Positron emission tomography (PET) may increase the diagnostic accuracy and confirm the underlying neuropathologic changes of Alzheimer disease (AD). OBJECTIVE To determine the accuracy of antemortem [ 18 F]flortaucipir PET images for predicting the presence of AD-type tau pathology at autopsy. DESIGN, SETTING, AND PARTICIPANTS This diagnostic study (A16 primary cohort) was conducted from October 2015 to June 2018 at 28 study sites (27 in US sites and 1 in Australia). Individuals with a terminal illness who were older than 50 years and had a projected life expectancy of less than 6 months were enrolled. All participants underwent [ 18 F]flortaucipir PET imaging, and scans were interpreted by 5 independent nuclear medicine physicians or radiologists. Supplemental autopsy [ 18 F]flortaucipir images and pathological samples were also collected from 16 historically collected cases. A second study (FR01 validation study) was conducted from March 26 to April 26, 2019, in which 5 new readers assessed the original PET images for comparison to autopsy. MAIN OUTCOMES AND MEASURES [ 18 F]flortaucipir PET images were visually assessed and compared with immunohistochemical tau pathology. An AD tau pattern of flortaucipir retention was assessed for correspondence with a postmortem B3-level (Braak stage V or VI) pathological pattern of tau accumulation and to the presence of amyloid-β plaques sufficient to meet the criteria for high levels of AD neuropathological change. Success was defined as having at least 3 of the 5 readers above the lower bounds of the 95% CI for both sensitivity and specificity of 50% or greater. RESULTS A total of 156 patients were enrolled in the A16 study and underwent [ 18 F]flortaucipir PET imaging. Of these, 73 died during the study, and valid autopsies were performed for 67 of these patients. Three autopsies were evaluated as test cases and removed from the primary cohort (n = 64). Of the 64 primary cohort patients, 34 (53%) were women and 62 (97%) were white; mean (SD) age was 82.5 (9.6) years; and 49 (77%) had dementia, 1 (2%) had mild cognitive impairment, and 14 (22%) had normal cognition. Prespecified success criteria were met for the A16 primary cohort. The flortaucipir PET scans predicted a B3 level of tau pathology, with sensitivity ranging from 92.3% (95% CI, 79.7%-97.3%) to 100.0% (95% CI, 91.0%-100.0%) and specificity ranging from 52.0% (95% CI, 33.5%-70.0%) to 92.0% (95% CI, 75.0%-97.8%). A high level of AD neuropathological change was predicted with sensitivity of 94.7% (95% CI, 82.7%-98.5%) to 100.0% (95% CI, 90.8%-100.0%) and specificity of 50.0% (95% CI, 32.1%-67.9%) to 92.3% (95% CI, 75.9%-97.9%). The FR01 validation study also met prespecified success criteria. Addition of the supplemental autopsy data set and 3 test cases, which comprised a total of 82 patients and autopsies for both the A16 and FR01 studies, resulted in improved specificity and comparable overall accuracy. Among the 156 enrolled participants, 14 (9%) experienced at least 1 treatment-emergent adverse event. CONCL...

Resting anterior cingulate and dorsolateral prefrontal cortex rCBF is significantly related to decision making, as assessed by the Gambling Task.

Background: The current evidence is inconclusive to support the benefits of aerobic exercise training (AET) for preventing neurocognitive decline in patients with amnestic mild cognitive impairment (aMCI). Objective: To examine the effect of a progressive, moderate-to-high intensity AET program on memory and executive function, brain volume, and cortical amyloid-␤ (A␤) plaque deposition in aMCI patients. Methods: This is a proof-of-concept trial that randomized 70 aMCI patients to 12 months of AET or stretching and toning (SAT, active control) interventions. Primary neuropsychological outcomes were assessed by using the California Verbal Learning Test-second edition (CVLT-II) and the Delis-Kaplan Executive Function System (D-KEFS). Secondary outcomes were the global and hippocampal brain volumes and the mean cortical and precuneus A␤ deposition.

Comparison is made with several other SPECT and PET series with histopathologic correlation. Brain blood flow SPECT is useful in the diagnosis and differential diagnosis of the dementias.

Changes in the brain's cholinergic receptor systems underlie several neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, and depression. An emerging preclinical literature also reveals that acetylcoholine may have an important function in addictive processes, including reward, learning, and memory. This study was designed to assess alterations in cholinergic receptor systems in limbic regions of abstinent cocaine-addicted subjects compared with healthy controls. On three separate days, 23 1-to 6-week abstinent, cocaine-(and mostly nicotine-) addicted subjects and 22 sex-, age-, and race-matched control subjects were administered the muscarinic and nicotinic cholinergic agonist physostigmine, the muscarinic antagonist scopolamine, and saline. Regional cerebral blood flow (rCBF) after each infusion was determined using single photon emission-computed tomography. Both cholinergic probes induced rCBF changes (po0.005) in relatively distinct, cholinergic-rich, limbic brain regions. After physostigmine, cocaine-addicted subjects showed altered rCBF, relative to controls, in limbic regions, including the left hippocampus, left amygdala, and right insula. Group differences in the right dorsolateral prefrontal cortex, posterior cingulate, and middle temporal gyrus were also evident. Scopolamine also revealed group differences in the left hippocampus and right insula as well as the posterior cingulate and middle temporal gyrus. Cocaine addicted and controls differ in their subcortical, limbic, and cortical response to cholinergic probes in areas relevant to craving, learning, and memory. Cholinergic systems may offer a pharmacologic target for cocaine addiction treatment.