Background: Subjects with amnesic mild cognitive impairment (aMCI) may include patients at high risk for progression to Alzheimer disease (AD) and a population with different underlying pathologic conditions. Objective: To evaluate the potential roles of positron emission tomography with fluodeoxyglucose F 18 (18 FDG-PET) and memory scores in identifying subjects with aMCI and in predicting progression to dementia. Design, Setting, and Patients: Sixty-seven patients at European centers for neurologic and AD care who were diagnosed as having aMCI each underwent an extensive clinical and neuropsychological examination and an 18 FDG-PET study. Forty-eight subjects were followed up periodically for at least 1 year, and progression to dementia was evaluated. Main Outcome Measures: Brain glucose metabolism and memory scores. Results: Fourteen subjects with aMCI who converted to AD within 1 year showed bilateral hypometabolism in the inferior parietal, posterior cingulate, and medial temporal cortex. Subjects with "stable" aMCI presented with hypometabolism in the dorsolateral frontal cortex. The severity of memory impairment, as evaluated by the California Verbal Learning Test-Long Delay Free Recall scores, correlated with the following brain metabolic patterns: scores less than 7 were associated with a typical 18 FDG-PET AD pattern, and scores of 7 or higher were associated with hypometabolism in the dorsolateral frontal cortex and no progression to AD. Conclusion: These data provide evidence for clinical and functional heterogeneity among subjects with aMCI and suggest that 18 FDG-PET findings combined with memory scores may be useful in predicting short-term conversion to AD.
A kindred from South Tyrol (northern Italy) with familial, adult-onset parkinsonism of pseudo-dominant inheritance and mutations in the parkin gene was recently described. To gain insight into basal ganglia dysfunction in this form of hereditary parkinsonism, positron emission tomography (PET) with 18-fluorodopa (FDOPA) and 11C-raclopride (RAC) was performed in 5 affected family members and 5 asymptomatic relatives with proven compound heterozygous or heterozygous parkin mutations. Results were compared to findings in healthy control subjects and patients with typical sporadic, idiopathic Parkinson's disease. Similar to findings in the sporadic Parkinson's disease group, presynaptic striatal FDOPA storage was decreased in patients with compound heterozygous parkin mutations, with the most prominent reduction in the posterior part of the putamen. Along with the presynaptic lowered FDOPA uptake, we found a uniform reduction of the striatal 11C-raclopride binding index in all affected family members as compared to asymptomatic family members carrying a heterozygous parkin mutation, sporadic Parkinson's disease, and control subjects. Our PET data provide evidence that parkinsonism in this family is associated with presynaptic dopaminergic dysfunction similar to idiopathic Parkinson's disease pathophysiology, along with alterations at the postsynaptic D2 receptor level. In asymptomatic carriers of a single parkin mutation with an apparently normal allele, we found a mild but statistically significant decrease of mean FDOPA uptake compared to control subjects in all striatal regions. These data indicate a preclinical disease process in these subjects.
Objective: To study awareness of cognitive dysfunction in patients with very mild Alzheimer’s disease (AD) and subjects with mild cognitive impairment (MCI). Methods: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were ≧24 in all cases. The discrepancy between the patients’ and caregivers’ estimations of impairments was taken as a measure of anosognosia. Results: Self-reports of cognitive difficulties were comparable for AD and MCI patients. However, while in comparison to caregivers MCI patients reported significantly more cognitive impairment (p < 0.05), AD patients complained significantly less cognitive dysfunctions (p < 0.001). Conclusions: While most MCI patients tend to overestimate cognitive deficits when compared to their caregiver’s assessment, AD patients in early stages of disease underestimate cognitive dysfunctions. Anosognosia can thus be regarded as a characteristic symptom at a stage of very mild AD (MMSE ≧24) but not MCI. Accordingly, medical history even in mildly affected patients should always include information from both patient and caregiver.
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