cingulate areas also showed a significant decline with age, and individual areas showed different patterns of decline across the decades: Smaller volume with age was most evident in area 31, followed by 25 and 24. (2) Women had relatively larger cingulate gray matter volume than men overall and in area 24. (3) Men and women showed different patterns of age-related volume decline in area 31, at midlife and late in life. By delineating normal gender differences and age-related morphometric changes in the cingulate cortex over seven decades of adulthood, this study improves the baseline for comparison with structural irregularities in the cingulate cortex associated with psychopathology. The Brodmann area-based approach also facilitates comparisons across studies that aim to draw inferences between age- and gender-related structural differences in the cingulate gyrus and corresponding differences in cingulate function.
doi:10.1016/j.brainres.2011.05.050
PMCID: PMC3134959  PMID: 21669408
Cingulate cortex; aging; gender differences; MRI; gray matter; morphometry
7.  Dorso- and Ventro-lateral Prefrontal Volume and Spatial Working Memory in Schizotypal Personality Disorder 
Behavioural brain research  2010;218(2):335-340.
Schizotypal personality disorder (SPD) individuals and borderline personality disorder (BPD) individuals have been reported to show neuropsychological impairments and abnormalities in brain structure. However, relationships between neuropsychological function and brain structure in these groups are not well understood. This study compared visual-spatial working memory (SWM) and its associations with dorsolateral prefrontal cortex (DLPFC) and ventrolateral prefrontal cortex (VLPFC) gray matter volume in 18 unmedicated SPD patients with no BPD traits, 18 unmedicated BPD patients with no SPD traits, and 16 healthy controls (HC). Results showed impaired SWM in SPD but not BPD, compared with HC. Moreover, among the HC group, but not SPD patients, better SWM performance was associated with larger VLPFC (BA44/45) gray matter volume (Fisher's Z p-values<0.05). Findings suggest spatial working memory impairments may be a core neuropsychological deficit specific to SPD patients and highlight the role of VLPFC subcomponents in normal and dysfunctional memory performance.
doi:10.1016/j.bbr.2010.11.042
PMCID: PMC3049905  PMID: 21115066
working memory; borderline personality disorder; schizotypal personality disorder; dorsolateral prefrontal cortex; ventrolateral prefrontal cortex; MRI
8.  Effects of sex and normal aging on regional brain activation during verbal memory performance 
Neurobiology of aging  2008;31(5):826-838.
This study examined the main and interactive effects of age and sex on relative glucose metabolic rate (rGMR) within gray matter of 39 cortical Brodmann areas (BAs) and the cingulate gyrus using 18FDG-PET during a verbal memory task in 70 healthy normal adults, aged 20–87 years. Women showed significantly greater age-related rGMR decline in left cingulate gyrus than men (BAs 25, 24, 23, 31, 29). Both groups showed a decline in the anterior cingulate—a neuroanatomical structure that mediates effective cognitive-emotional interactions (BAs 32, 24, 25), while the other frontal regions did not show substantial decline. No sex differences in rGMR were identified within temporal, parietal and occipital lobes. Sex differences were observed for rGMR within subcomponents of the cingulate gyrus with men higher in BA25 and BA29, but lower in BA24 and BA 23 compared to women. For men, better memory performance was associated with greater rGMR in BA24, whereas in women better performance was associated with orbitofrontal-BA12. These results suggest that both age-related metabolic decline and sex differences within frontal regions are more marked in medial frontal and cingulate areas, consistent with some age-related patterns of affective and cognitive change.
doi:10.1016/j.neurobiolaging.2008.10.005
PMCID: PMC2871327  PMID: 19027195
Aging; healthy adults; sex differences; 18FDG PET; cingulate; prefrontal cortex

Results 1-8 (8)