florbetapir-f-18 and Cognition-Disorders

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been associated with a history of repetitive head impacts. The neuropathological diagnosis is based on a specific pattern of tau deposition with minimal amyloid-beta deposition that differs from other disorders, including Alzheimer's disease. The feasibility of detecting tau and amyloid deposition in the brains of living persons at risk for CTE has not been well studied.. We used flortaucipir positron-emission tomography (PET) and florbetapir PET to measure deposition of tau and amyloid-beta, respectively, in the brains of former National Football League (NFL) players with cognitive and neuropsychiatric symptoms and in asymptomatic men with no history of traumatic brain injury. Automated image-analysis algorithms were used to compare the regional tau standardized uptake value ratio (SUVR, the ratio of radioactivity in a cerebral region to that in the cerebellum as a reference) between the two groups and to explore the associations of SUVR with symptom severity and with years of football play in the former-player group.. A total of 26 former players and 31 controls were included in the analysis. The mean flortaucipir SUVR was higher among former players than among controls in three regions of the brain: bilateral superior frontal (1.09 vs. 0.98; adjusted mean difference, 0.13; 95% confidence interval [CI], 0.06 to 0.20; P<0.001), bilateral medial temporal (1.23 vs. 1.12; adjusted mean difference, 0.13; 95% CI, 0.05 to 0.21; P<0.001), and left parietal (1.12 vs. 1.01; adjusted mean difference, 0.12; 95% CI, 0.05 to 0.20; P = 0.002). In exploratory analyses, the correlation coefficients in these three regions between the SUVRs and years of play were 0.58 (95% CI, 0.25 to 0.79), 0.45 (95% CI, 0.07 to 0.71), and 0.50 (95% CI, 0.14 to 0.74), respectively. There was no association between tau deposition and scores on cognitive and neuropsychiatric tests. Only one former player had levels of amyloid-beta deposition similar to those in persons with Alzheimer's disease.. A group of living former NFL players with cognitive and neuropsychiatric symptoms had higher tau levels measured by PET than controls in brain regions that are affected by CTE and did not have elevated amyloid-beta levels. Further studies are needed to determine whether elevated CTE-associated tau can be detected in individual persons. (Funded by Avid Radiopharmaceuticals and others.).

Topics: Adult; Aged; Aniline Compounds; Brain; Brain Chemistry; Brain Concussion; Case-Control Studies; Chronic Traumatic Encephalopathy; Cognition Disorders; Ethylene Glycols; Football; Humans; Male; Mental Disorders; Middle Aged; Plaque, Amyloid; Positron-Emission Tomography; Radiopharmaceuticals; tau Proteins; Tauopathies

Cerebrospinal fluid (CSF) biomarker studies have shown variable accuracy for diagnosis of Alzheimer's disease (AD); therefore, internal validation is recommended.. To investigate the correlation between CSF biomarkers and cerebral 18-Florbetapir positron emission tomography (Amyloid-PET) and calculate their sensitivity and specificity to obtain the optimal clinical cut-off points to diagnose the etiology of cognitive impairment.. We performed Amyloid-PET scans and CSF biomarker levels analyses in 68 subjects (50 with mild cognitive impairment, 11 with AD dementia, and 7 with non-AD dementia). Visual examination of Amyloid-PET scans was performed. CSF analyses were performed using standard sandwich ELISA.. Amyloid-PET was positive in 36 subjects, negative in 26, and inconclusive in 6. Optimal clinical cut-off points for CSF markers were the following: amyloid-β 1-42 (Aβ42) = 629 pg/ml, total tau (t-tau) = 532 pg/ml, phosphorylated tau (p-tau) = 88 pg/ml, and t-tau/Aβ42 ratio = 0.58. T-tau/Aβ42 ratio showed the best sensitivity and specificity (92 and 84%, respectively). T-tau and p-tau CSF levels (r2 = 0.867) followed by the t-tau and t-tau/Aβ42 CSF ratio (r2 = 0.666) showed the strongest inter-marker correlation. Interestingly, subjects with inconclusive Amyloid-PET showed intermediate values for all CSF markers between negative and positive Amyloid-PET groups.. CSF t-tau/Aβ42 ratio appears to be the most accurate AD CSF marker. The presence of intermediate values for CSF markers among the subjects with inconclusive Amyloid-PET suggests the presence of other dementias associated with AD pathology or intermediate phenotypes.

Topics: Aged; Amyloid beta-Peptides; Analysis of Variance; Aniline Compounds; Apolipoproteins E; Biomarkers; Cognition Disorders; Dementia; Ethylene Glycols; Female; Humans; Male; Middle Aged; Peptide Fragments; Positron-Emission Tomography; tau Proteins

Amyloid deposition is common in dementia with Lewy bodies, but its pathophysiological significance is unclear.. The objective of this study was to investigate the relationship between amyloid deposition and clinical profile, gray matter volume, and brain perfusion in dementia with Lewy bodies.. Dementia with Lewy bodies (n = 37), Alzheimer's disease (n = 20), and controls (n = 20) underwent a thorough clinical assessment, 3T MRI, and early- and late-phase. There were no significant differences between amyloid-positive and amyloid-negative dementia with Lewy bodies cases in age (P = .78), overall cognitive impairment (P = .83), level of functional impairment (P = .80), or any other clinical or cognitive scale. There were also no significant differences in hippocampal or gray matter volumes. However, amyloid-positive dementia with Lewy bodies cases had lower medial temporal lobe perfusion (P = .03) than amyloid-negative cases, although a combination of medial temporal lobe perfusion, hippocampal volume, and cognitive measures was unable to accurately predict amyloid status in dementia with Lewy bodies.. Amyloid deposition was not associated with differences in clinical or neuropsychological profiles in dementia with Lewy bodies, but was associated with imaging evidence of medial temporal lobe dysfunction. The presence of amyloid in dementia with Lewy bodies cannot be identified on the basis of clinical and other imaging features and will require direct assessment via PET imaging or CSF. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid; Aniline Compounds; Brain; Cognition Disorders; England; Ethylene Glycols; Female; Humans; Imaging, Three-Dimensional; Lewy Body Disease; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Prospective Studies; Tomography Scanners, X-Ray Computed

Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative) by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2%) were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%). Increasing age and presence of an APOE ε4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-β amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.

Topics: Aged; Alzheimer Disease; Amyloid; Amyloid beta-Peptides; Aniline Compounds; Brain; Cognition; Cognition Disorders; Dementia; Ethylene Glycols; Female; Humans; Male; Middle Aged; Parkinson Disease; Plaque, Amyloid; Positron-Emission Tomography

A growing body of evidence suggests that cardiovascular disease risk factors including hypertension may be linked to sporadic Alzheimer's disease (AD). It is well known that hypertension is associated with cerebrovascular disease and vascular dementia on the basis of vascular remodeling. However, the mechanisms linking hypertension and AD remain unclear.. We studied 197 patients with AD (86 male; mean age ± SD: 75.8 ± 7.4 years) from the Alzheimer's Disease Neuroimaging Initiative database with (n = 97) and without (n = 100) hypertension. We explored associations between hypertension and clinical, plasma, cerebrospinal fluid and imaging markers of AD pathology in order to elucidate the underlying mechanisms that may link AD and hypertension.. We found that patients with AD with hypertension had worse cognitive function (Alzheimer's disease Assessment Scale-cognitive subscale, P = 0.038) and higher neuropsychiatric symptom burden (Neuropsychiatric Inventory Questionnaire, P = 0.016) compared with those without hypertension. Patients with AD with hypertension showed reduced glucose hypometabolism in the right (P < 0.001) and left (P = 0.007) hippocampus. No differences were found in magnetic resonance imaging volumetric measurements, [. Although hypertension is associated with worse cognitive function, behavioural symptoms and hippocampal glucose hypometabolism, it is not associated with evidence of increased amyloid or tau pathology. Effective management of hypertension may potentially have a therapeutic role in the alleviation of symptoms in AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Aniline Compounds; Cognition; Cognition Disorders; Cost of Illness; Ethylene Glycols; Female; Glucose; Hippocampus; Humans; Hypertension; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Neuropsychological Tests; Positron-Emission Tomography; Psychiatric Status Rating Scales; Radiopharmaceuticals

Combining PET amyloid-β (Aβ) and tau imaging may be critical for tracking disease progression in Alzheimer's disease (AD).. We sought to characterize the relationship between Aβ and tau ligands as well as with other measures of pathology.. We conducted a multi-center observational study in early AD (MMSE >20) participants aged 50 to 85 y. The schedule included cognitive assessments (ADAS-Cog) and CSF measurement of Aβ and tau at baseline and 6 months; PET-CT imaging with Aβ ([18F]AV45) and tau ([18F]AV1451) ligands at baseline.. 22 participants took part in the study with 20 completing its 6-month duration and 12 having both tau and amyloid PET. The PET biomarker analysis revealed a strong negative correlation between age and tau in multiple regions. Entorhinal cortex tau and age interacted significantly in terms of cognitive change over 6 months which may have been to older participants deteriorating faster despite lower levels of cortical tau. Cortical Aβ associated with entorhinal cortex tau while CSF tau/Aβ ratio correlated strongly with cortical tau but not Aβ.. The negative relationship between age and cortical tau whereby younger patients with mild AD had relatively greater tau burden is potentially important. It suggests that younger-age onset AD may be primarily driven by tau pathology while AD developing later may depend on a multitude of pathological mechanisms. These data also suggest that PET-tau performs better than PET-amyloid in predicting the best validated AD diagnostic marker- the CSF total tau/Aβ ratio.

Topics: Aged; Aging; Alzheimer Disease; Amyloid beta-Peptides; Analysis of Variance; Aniline Compounds; Carbolines; Cognition Disorders; Ethylene Glycols; Female; Humans; Male; Neuropsychological Tests; Positron-Emission Tomography; Psychiatric Status Rating Scales; tau Proteins

Tau pathology is a hallmark of Alzheimer's disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent (18)F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Aging; Alzheimer Disease; Aniline Compounds; Apolipoproteins E; Brain; Cognition Disorders; Ethylene Glycols; Female; Humans; Male; Positron-Emission Tomography; Psychiatric Status Rating Scales; tau Proteins; Thiazoles; Young Adult

To examine associations between aggregate genetic risk and Alzheimer disease (AD) markers in stages preceding the clinical symptoms of dementia using data from 2 large observational cohort studies.. We computed polygenic risk scores (PGRS) using summary statistics from the International Genomics of Alzheimer's Project genome-wide association study of AD. Associations between PGRS and AD markers (cognitive decline, clinical progression, hippocampus volume, and β-amyloid) were assessed within older participants with dementia. Associations between PGRS and hippocampus volume were additionally examined within healthy younger participants (age 18-35 years).. Within participants without dementia, elevated PGRS was associated with worse memory (p = 0.002) and smaller hippocampus (p = 0.002) at baseline, as well as greater longitudinal cognitive decline (memory: p = 0.0005, executive function: p = 0.01) and clinical progression (p < 0.00001). High PGRS was associated with AD-like levels of β-amyloid burden as measured with florbetapir PET (p = 0.03) but did not reach statistical significance for CSF β-amyloid (p = 0.11). Within the younger group, higher PGRS was associated with smaller hippocampus volume (p = 0.05). This pattern was evident when examining a PGRS that included many loci below the genome-wide association study (GWAS)-level significance threshold (16,123 single nucleotide polymorphisms), but not when PGRS was restricted to GWAS-level significant loci (18 single nucleotide polymorphisms).. Effects related to common genetic risk loci distributed throughout the genome are detectable among individuals without dementia. The influence of this genetic risk may begin in early life and make an individual more susceptible to cognitive impairment in late life. Future refinement of polygenic risk scores may help identify individuals at risk for AD dementia.

Topics: Adolescent; Adult; Aged; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Atrophy; Biomarkers; Cognition Disorders; Cohort Studies; Early Diagnosis; Ethylene Glycols; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Hippocampus; Humans; Male; Memory Disorders; Multifactorial Inheritance; Polymorphism, Single Nucleotide; Positron-Emission Tomography; Young Adult

Reduced cerebrospinal fluid amyloid-β42 and increased retention of florbetapir positron emission tomography are biomarkers reflecting cortical amyloid load in Alzheimer's disease. However, these measurements do not always agree and may represent partly different aspects of the underlying Alzheimer's disease pathology. The goal of this study was therefore to test if cerebrospinal fluid and positron emission tomography amyloid-β biomarkers are independently related to other Alzheimer's disease markers, and to examine individuals who are discordantly classified by these two biomarker modalities. Cerebrospinal fluid and positron emission tomography amyloid-β were measured at baseline in 769 persons [161 healthy controls, 68 subjective memory complaints, 419 mild cognitive impairment and 121 Alzheimer's disease dementia, mean age 72 years (standard deviation 7 years), 47% females] and used to predict diagnosis, APOE ε4 carriage status, cerebral blood flow, cerebrospinal fluid total-tau and phosphorylated-tau levels (cross-sectionally); and hippocampal volume, fluorodeoxyglucose positron emission tomography results and Alzheimer's Disease Assessment Scale-cognitive subscale scores (longitudinally). Cerebrospinal fluid and positron emission tomography amyloid-β were highly correlated, but adjusting one of these predictors for the other revealed that they both provided partially independent information when predicting diagnosis, APOE ε4, hippocampal volume, metabolism, cognition, total-tau and phosphorylated-tau (the 95% confidence intervals of the adjusted effects did not include zero). Cerebrospinal fluid amyloid-β was more strongly related to APOE ε4 whereas positron emission tomography amyloid-β was more strongly related to tau levels (P < 0.05). Discordance (mainly isolated cerebrospinal fluid amyloid-β positivity) differed by diagnostic group (P < 0.001) and was seen in 21% of cognitively healthy people but only 6% in dementia patients. The finding that cerebrospinal fluid and positron emission tomography amyloid-β provide partially independent information about a wide range of Alzheimer's measures supports the theory that these modalities represent partly different aspects of Alzheimer's pathology. The fact that mismatch, with positive cerebrospinal fluid amyloid-β but normal positron emission tomography amyloid-β, is relatively common in cognitively healthy people may be considered when using these biomarkers to identify early stage Alzheimer's disease. R

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Apolipoprotein E4; Cognition Disorders; Cohort Studies; Ethylene Glycols; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Peptide Fragments; Positron-Emission Tomography

In this article, we describe an image analysis strategy with improved power for tracking longitudinal amyloid-β (Aβ) PET changes and evaluating Aβ-modifying treatments.. Our aims were to compare the power of template-based cerebellar, pontine, and cerebral white matter reference regions to track 24-mo florbetapir standardized uptake value (SUV) ratio (SUVR) changes; to relate those changes to 24-mo clinical declines; and to evaluate Aβ-modifying treatments in Aβ-positive (Aβ+) and Aβ-negative (Aβ-) patients with probable Alzheimer dementia (pAD), in patients with mild cognitive impairment (MCI), in cognitively normal controls (NCs), and in cognitively normal apolipoprotein E4 (APOE4) carriers and noncarriers. We used baseline and follow-up (∼24 mo) florbetapir PET scans from 332 Aβ+ and Aβ- subjects participating in the multicenter Alzheimer's Disease Neuroimaging Initiative. Each of the proposed analyses included 31 pAD patients, 187 MCI patients, and 114 NCs. Cerebral-to-white matter, cerebellar, and pontine SUVRs were characterized in terms of their longitudinal variability; their power to track longitudinal fibrillar Aβ increases in Aβ+ and Aβ- subgroups and cognitively normal APOE4 carriers and noncarriers; the sample sizes needed to detect attenuated accumulation of or clearance of fibrillar Aβ accumulation in randomized clinical trials; and their ability to relate 24-mo fibrillar Aβ increases to clinical declines.. As predicted, cerebral-to-white matter SUVR changes were significantly less variable and had significantly greater power to detect 24-mo fibrillar Aβ increases and evaluate Aβ-modifying treatment effects in Aβ+ pAD, MCI, and NC subjects and cognitively normal APOE4 carriers. They were also distinguished by the ability to detect significant associations between 24-mo Aβ increases and clinical declines.. A cerebral white matter reference region may improve the power to track longitudinal fibrillar Aβ increases, to characterize their relationship to longitudinal clinical declines, and to evaluate Aβ-modifying treatments in randomized clinical trials.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Apolipoprotein E4; Brain; Brain Mapping; Cerebellum; Cerebrum; Cognition Disorders; Ethylene Glycols; Female; Humans; Image Processing, Computer-Assisted; Longitudinal Studies; Male; Middle Aged; Pons; Positron-Emission Tomography; Randomized Controlled Trials as Topic; Reference Values; Sample Size; Time Factors; White Matter

Florbetapir (18F) for brain amyloid positron emission tomography (PET) imaging has been recently approved in Europe to estimate β-amyloid neuritic plaque density in the brain when the subject is still alive. Such density is one of the key issues for the definitive diagnosis of Alzheimer's disease (AD) at autopsy. This capability of florbetapir (18F) is regarded as a significant improvement in the diagnostic procedures for adult patients with cognitive impairment who are being evaluated for AD and other causes of cognitive impairment. The current paper highlights the specific characteristics of the European marketing authorization of florbetapir (18F).

Topics: Alzheimer Disease; Aniline Compounds; Brain; Cognition Disorders; Drug Approval; Ethylene Glycols; Europe; Fluorine Radioisotopes; Humans; Plaque, Amyloid; Positron-Emission Tomography; Radiopharmaceuticals; Risk; Sensitivity and Specificity

Abnormal β-amyloid (Aβ) is associated with deleterious changes in central acetylcholinergic tone in the very early stages of Alzheimer's disease (AD), which may be unmasked by a cholinergic antagonist. We aimed to establish an optimal "microdose" of scopolamine for the development of a "cognitive stress test.". Healthy older adults (n = 26, aged 55-75 years) with two risk factors for AD, but with low cortical Aβ burden, completed the Groton Maze Learning Test (GMLT) at baseline and then received scopolamine (0.20 mg subcutaneously). Participants were reassessed at 1, 3, 5, 7, and 8 hours postinjection.. There were significant differences, of a moderate magnitude, in performance between baseline and 3 hours postinjection for total errors, rule break errors, and the GMLT composite (d ≈ 0.50) that were all unrelated to body mass.. A very low dose of scopolamine leads to reliable cognitive impairment at 3 hours postdose (Tmax) and full cognitive recovery within 5 hours, supporting its use as a prognostic test paradigm to identify individuals with potential preclinical AD. This paradigm is being implemented in a larger cohort of healthy adults, with high or low Aβ, to identify pharmacodynamic differences between groups.

Topics: Aged; Alzheimer Disease; Analysis of Variance; Aniline Compounds; Cholinergic Antagonists; Cognition Disorders; Cohort Studies; Dose-Response Relationship, Drug; Early Diagnosis; Ethylene Glycols; Female; Humans; Male; Maze Learning; Middle Aged; Mood Disorders; Neuropsychological Tests; Positron-Emission Tomography; Psychiatric Status Rating Scales; Scopolamine; Time Factors; Tomography Scanners, X-Ray Computed

Prevalence and risk factors for focal hemosiderin deposits are important considerations when planning amyloid-modifying trials for treatment and prevention of Alzheimer's disease (AD).. Subjects were cognitively normal (n = 171), early-mild cognitive impairment (MCI) (n = 240), late-MCI (n = 111), and AD (n = 40) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Microhemorrhages and superficial siderosis were assessed at baseline and on all available MRIs at 3, 6, and 12 months. β-amyloid load was assessed with (18)F-florbetapir positron emission tomography.. Prevalence of superficial siderosis was 1% and prevalence of microhemorrhages was 25% increasing with age (P < .001) and β-amyloid load (P < .001). Topographic densities of microhemorrhages were highest in the occipital lobes and lowest in the deep/infratentorial regions. A greater number of microhemorrhages at baseline was associated with a greater annualized rate of additional microhemorrhages by last follow-up (rank correlation = 0.49; P < .001).. Focal hemosiderin deposits are relatively common in the ADNI cohort and are associated with β-amyloid load.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Analysis of Variance; Aniline Compounds; Apolipoprotein E4; Cognition Disorders; Cohort Studies; Disease Progression; Ethylene Glycols; Female; Hemosiderosis; Humans; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Positron-Emission Tomography; Time Factors

To examine the association between regional brain uptake of a novel amyloid positron emission tomography (PET) tracer florbetapir F 18 ([(18)F]-AV-45) and cognitive performance in a pilot study.. Cross-sectional comparison of [(18)F]-AV-45 in AD patients versus controls.. Three specialty memory clinics.. Eleven participants with probable Alzheimer disease (AD) by NINDS/ADRDA criteria and 15 healthy comparison (HC) participants.. Participants underwent PET imaging following a 370 MBq (10 mCi) intravenous administration of [(18)F]-AV-45. Regional/cerebellar standardized uptake value ratios (SUVRs) were calculated. Cognition was assessed using Mini-Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), Wechsler Logical Memory IA (immediate recall) test (LMIA), and verbal category fluency.. Greater [(18)F]-AV-45 SUVR was associated with poorer performance on all cognitive tests. In the HC group, occipital, parietal, precuneus, temporal, and cortical average SUVR was associated with greater ADAS-Cog, and greater anterior cingulate SUVR was associated with lower LMIA. Two HC participants had [(18)F]-AV-45 cortical/cerebellar SUVR greater than 1.5, one of whom had deficits in episodic recall and on follow-up met criteria for amnestic mild cognitive impairment.. [(18)F]-AV-45 SUVR in several brain regions was associated with worse global cognitive performance particularly in HC, suggesting its potential as a marker of preclinical AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid; Aniline Compounds; Biomarkers; Brain; Case-Control Studies; Cognition; Cognition Disorders; Ethylene Glycols; Female; Fluorine Radioisotopes; Humans; Male; Middle Aged; Neuropsychological Tests; Pilot Projects; Positron-Emission Tomography

Topics: Alzheimer Disease; Aniline Compounds; Cognition Disorders; Ethylene Glycols; Humans; Positron-Emission Tomography; Predictive Value of Tests

Topics: Adult; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Cognition Disorders; Drug Approval; Ethylene Glycols; Humans; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity; United States; United States Food and Drug Administration

Florbetapir F 18 PET can image amyloid-β (Aβ) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting Aβ pathology using florbetapir PET in subjects at risk for progressive cognitive decline.. A total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (Aβ+) or negative (Aβ-) for pathologic levels of β-amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined from the baseline PET images. Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status. Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline.. In both MCI and CN, baseline Aβ+ scans were associated with greater clinical worsening on the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog (p < 0.01) and Clinical Dementia Rating-sum of boxes (CDR-SB) (p < 0.02). In MCI Aβ+ scans were also associated with greater decline in memory, Digit Symbol Substitution (DSS), and Mini-Mental State Examination (MMSE) (p < 0.05). In MCI, higher baseline SUVr similarly correlated with greater subsequent decline on the ADAS-Cog (p < 0.01), CDR-SB (p < 0.03), a memory measure, DSS, and MMSE (p < 0.05). Aβ+ MCI tended to convert to AD dementia at a higher rate than Aβ- subjects (p < 0.10).. Florbetapir PET may help identify individuals at increased risk for progressive cognitive decline.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Brain; Cognition Disorders; Cognitive Dysfunction; Dementia; Ethylene Glycols; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Neuropsychological Tests; Positron-Emission Tomography; Predictive Value of Tests; Psychiatric Status Rating Scales; Psychomotor Performance; Radiopharmaceuticals; Risk

Topics: Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Brain; Cognition Disorders; Diagnosis, Differential; Drug Approval; Ethylene Glycols; Fluorine Radioisotopes; Injections; Plaque, Amyloid; Positron-Emission Tomography; United States; United States Food and Drug Administration

Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) population, we examined (1) cross-sectional relationships between amyloid deposition, hypometabolism, and cognition, and (2) associations between amyloid and hypometabolism measurements and longitudinal cognitive measurements.. We examined associations between mean cortical florbetapir uptake, mean (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) within a set of predefined regions, and Alzhiemer's Disease Assessment Scale (ADAS-cog) performance in 426 ADNI participants (126 normal, 162 early mild cognitive impairment [EMCI], 85 late MCI [LMCI], 53 Alzheimer disease [AD] patients). For a subset of these (76 normal, 81 LMCI) we determined whether florbetapir and FDG-PET were associated with retrospective decline in longitudinal ADAS-cog measurements.. Twenty-nine percent of normal subjects, 43% of EMCI patients, 62% of LMCI patients, and 77% of AD patients were categorized as florbetapir positive. Florbetapir was negatively associated with concurrent FDG and ADAS-cog in both MCI groups. In longitudinal analyses, florbetapir-positive subjects in both normal and LMCI groups had greater ongoing ADAS-cog decline than those who were florbetapir negative. However, in normal subjects, florbetapir positivity was associated with greater ADAS-cog decline than FDG, whereas in LMCI, FDG positivity was associated with greater decline than florbetapir.. Although both hypometabolism and β-amyloid (Aβ) deposition are detectable in normal subjects and all diagnostic groups, Aβ showed greater associations with cognitive decline in normal participants. In view of the minimal cognitive deterioration overall in this group, this suggests that amyloid deposition has an early and subclinical impact on cognition that precedes metabolic changes. At moderate and later stages of disease (LMCI/AD), hypometabolism becomes more pronounced and more closely linked to ongoing cognitive decline.

Topics: Aged; Amyloid; Aniline Compounds; Body Burden; Cognition Disorders; Cognitive Dysfunction; Cross-Sectional Studies; Disease Progression; Ethylene Glycols; Female; Fluorodeoxyglucose F18; Humans; Image Processing, Computer-Assisted; Longitudinal Studies; Male; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography