18F-Florbetaben PET beta-amyloid binding expressed in Centiloids

Tc-99m HMPAO brain SPECT findings in mild and moderate Alzheimer's disease: Correlation with event related potentials

Imaging of amyloid β in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism

Alpha rhythms in mild dements during visual delayed choice reaction time tasks: A MEG study

Movement-related cortical potentials (MRCP) were measured in young normal subjects (age < 40) and aged normal subjects (age > or = 60). All were right-handed. MRCPs were recorded for voluntary self-paced extension of the right middle finger or the right foot. For the middle finger extension the latency and slope of the Bereitschaftspotential (BP) and the negative slope (NS') were measured at the contralateral hand motor area, and for the foot movement they were measured from Cz. MRCPs for the finger extension were examined in 12 young subjects (5 men, 7 women, 22-38 years old, mean age 26.3 +/- 5.2 years) and 18 aged subjects (9 men, 9 women, 60-82 years old, mean age 69.4 +/- 7.2 years). BP latency and NS' latency were significantly longer in the aged subjects than in the young subjects (p < 0.001 and p < 0.05, respectively). MRCPs for the foot movement were measured in 10 young subjects (3 men, 7 women, 22-38 years old, mean age 27.1 +/- 5.4 years) and 10 aged subjects (5 men, 5 women, 60-82 years old, mean age 70.3 +/- 8.1 years). BP latency was significantly longer in the aged subjects than in the young subjects (p < 0.05), but NS' latency was not. For both finger and foot extension, neither BP slope nor NS' slope differed significantly between the groups, although both slopes were steeper in the young subjects than the aged ones. These findings suggest that the time required by the cerebrum to prepare for voluntary movement and the period of preparation for movement are longer in aged subjects than in young subjects.

To investigate the association between brain amyloid load in Alzheimer disease (AD) measured by [11C]PIB-PET, regional cerebral glucose metabolism (rCMRGlc) measured by [18F]FDG-PET, and cognition. Nineteen subjects with AD and 14 controls had [11C]PIB-PET and underwent a battery of psychometric tests. Twelve of those subjects with AD and eight controls had [18F]FDG-PET. Parametric images of [11C]PIB binding and rCMRGlc were interrogated with a region-of-interest atlas and statistical parametric mapping. [11C]PIB binding and rCMRGlc were correlated with scores on psychometric tests. AD subjects showed twofold increases in mean [11C]PIB binding in cingulate, frontal, temporal, parietal, and occipital cortical areas. Higher cortical amyloid load correlated with lower scores on facial and word recognition tests. Two patients fulfilling the clinical criteria for AD had normal [11C]PIB at baseline. Over 20 months this remained normal in one but increased in the cingulate of the other. Mean levels of temporal and parietal rCMRGlc were reduced by 20% in AD and these correlated with mini mental scores, immediate recall, and recognition memory test for words. Higher [11C]PIB uptake correlated with lower rCMRGlc in temporal and parietal cortices. [11C]PIB-PET detected an increased amyloid plaque load in 89% of patients with clinically probable Alzheimer disease (AD). The high frontal amyloid load detected by [11C]PIB-PET in AD in the face of spared glucose metabolism is of interest and suggests that amyloid plaque formation may not be directly responsible for neuronal dysfunction in this disorder.

To investigate the safety, acceptability, and feasibility of positron emission tomography (PET) using carbon 11-labeled Pittsburgh Compound B ([(11)C]PiB) to measure cerebral β-amyloid in adults with Down syndrome (DS) and to explore if the technique differentiates between participants with and without Alzheimer disease (AD). Proof-of-principle case-controlled study of a nonrandomly selected cohort of participants with DS (with or without AD) compared within group and with healthy controls without DS. All had dynamic [(11)C]PiB PET and magnetic resonance imaging. Carbon 11-labeled PiB binding in the regions of interest associated with AD was quantitatively analyzed. Wolfson Brain Imaging Centre, Cambridge, England. Nine with DS (aged 25-64 years), of whom 5 had a diagnosis of AD, and 14 healthy controls without DS (aged 33-69 years). Positive [(11)C]PiB binding in regions of interest. The scanning process was feasible and acceptable with no adverse events or safety concerns. Maps and regional values of nondisplaceable binding potential were produced using the reference tissue-input Logan plot, with the cerebellum used as the reference tissue. When compared with the healthy control group without DS, only participants with DS older than 45 years had significant [(11)C]PiB binding in regions of interest usually associated with AD, whether or not they had clinical evidence of dementia. Dynamic [(11)C]PiB PET can be used successfully to measure cerebral β-amyloid deposition in DS. A clinical diagnosis of AD and age appear to be predictors of [(11)C]PiB binding in regions of interest, but given the small numbers, we cannot generalize the results.

IntroductionSolanezumab is a monoclonal antibody that preferentially binds soluble amyloid beta and promotes its clearance from the brain. The aim of this post hoc analysis was to assess the effect of low‐dose solanezumab (400 mg) on global brain volume measures in patients with mild or moderate Alzheimer's disease (AD) dementia quantified using volumetric magnetic resonance imaging (vMRI) data from the EXPEDITION clinical trial program.MethodsPatients with mild or moderate AD (EXPEDITION and EXPEDITION2) and mild AD (EXPEDITION3), were treated with either placebo or solanezumab (400 mg) every 4 weeks (Q4W) for 76 weeks. vMRI scans were acquired at baseline and at 80 weeks from 427 MRI facilities using a standardized imaging protocol. Whole brain volume (WBV) and ventricle volume (VV) changes were estimated at 80 weeks using either boundary shift integral (EXPEDITION and EXPEDITION2) or tensor‐based morphometry (EXPEDITION3).ResultsThe pooled cohort used for this study consisted of participants with vMRI at baseline and week 80 across the three trials. Analyzed patient subgroups comprised full patient cohort (N = 2933), apolipoprotein E (APOE) ε4+ carriers (N = 1835), and patients with mild (N = 2497) or moderate AD dementia (N = 428). No significant effect (all P‐values ≥.05) of treatment was observed in the pooled sample, individual trials, or subgroups of patients with mild or moderate AD or APOE ε4 carriers, in either WBV or VV change.DiscussionAnalysis of patients with mild or moderate AD dementia from baseline to 80 weeks using vMRI measures of WBV and VV changes suggested that low‐dose solanezumab was not linked to changes in volumes at 80 weeks. Analysis of the pooled cohort did not demonstrate an effect on brain volumes with treatment. Evaluation of a higher dose of solanezumab in the preclinical stage of AD is currently being undertaken.

AimMATRICS Consensus Cognitive Battery was developed by the National Institute of Mental Health to establish acceptance criteria for measuring cognitive changes in schizophrenia and can be used to assess cognitive functions in other psychiatric disorders. We used a Japanese version of MATRICS Consensus Cognitive Battery to explore the changes in multiple cognitive functions in patients with mild cognitive impairment and mild Alzheimer's disease.MethodsWe administered the Japanese version of MATRICS Consensus Cognitive Battery to 11 patients with mild cognitive impairment (MCI), 11 patients with Alzheimer's disease, and 27 healthy controls. All Japanese versions of MATRICS Consensus Cognitive Battery domain scores were converted to t‐scores using sample means and standard deviations and were compared for significant performance differences among healthy control, MCI, and mild Alzheimer's disease groups.ResultsCompared with healthy controls, patients with MCI and mild Alzheimer's disease demonstrated the same degree of impairment to processing speed, verbal learning, and visual learning. Reasoning and problem‐solving showed significant impairments only in mild Alzheimer's disease. Verbal and visual abilities in working memory showed different performances in the MCI and mild Alzheimer's disease groups, with the Alzheimer's disease group demonstrating significantly more deficits in these domains. No significant difference was found among the groups in attention/vigilance and social cognition.ConclusionsThe Japanese version of MATRICS Consensus Cognitive Battery can be used to elucidate the characteristics of cognitive dysfunction of normal aging, MCI, and mild dementia in clinical practice.

Alzheimer’s disease (AD) can manifest itself with prominent language dysfunction. Incompleteness in discourse refers to the lack of indispensable sentence-constructing elements that hinder communication fluency and accuracy. The current study investigates how the pattern of incompleteness is associated with the descriptive discourse produced by elders without AD and those with different stages of AD. The Chinese discourse samples were collected from the picture description of 40 elders with mild probable AD (Mini-Mental State Examination (MMSE) 21–26, Montreal Cognitive Assessment Scale-Basic (MoCA-B) 15–19), 40 elders with moderate probable AD (MMSE 11–20, MoCA-B 10–14), and 40 controls (MMSE 26–29, MoCA-B 24–29). The total production of incomplete sentences and six incompleteness features were examined. The Mild AD, Moderate AD, and Control groups differed in the total output of the incomplete sentence. Group differences also emerged in four incompleteness features: missing subject, missing predicate, missing object, and missing functional word. The Moderate AD group differed from the Mild AD group with respect to most significant features, while Mild AD and Control groups were very similar. The results suggested that AD impairs the sentence construction ability of Chinese elders, especially at the later stage. These statistically significant differences between the groups might provide some references when diagnosing the risk and possibility of cognitive impairment of Chinese elders, facilitating the design of clinical evaluation or screening for probable AD.

IC-P-068: Diffusion tensor imaging of normal appearing white matter in MCI and AD

Patients affected by sporadic Alzheimer disease (AD) show a significant alteration of amyloid precursor protein (APP) forms in platelets when compared with patients with dementia but without AD and age-matched controls. To evaluate the ratio of platelet APP forms (APPr) in early-stage AD and mild cognitive impairment (MCI) and its potential as a biomarker for the early identification of AD. Community population-based sample of patients admitted to 4 AD centers for investigation of cognitive disturbances. Thirty-five patients with mild AD (mAD), 21 patients with very mild AD (vmAD), 30 subjects with MCI, and 25 age-matched controls were included. The APPr was evaluated by Western blot analysis in platelet homogenate. Compared with controls (mean +/- SD, 0.93 +/- 0.3), the mean APPr was decreased in patients with mAD (0.44 +/- 0.24; P<.001) and patients with vmAD (0.49 +/- 0.3; P<.001). Regarding the MCI group, a significant decrease in APPr was found compared with controls (0.62 +/- 0.33; P<.001). Fixing a cutoff score of 0.6, sensitivity was 88.6% (31/35) for patients with mAD and 85.7% (18/21) for patients with vmAD, whereas specificity was 88% (22/25) for controls. Among patients with MCI, 18 (60%) of 30 individuals displayed APPr values below the cutoff. Alteration of platelet APP forms is an early event in AD, and the measurement of APPr may be useful for the identification of preclinical AD in patients with MCI.

Donepezil provides greater benefits in mild compared to moderate Alzheimer's disease: Implications for early diagnosis and treatment

Validation of a novel cognitive composite assessment for mild and prodromal Alzheimer's disease

Aging is associated with changes of the systolic blood pressure that may increase cardiac work and myocardial blood flow at rest and reduce the myocardial flow reserve. This might be misinterpreted as age-related impairment of the coronary vasodilator capacity. Myocardial blood flow was quantified at rest and after administration of intravenous dipyridamole in 40 healthy volunteers (12 women and 28 men) with 13N-ammonia and positron emission tomography. Eighteen of the normal subjects were less than and 22 were older than 50 years (31 +/- 9 versus 64 +/- 9 years). The resting rate-pressure product was lower in the younger than in the older subjects (6895 +/- 1070 versus 8634 +/- 1890; P < 0.01). Myocardial blood flow at rest averaged 0.76 +/- 0.17 mL.min-1.g-1 in the younger volunteers and 0.92 +/- 0.25 mL.min-1.g-1 in the older volunteers (P < 0.05). Hyperemic blood flows did not differ between younger and older subjects (3.0 +/- 0.8 versus 2.7 +/- 0.6 mL.min-1.g-1; P = NS); however, minimal coronary resistance was higher in the older subjects. Corrected for indexes of coronary driving pressure, hyperemic flow was lower in older than in younger normal subjects. The higher resting blood flows combined with similar hyperemic flows resulted in a lower myocardial flow reserve in the older than in the younger normal subjects (4.1 +/- 0.9 versus 3.0 +/- 0.70; P < 0.0001). The flow reserve was more closely correlated with resting than with hyperemic blood flows. Aging does not alter significantly dipyridamole-induced hyperemic flows; although coronary vascular resistance after dipyridamole was somewhat increased in older subjects. The gradual decline of the myocardial blood flow reserve correlates with an age-related increase of baseline myocardial work and blood flow. These findings suggest that the reduced flow reserve with age is primarily due to increased cardiac work and blood flow at rest rather than to an abnormal vasodilator capacity.

Susceptibility-weighted imaging (SWI) microscopy on a 7.0T system demonstrated the corticomedullary junction (CMJ) to be a high-susceptibility region (HSR) in young normal subjects, suggesting that functional alteration of cortical microcirculation could be assessed with this imaging method. Focused microscopic studies were performed on the parietal association cortex in 74 normal volunteers (ages 20-79 years; 35 female, 39 male) using a SWI algorithm on a system constructed based on General Electric Signa LX (Waukesha, WI, USA), equipped with a 900-mm clear bore superconducting magnet operating at 7.0T. There was a clear-cut reduction in the thickness of the normal-appearing cortex (cortex, R2 = .5290, P < .001) and expansion of CMJ-HSR (R(2) = .6919, P < .001). The sum of cortex thickness and CMJ-HSR thickness was essentially constant, suggesting that the observed expansion of CMR-HSR with aging likely occurred within the cortical mantle. CMJ-HSR expands significantly as a function of aging. Since CMJ-HSR represents a functionally distinct area with relatively slow venous flow, the observed expansion is believed to reflect alteration in cerebral microcirculation with increased age, providing another clue for pathogenesis of Alzheimer's disease.