HMPAO-SPECT Can Discriminate between Patients with Subjective Cognitive Complaints with and without Cognitive Deficits and those with Mild Cognitive Impairment.

BACKGROUND: Growing evidence suggests that pathological processes leading to Alzheimer's disease occurs gradually and begins to develop decades before the earliest clinical symptoms occur. The use of biomarkers has been proposed to detect evidence of preclinical Alzheimer's pathologic change in asymptomatic subjects. Subjective cognitive complaints (SCC) i.e. self-reported cognitive decline with normal cognition have been reported as an indicator of future cognitive decline, however, this condition is unspecific. OBJECTIVE: In the present study we used the regional brain perfusion measured by HMPAO-SPECT as Biomarker of neurodegeneration to compare the regional brain perfusion of patient with subjective cognitive complaints with and without minimal cognitive dysfunction (SCC+ and SCC- respectively) in respect to patients with mild cognitive impairment (MCI). METHODS: We retrospectively examined 736 Patients who referred to our Memory Clinic because of suspected cognitive dysfunction. After exclusion of patients with overt dementia, automated, quantitatively assessed relative cerebral blood flow of 10 forebrain regions (thalamus, parietotemporal, medial temporal, posterior temporal, posterior cingulate gyrus, each region left hemispheric and right hemispheric) and neuropsychological assessment of 64 SCC (32 SCC+; 32 SCC-) and 28 MCI subjects were analysed. RESULTS: .The most relevant differences between groups in cognitive performance concerned verbal memory. Left hemispheric medial temporal region could significantly discriminate between all three groups, with a progressive decrease n perfusion from SCC towards MCI. Area under the curve of left medial temporal region showed a sensitivity of 0,61 and a specificity of 0,78 for discriminating MCI from SCC. CONCLUSION: Automated analysis of HMPAO-SPECT data of MCI and SCC+ patients showed significant perfusion differences in medial temporal region and impaired verbal memory, both of which are known features of Alzheimer's disease. Perfusion patterns and verbal memory performance in SCC+ are more similar to MCI than SCC-. Thus, SPECT analysis could distinguish those subjects whose perfusion pattern resembles that of an MCI from those who do not. In our opinion, this could identify two populations with a different risk of progression to AD, with SCC+ subjects needing further diagnostic examination and repeated follow-up.

Cerebral perfusion (HMPAO-SPECT) in patients with depression with cognitive impairment versus those with mild cognitive impairment and dementia of Alzheimer's type: a semiquantitative and automated evaluation.

PURPOSE: Comparative evaluation of regional brain perfusion measured by HMPAO-SPECT of patients with mild cognitive impairment (MCI), dementia of Alzheimer's type (DAT) and depression with cognitive impairment (DCI). METHODS: A total of 736 patients were investigated because of suspected cognitive dysfunction. After exclusion of patients with other forms of dementia than DAT or relevant accompanying disorders, SPECT data from 149 MCI, 131 DAT and 127 DCI patients, and 123 controls without any cognitive impairment, were analysed. Relative cerebral blood flow of 34 anatomical regions was assessed with automated analysis software (BRASS). RESULTS: Calculation of global forebrain perfusion discriminated demented from nondemented patients. Compared to controls DCI patients showed hypoperfusion of the thalamus, lentiform nucleus and medial temporal cortex. MCI patients differed significantly from controls concerning perfusion in both hemispheric temporal and parietal areas, and in the (right hemispheric) posterior part of the cingulate gyrus. MCI and DCI patients differed in the parietal, temporal superior and right hemispheric cingulate gyrus posterior cortices. Global forebrain and regional perfusion was more extensively reduced in DAT patients and discriminated them from controls, and MCI and DCI patients. Frontal perfusion disturbance was only present in DAT patients. CONCLUSION: Automated analysis of HMPAO-SPECT data from MCI patients showed significant perfusion deficits in regions also involved in DAT patients, but ROC analysis demonstrated only moderate sensitivity and specificity for differentiating DAT patients from controls and DCI patients. Frontal hypoperfusion seems to correspond with conversion from MCI to DAT. Finally, the results in DCI patients again raise the question of depression as an early symptom of neurodegeneration.

Brain perfusion SPECT in patients with mild cognitive impairment and Alzheimer's disease: comparison of a semiquantitative and a visual evaluation.

Due to the increasing importance of early recognition and differential diagnosis of dementias, cerebral perfusion scans using "single photon emission computed tomography" (SPECT) are increasingly integrated into the examination routine. The goal of this study was to check the diagnostic validity of SPECT scans of MCI- and DAT-patients, two subgroups out of 369 persons with etiologically unclear cognitive dysfunction, which underwent an assessment program for probable dementia including cognitive testing, cranial computed tomography, ultrasound, routine laboratory testing including vascular risk factors. After exclusion of patients with no or other forms of dementia we analyzed SPECT data of patients with mild cognitive impairment (MCI; n = 85) and dementia of the Alzheimer type (DAT; n = 78) in comparison with a healthy control group (n = 34).Visual assessment as well as a manual "regions of interest" (ROI) regionalization of the cortex were performed, whereby a ROI/cerebellum ratio was calculated as a semi-quantitative value. Association cortex areas were assessed regarding frontal, temporal, and parietal lobes of both hemispheres. When comparing the ratios of patients with DAT and controls, we found a statistically significant reduction of the cerebral perfusion in all measured cortex areas (p < 0.001). The comparison of patients with MCI with the selected control group also established a statistically significant difference in the cerebral perfusion for the evaluated cortex areas with the exception of the left hemispheric frontal and parietal cortex.A considerable number of the MCI patients showed an MMSE-score within the normal range, but with regard to the perfusion in the right hemispheric association cortex these patients also could be distinguished unambiguously from controls. Sensitivity levels found by visual assessment were at least as high as those found by the ROI method (pathological assessment: visual 49.4% vs. ROI 47.1% for MCI; visual 75.6% vs. ROI 73.1% for DAT). High experienced visual assessment of cerebral perfusion scans using SPECT provides an useful additional tool in diagnosis of cognitive impairment. The used semiquantitative ROI-method is nearly equivalent and does not depend on the experience of the investigator.

Cognitive function and fMRI in patients with multiple sclerosis: evidence for compensatory cortical activation during an attention task.

Mild cognitive impairment has frequently been reported for patients in the early stages of multiple sclerosis. The aim of the present study was to measure whether altered cortical activation during a sustained attention task occurs along with limited extent of neuropsychological problems. Expanded brain activation of multiple sclerosis patients with normal motor function compared with healthy controls during a finger tapping paradigm has previously been reported. Compensatory brain activation in patients with multiple sclerosis compared with normal controls may also be observed when the subjects are performing cognitive functions. In 21 patients with clinically definite relapsing-remitting multiple sclerosis, a psychometric assessment was performed using the Wechsler Memory Scale (WMS) and the Multiple Sclerosis Functional Composite Score (MSFC). In addition, functional MRI was performed during a Paced Visual Serial Addition Task (PVSAT), a visual analogue of the Paced Auditory Serial Addition Task (PASAT). All patients were within 3 years of diagnosis and were not suffering from a relapse at the time of investigation. The multiple sclerosis patients were compared with a control group of 21 healthy volunteers matched for handedness, age, years of education and sex. With regard to psychometric results, the WMS general memory score showed statistically significant differences between patients and controls. We did not find differences for either the MSFC or the PASAT scores. A group analysis of the functional imaging data during the PVSAT revealed different activation patterns for patients compared with control subjects. In healthy volunteers, the main activation was found in the frontal part of the right gyrus cinguli (Brodmann area 32). In patients, the main activation was detected at the right hemispheric frontal cortex (Brodmann areas 6, 8 and 9). In addition, the left hemispheric Brodmann area 39 was activated. We interpret the different patterns of activation, accompanied with intact performance in a sustained attention task of our multiple sclerosis sample compared with healthy controls, as the consequence of compensatory mechanisms. This is an expression of neuronal plasticity during early stages of a chronic disease.

[Critical life events as risk factors for alcoholism]. / Kritische Lebensereignisse als Risikofaktoren des Alkoholismus.

There is some evidence for a relation between critical life-events and the excessive drinking of alcoholics; the present study fits well into the approach of life-event-research assuming an aggregation of life-events and difficulties to elicit or cause excessive drinking. In all 25 men who were in danger of becoming excessive drinkers and 29 who were not--all between 18 and 24 years of age--were asked for their life-events and difficulties within the past 5 years. The LES by G. Brown was used for assessment. The results showed clear evidence for the basic hypothesis of life-event-research; to account for this a 'model of an addictive threshold' is proposed. A qualitative analysis of the experienced difficulties and the way of coping throw some light on the nonspecificity of critical life-events within the stress model.