Vincent I. H. Kwa

Predicting Survival in Patients with Early Alzheimer’s Disease

We investigated whether an index based on clinical features, electroencephalogram and computed tomography is useful to predict survival in early Alzheimer’s disease. One hundred and sixty-three consecutively referred patients to an outpatient memory clinic and first diagnosed with Alzheimer’s disease (105 ‘probable’ and 58 ‘possible’, NINCDS-ADRDA criteria) were studied and outcome measure was death. Cox proportional hazards regression analysis and Kaplan-Meier survival curves were used to investigate relations between baseline parameters and survival. Eighty-four patients (51.5%) died during the follow-up period that extended to 5.8 years, with a median duration of survival after entry of 4.3 years. Baseline factors that were statistically significant and independently related to increased risk of mortality were high age, male sex, poor cognitive function as measured with the CAMCOG, low alpha and beta power on electroencephalogram, and temporoparietal atrophy on computed tomography scan. These results were independent of the diagnosis probable or possible Alzheimer’s disease. Based on the coefficients from the regression equation, we computed a survival index for each patient and we constructed three groups according to tertiles of this index. After 5.2 years of follow-up, survival curves showed a low mortality group with 81.7% patients alive (median survival at least 5.7 years), an intermediate mortality group with 35.9% patients alive (median survival 3.8 years), and a high mortality group with no patients alive (median survival 2.3 years). Log rank tests were statistically significant for comparisons between all three groups. We conclude that an overall index combining demographic, cognitive, electroencephalogram and computed tomography features is a strong predictor of survival in early Alzheimer’s disease.

Spectral analysis of the EEG and 99m-Tc-HMPAO SPECT-scan in Alzheimer's disease

99m-technetium-hexamethylpropylene-amineoxine (99m-Tc-HMPAO) single-photon-emission-computer-tomography (SPECT)-scans and spectral analyzed electroencephalogram (EEGs) of 20 patients with Alzheimers disease (AD) were studied. A significant correlation was found between the temporoparietal-cerebellar-ratio (TP/C-ratio) of the SPECT-scan and the peak frequencies of leads T3-T5, C3-P3, and C4-P4 of the EEG. In addition a significant negative correlation between the TP/C-ratio and the theta/alpha-ratio (t/a-ratio) of leads T3-T5, T4-T6, C3-P3, and C4-P4 was demonstrated. Our study demonstrates that slowing of the EEG parallels a decrease in blood flow in the temporoparietal regions in AD-patients. Both findings could be parallel phenomena of regional hypometabolism.

Determinants of Quantitative Spectral Electroencephalography in Early Alzheimer’s Disease: Cognitive Function, Regional Cerebral Blood Flow, and Computed Tomography

Electroencephalography (EEG) bands may have different clinical or physiological correlates at initial diagnosis of Alzheimer’s disease (AD). We studied 163 consecutive patients with probable (n = 105) and possible (n = 58) AD with measurements of cognitive function (CAMCOG), regional cerebral blood flow (rCBF) with single photon emission computed tomography using technetium-99m-labeled hexamethylpropylene amine oxime, and computed tomography (CT). Lower CAMCOG scores were significantly and most strongly associated with lower parieto-occipital and fronto-central alpha power. In a separate analysis of cognitive domains, disturbances in language, praxis, attention, and abstraction were also significantly and most consistently related to decrease in alpha power. Presence of cortical atrophy as measured on CT showed some statistically significant relations with EEG bands, but these associations were not consistent. Lower temporal and parietal rCBF were significantly related to lower parieto-occipital alpha activity. Presence of leukoaraiosis was significantly associated with lower beta values, but also with higher absolute theta and delta activity. The results suggest that alpha on EEG is most closely linked to cognitive function and rCBF, while beta and theta activity more likely reflect lower cortical or subcortical changes. Our study thus provides evidence that the EEG bands reflect differential pathophysiologic changes in AD.

T2-Weighted Hyperintense MRI Lesions in the Pons in Patients With Atherosclerosis

BACKGROUND AND PURPOSE Pontine hyperintense lesions (PHL) on T2-weighted MRI have been recognized recently. Histopathological findings resemble periventricular leukoaraiosis, and a vascular etiology has been suggested. We studied the frequency and the associated factors of PHL in patients with symptomatic atherosclerosis. METHODS Two independent observers assessed brain MRIs in a prospective cohort of patients with symptomatic atherosclerosis. Only patients in whom both observers scored PHL on T2- and proton density-weighted images, but not on T1-weighted images, were considered to have the lesion. RESULTS We studied 229 patients 31% presenting with ischemic stroke, 31% with myocardial infarction, and 38% with peripheral artery disease. Both observers scored PHL in 23% of all patients. Patients with PHL were significantly older and had more lacunar infarcts and periventricular leukoaraiosis than patients without PHL. There were more women, more hypercholesterolemic and diabetic patients, and more cortical infarcts on MRI (P = NS). After logistic regression the presence of leukoaraiosis (odds ratio, 2.4; 95% confidence interval, 1.6 to 3.4) and lacunar infarcts (odds ratio, 2.2, 95% confidence interval, 1.5 to 3.1) remained independently associated with PHL. PHL was more common in patients with ischemic strokes (39%) than in patients with myocardial infarctions (11%) or peripheral artery disease (19%) (P < .001). CONCLUSIONS We found that PHL on T2- and proton density-weighted MR images are often found in patients with symptomatic atherosclerosis. The association with periventricular leukoaraiosis and lacunar infarcts suggests that PHL is a variant of leukoaraiosis, with possibly the same pathophysiology. The clinical symptoms and consequences of PHL, however, are not yet clear.

Feasibility of cognitive screening of patients with ischaemic stroke using the CAMCOG A hospital-based study

Brief screening tests would be convenient for the measurement of cognitive impairment in stroke patients. In these patients aphasia can interfere with test procedures. To evaluate the feasibility of examining cognitive functions in stroke patients we examined 129 patients with an ischaemic stroke using the CAMCOG, a standardised neuropsychological screening test, after an interval of at least 3 months. Most patients (88%) were able to complete the CAMCOG. Patients with severe aphasia were significantly more likely to have an abnormal CAMCOG score than patients without aphasia [relative risk (RR) 4.0, 95% confidence interval (CI) 2.8–5.8]. The group of patients with moderate aphasia was not at higher risk of having an abnormal CAMCOG score than patients without aphasia (RR 1.4, 95% CI 0.6–2.8). Looking for other factors that might correlate with the scores, logistic regression analysis revealed age as the only significant factor for the prediction of the CAMCOG score (odds ratio 4.0, 95% CI 1.2–13.2). We concluded that the CAMCOG can conveniently be used for screening cognitive functions in patients with cerebral infarcts, even if there is moderate aphasia.

Epidermal nevus syndrome with isolated enlargement of one temporal lobe: a case report

A 5-month-old girl presented with infantile spasms and psychomotor retardation. She was born with epidermal nevi on the right side of the head, the right arm and the back. MRI of the head showed a right hemimegalencephaly limited to the temporal lobe. There were no MRI signs of neocortical dysplasia. Ultrasonography revealed multiple cysts in both ovaria and a small solid lesion in the left adrenal gland. Hemimegalencephaly represents an overgrowth phenomenon; the isolated temporal lobe hypertrophy can be explained as a mild expression of hemimegalencephaly. To our knowledge this has not been described before.