Alzheimer's Disease Normal Control Research Articles

Zoom-In Neural Network Deep-Learning Model for Alzheimer's Disease Assessments.

Deep neural networks have been successfully applied to generate predictive patterns from medical and diagnostic data. This paper presents an approach for assessing persons with Alzheimer's disease (AD) mild cognitive impairment (MCI), compared with normal control (NC) persons, using the zoom-in neural network (ZNN) deep-learning algorithm. ZNN stacks a set of zoom-in learning units (ZLUs) in a feedforward hierarchy without backpropagation. The resting-state fMRI (rs-fMRI) dataset for AD assessments was obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The Automated Anatomical Labeling (AAL-90) atlas, which provides 90 neuroanatomical functional regions, was used to assess and detect the implicated regions in the course of AD. The features of the ZNN are extracted from the 140-time series rs-fMRI voxel values in a region of the brain. ZNN yields the three classification accuracies of AD versus MCI and NC, NC versus AD and MCI, and MCI versus AD and NC of 97.7%, 84.8%, and 72.7%, respectively, with the seven discriminative regions of interest (ROIs) in the AAL-90.

Neuropsychological correlates of the P300 in patients with Alzheimer's disease

The P300 is a useful psychophysiological index that reflects cognitive functions; however, the relationship between P300 indices and neuropsychological tests in Alzheimer's disease (AD) patients is unclear. Thirty-one AD patients and 31 elderly normal control (NC) subjects were recruited. Age and education level were matched between the two groups. The relationship between the P300 and the Korean version of the Consortium to Establish a Registry for Alzheimer's disease (CERAD-K) assessment packet (including 11 neuropsychological tests) was examined in AD patients. Compared to the NC subjects, the AD patients exhibited significantly decreased P300 amplitudes; however, there was no significant difference between the two groups in terms of P300 latency. After a permutation-based correction for multiple tests, P300 amplitudes at the Cz and Pz electrodes were significantly correlated with performance on the word list recognition, constructional praxis, and word fluency neuropsychological tests in the AD patients. Additionally, P300 latencies at the Pz and C6 electrodes were also significantly correlated with performance on the Mini-Mental State Examination, CERAD-K version (MMSE-K), and Trail Making Test part A (TMT-A) neuropsychological tests in the AD patients. The results suggest that the P300 is responsive to the deterioration of language, memory, and executive functions observed in AD patients. Although there was no significant difference between the AD patients and NC subjects in the P300 latency, P300 latency has been shown to reflect impaired global cognition and attention deficits associated with AD. Our results suggest that P300 indices could be used as biological markers that indicate impaired neuropsychological functions in AD patients.

An aberrant protein complex in CSF as a biomarker of Alzheimer disease

To determine if an aberrant protein complex consisting of prostaglandin-d-synthase (PDS) and transthyretin (TTR) in CSF differentiates between subjects with Alzheimer disease (AD) and normal control (NC) subjects. Western blot analysis and a unique sandwich ELISA were used to quantify levels of complexed PDS/TTR in ventricular CSF of subjects with autopsy-verified diagnoses and in lumbar CSF of living subjects with mild to moderate probable AD and age-matched NC subjects. Ventricular CSF was obtained from short postmortem interval autopsies of 7 NC subjects (4 men/3 women), 12 diseased control (DC) subjects (7 men/5 women), 4 subjects with mild cognitive impairment (MCI) (2 men/2 women), and 8 subjects with late-stage AD (LAD) (4 men/4 women). Lumbar CSF was obtained from 15 subjects with probable AD (5 men/10 women) and 14 age-matched NC subjects (10 men/4 women) and was analyzed in a double-blind fashion. A significant increase in complexed PDS/TTR in ventricular CSF was found in MCI and LAD subjects but not DC subjects compared with NC subjects. Double-blind analysis of complexed PDS/TTR in lumbar CSF showed a significant sixfold increase in levels of the PDS/TTR complex in living probable AD subjects compared with age-matched NC subjects and a 100% sensitivity and 93% specificity in the identification of subjects with AD. After further study of larger numbers of patients, quantifying prostaglandin-d-synthase/transthyretin complex in CSF may be useful in the diagnosis of Alzheimer disease, possibly in the early stages of the disease.

Cerebral perfusion pattern of idiopathic normal pressure hydrocephalus studied by SPECT and statistical brain mapping

To investigate the specific pattern of cerebral blood flow (CBF) in subjects with idiopathic normal pressure hydrocephalus (iNPH) using voxel-based analysis. N-isopropyl-p-[123I]iodoamphetamine (IMP) single photon emission computed tomography (SPECT) images were performed in 30 iNPH patients, who met probable iNPH criteria, 30 Alzheimer disease (AD) patients and 15 normal control (NC) subjects. Inter-group comparisons between iNPH patients and NC subjects and between AD patients and NC subjects were performed using three-dimensional stereotactic surface projection (3D-SSP) analysis. Individual 3D-SSP images of the iNPH patients were assessed by visual inspection. On the Z-score maps, areas of relative hypoperfusion were recognized around the corpus callosum in all 30 iNPH patients, as well as in the Sylvian fissure regions in 19 of 30 iNPH patients which included artifacts by dilated ventricles and the Sylvian fissures. Ten frontal dominant, eight parietotemporal dominant, and 12 diffuse hypoperfusion types were demonstrated. Inter-group comparison between iNPH and NC subjects showed relative hypoperfusion in the frontal and parietotemporal areas and severe hypoperfusion around the corpus callosum and Sylvian fissure regions, while parietotemporal and posterior cingulate CBF reduction was demonstrated between the AD and NC groups. Voxel-based analysis showed a characteristic pattern of regional CBF reduction with frontal dominant or diffuse cerebral hypoperfusion accompanying severe hypoperfusion around the corpus callosum and Sylvian fissures with artifacts.

P.5.a.004 Validity of the Korean version of the Mini-Cog

The P300 is a useful psychophysiological index that reflects cognitive functions; however, the relationship between P300 indices and neuropsychological tests in Alzheimer's disease (AD) patients is unclear.Thirty-one AD patients and 31 elderly normal control (NC) subjects were recruited. Age and education level were matched between the two groups. The relationship between the P300 and the Korean version of the Consortium to Establish a Registry for Alzheimer's disease (CERAD-K) assessment packet (including 11 neuropsychological tests) was examined in AD patients.Compared to the NC subjects, the AD patients exhibited significantly decreased P300 amplitudes; however, there was no significant difference between the two groups in terms of P300 latency. After a permutation-based correction for multiple tests, P300 amplitudes at the Cz and Pz electrodes were significantly correlated with performance on the word list recognition, constructional praxis, and word fluency neuropsychological tests in the AD patients. Additionally, P300 latencies at the Pz and C6 electrodes were also significantly correlated with performance on the Mini-Mental State Examination, CERAD-K version (MMSE-K), and Trail Making Test part A (TMT-A) neuropsychological tests in the AD patients.The results suggest that the P300 is responsive to the deterioration of language, memory, and executive functions observed in AD patients. Although there was no significant difference between the AD patients and NC subjects in the P300 latency, P300 latency has been shown to reflect impaired global cognition and attention deficits associated with AD. Our results suggest that P300 indices could be used as biological markers that indicate impaired neuropsychological functions in AD patients.