A SPECT study of sleep disturbance and Alzheimer's disease.

BACKGROUND/AIMS: This study aimed to investigate the possible association of regional cerebral perfusion and sleep loss in Alzheimer's disease (AD). METHODS: 55 AD patients were characterized as having (SL) or not having (NSL) nocturnal sleep loss based on standard AD scales assessing sleep over the previous 4 weeks. (99m)Tc-ethylcysteinate dimer SPECT scans were performed in a relaxed, wakeful state. Whole-brain analysis using Statistical Parametrical Mapping (SPM5) was performed to compare perfusion across groups. In addition, the AD groups were compared to normal control (NC) subjects of comparable age and gender to provide a context for interpretation of findings. RESULTS: SPM analysis showed increased perfusion in the right middle frontal gyrus (R-MFG, Brodman area 9, p = 0.016, familywise-error-corrected) in SL versus NSL patients. Comparison with NC subjects confirmed that perfusion in the R-MFG among SL patients did not exceed that found in NCs (relative rather than absolute hyperperfusion). CONCLUSIONS: In this sample of mild-to-moderate AD patients, relative hyperperfusion in the R-MFG is associated with reports of SL. This region may play a role in regulating sleep.

Linear width of the medial temporal lobe can discriminate Alzheimer's disease from normal aging: the Sunnybrook dementia study.

To discriminate Alzheimer's disease (AD) from healthy controls, the thinnest medial temporal lobe (tMTL) width on 3D-MRI was measured according to a newly developed method at the inter-collicular sulcus (ICS) level with scans aligned to the long axis of the hippocampus in 22 mild, 27 moderate probable AD patients and 41 healthy controls. For comparison, MTL width replicating the technique of Jobst et al. (jMTL) as well as hippocampal and parahippocampal volumes, were also measured. Using logistic regression taking into account age, sex, and education, tMTL width classified mild AD from controls with a sensitivity of 86%, specificity of 95% and accuracy of 92%. Similar values were obtained for moderate or total AD group versus controls. By comparison, jMTL width was only useful in distinguishing moderate AD from controls, and volumetric measures were equally sensitive in classifying mild and moderate AD in our sample. This quick, reliable, and standardized measurement of tMTL can be helpful in differentiating even mild AD from controls with reasonable accuracy.

A reliable MR measurement of medial temporal lobe width from the Sunnybrook Dementia Study.

We studied the hippocampal angle and spatial relationships of medial temporal lobe (MTL) structures, using midbrain colliculi and inter-collicular sulcus (ICS) as landmarks, and measured MTL width on axial 3D-T1-weighted MRI at ICS level in 41 normal, aged participants. Mean hippocampal angle was 29 degrees (range 17-42 degrees ) caudal to the anterior-posterior commissure (AC-PC) line. The slice at the ICS, parallel to the long axis of the hippocampus, best revealed a longitudinal view of hippocampus and parahippocampal gyrus in 76% of participants, compared to only 7% when slices were 20 degrees caudal to orbitomeatal line (OML), an accepted technique used to examine MTL width in previous CT studies. The MTL width measured midway and at its thinnest between the anterior-posterior borders of the midbrain was highly reproducible (intraclass correlation coefficients >0.98) using these new methods. These simple decision rules, individualized orientation along the hippocampus and using a standardized landmark like the ICS, make these measures more comparable across subjects, and hence more useful in detecting and monitoring MTL atrophy in dementia.

Functional and neuroanatomic correlations in poststroke depression: the Sunnybrook Stroke Study.

BACKGROUND AND PURPOSE: The purpose of our study was to determine the functional and neuroanatomic correlates of poststroke depressive symptoms. METHODS: Patients with consecutive admissions to a regional stroke center for new-onset unilateral hemispheric stroke who met World Health Organization and National Institute of Neurological and Communicative Disorders and Stroke criteria were eligible for inclusion in a longitudinal study. Acutely, patients underwent CT scanning, and at 3 months and 1 year after stroke, depressive symptoms were assessed by using both the Montgomery-Asberg Depression Rating Scale and the Zung Self-Rating Depression Scale. The Functional Independence Measure (FIM) served as an indication of functional outcome and was obtained at 1 month, 3 months, and 1 year after stroke, along with other demographic information. The Talairach and Tournoux stereotactic atlas was used for the primary determination of CT lesion localization. Lesion proximity to the anterior frontal pole was also measured. RESULTS: Eighty-one patients participated in the longitudinal study. Stepwise linear regression analyses generated a highly significant model (F(3,76)=9.8, R(2)=28%, P<0.0005), with lower 1-month total FIM scores, living at home, and damage to the inferior frontal region predicting higher depression scores at 3 months. Similarly, lower 3-month total FIM scores correlated with higher 3-month depression scores, and lower 1-year total FIM scores correlated with higher 1-year depression scores. CONCLUSIONS: Functional measures correlated with poststroke depression across time and, together with neuroanatomic measures, predicted depressive symptoms longitudinally. Although inferior frontal lesion location, irrespective of side, appeared to play a role as a risk factor in this study, the degree of functional dependence after stroke imparted the greatest risk.

Three brain SPECT region-of-interest templates in elderly people: normative values, hemispheric asymmetries, and a comparison of single- and multihead cameras.

UNLABELLED: The purpose of this study was to generate anatomically guided region-of-interest (ROI) brain SPECT templates based on scans of elderly healthy volunteers. We describe normal tracer uptake and hemispheric asymmetries for each of 3 camera systems and compare these characteristics among systems. METHODS: 99mTc-hexamethyl propyleneamine oxime SPECT scans were acquired from 28 elderly healthy volunteers (mean age [+/-SD], 70.3 +/- 6.5 y) on a single-head rotating gamma camera (n = 15) or on dual- (n = 18) or triple-head (n = 13) cameras. The average number of counts in each ROI was calculated and referenced to counts in a cerebellar ROI, providing semiquantitative regional cerebral blood flow (rCBF) ratios. For the templates and ROI map, base images of a healthy volunteer were obtained with each camera. Data from individuals scanned with 2 cameras on the same day (n = 15) were used to evaluate rCBF differences across cameras. For each camera, averaged SPECT templates were made using automated image registration. The base volunteer's T1-weighted MR image was converted to stereotactic space with dimensions similar to those of the SPECT templates, and 79 bilateral ROIs were defined. To obtain ROI rCBF ratios, we aligned individual images to their appropriate template and then to this modified MR image. RESULTS: The ROI coefficients of variation indicated that the fit of the ROIs was acceptable (0.07-0.35). Mean rCBF ratios ranged from 0.57 to 1.0, 0.67 to 1.01, and 0.63 to 1.00 for single-, dual-, and triple-head cameras, respectively. The cuneus, occipital cortex, occipital pole, middle temporal gyrus, and posterior middle frontal gyrus showed consistent hemispheric asymmetry (right side greater than left side in 83%-100% of individuals). Mean rCBF ratios did not differ between dual- and triple-head cameras, whereas the ratios for single- and dual-head cameras differed significantly (39 ROIs differed), even after smoothing and filtering the dual-head images to the level of the single-head images. CONCLUSION: The use of SPECT templates based on elderly healthy volunteers is an important feature of this technique because most available templates have used young individuals. Another important feature is the use of MR image-based ROIs. These procedures are versatile because they use more than 1 camera. They can easily be implemented in clinical and research settings to detect camera-specific, abnormal deviations in rCBF ROI ratios and asymmetry magnitudes in diseases associated with aging, such as stroke and dementia.

Brain SPECT imaging and left hemispatial neglect covaried using partial least squares: the Sunnybrook Stroke study.

Hemispatial neglect, characterized as failure to attend to contralesional space, is hypothesized by current neuroanatomical models to result from damage to a network involving the frontal, parietal, and cingulate cortices, basal ganglia, and thalamus. This study investigated this model of neglect in 81 right hemisphere-damaged acute stroke patients using 99mTc-HMPAO single photon emission-computed tomography (SPECT). In order to exploit the inherent collinearity of SPECT regional brain ratios, a novel statistical technique, partial least squares (PLS), was utilized. It makes use of high correlations to identify biologically relevant patterns of brain activity. Averaged ipsilesional cerebellar ratios from 152 brain segments were covaried with performance on subtests of the Sunnybrook Neglect Battery. In this patient sample, the most influential region identified by PLS corresponded to the area surrounding the right temporal-parietal-occipital (TPO) junction that included the right lateral occipital, temporal, and inferior parietal lobes. Hypoperfusion in the medial frontal cortex, including the anterior cingulate, also emerged as significantly associated with more severe neglect. Thus, hypoperfusion in only two of the five hypothesized network regions emerged as significantly associated with hemispatial neglect on SPECT imaging. This work converges with structural imaging studies to suggest that damage to the TPO junction, not just the parietal lobe, may be the critical region for hemispatial neglect. Our study demonstrated the utility of PLS for analyzing functional imaging and behavioral data sets in a clinical population in relation to current neuroanatomical models of neglect.

Brain-behavior correlations in hemispatial neglect using CT and SPECT: the Sunnybrook Stroke Study.

OBJECTIVE: Structural and functional lesion localization in patients with hemispatial neglect. DESIGN: Location and severity of brain damage on CT and SPECT correlated with neglect performance as assessed with a battery of drawings, line bisection, and line and shape cancellation subtests. PATIENTS: Participants included 120 consecutive stroke patients with a single right-hemisphere-damaged lesion on CT who were admitted to the Acute Stroke Care Unit at Sunnybrook Health Science Centre. Of these, 88 also had a SPECT. RESULTS: On CT, 82 patients with neglect (compared with 38 without neglect) had more extensive damage in the parietal and sensorimotor cortex and white matter fiber bundles, including the posterior-superior longitudinal and inferior-frontal fasciculi (p < 0.05). Parietal and anterior cingulate damage best predicted neglect score using the CT data (p < 0.05), and regional blood flow in the parietal cortex best predicted neglect score using the SPECT data (p < 0.05) after controlling for the influence of age and lesion size on multiple linear regression. CONCLUSIONS: Damage in the parietal and anterior cingulate cortex and posterior white matter fiber bundles correlated with hemispatial neglect. Combining structural- and functional-imaging techniques with neurobehavioral analysis can elucidate brain-behavior relationships.