Use of neuroimaging to detect early brain changes in people at genetic risk for Alzheimer's disease

Department of Psychiatry and Biobehavioral Sciences and the Center on Aging, University of California, Los Angeles School of Medicine, Los Angeles, CA, USA.
Advanced Drug Delivery Reviews (Impact Factor: 15.04). 01/2003; 54(12):1561-6. DOI: 10.1016/S0169-409X(02)00151-5
Source: PubMed


The neuropathological and cognitive changes preceding Alzheimer's disease appear to begin subtly decades before symptoms of the disease make the clinical diagnosis obvious. Clinical trials have begun to focus on preventive treatments designed to slow age-related cognitive decline and delay the onset of Alzheimer's disease in people with only mild memory complaints. Because people with few cognitive deficits represent a heterogeneous population, prevention studies require large samples in order to detect active drug effects. To address such challenges, recent neuroimaging studies have focused on middle-aged and older adults with only mild memory complaints and evaluated results according to the major known genetic risk for Alzheimer's disease, the apolipoprotein E-4 (APOE-4) allele. In studies using positron emission tomography during mental rest and functional magnetic resonance imaging during memory task performance, brain patterns differ according to genetic risk and are useful in predicting future decline measures and following disease progression in clinical trials.

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    • "None of the participants had a history of alcoholism, drug abuse, or evidence of neurological, medical, or psychiatric illness. From a total of 81 subjects who underwent SPECT, 23 subjects were selected for this analysis because they met the following inclusion criteria: (1) a CDR score of 0, (2) an estimated IQ of 120 or greater on the AMNART, (3) baseline scores on the BDS of less than 2, (4) a GDS score in the normal range (score , 11), (5) cognitive test scores within 1.5 SD from the mean on the basis of published test norms adjusted for age and education (see Table 1), and (6) two E3 alleles because E4 has been associated with increased risk for the development of AD and is also associated with regionally reduced cerebral metabolism (Caselli et al., 2004; Reiman et al., 2001, 2005; Small, 2002). We also excluded all subjects with an E2 allele as this allele has been linked to a reduced risk for AD (Hyman et al., 1996). "
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    ABSTRACT: Cognitive reserve among highly intelligent older individuals makes detection of early Alzheimer's disease (AD) difficult. We tested the hypothesis that mild memory impairment determined by IQ-adjusted norms is associated with single photon emission computed tomography (SPECT) perfusion abnormality at baseline and predictive of future decline. Twenty-three subjects with a Clinical Dementia Rating (CDR) score of 0, were reclassified after scores were adjusted for IQ into two groups, 10 as having mild memory impairments for ability (IQ-MI) and 13 as memory-normal (IQ-MN). Subjects underwent cognitive and functional assessments at baseline and annual follow-up for 3 years. Perfusion SPECT was acquired at baseline. At follow-up, the IQ-MI subjects demonstrated decline in memory, visuospatial processing, and phonemic fluency, and 6 of 10 had progressed to a CDR of 0.5, while the IQ-MN subjects did not show decline. The IQ-MI group had significantly lower perfusion than the IQ-MN group in parietal/precuneus, temporal, and opercular frontal regions. In contrast, higher perfusion was observed in IQ-MI compared with IQ-MN in the left medial frontal and rostral anterior cingulate regions. IQ-adjusted memory impairment in individuals with high cognitive reserve is associated with baseline SPECT abnormality in a pattern consistent with prodromal AD and predicts subsequent cognitive and functional decline.
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    • "However, even with similar performance, the age-related difference in the neural substrates between the forward recall and the backward recall may be detected with fMRI, as shown in this study. Other researchers have suggested that fMRI may be more sensitive than behavioral measurements (Hariri and Weinberger, 2003; Honey and Bullmore, 2004; Honey et al., 2004; Mattay and Goldberg, 2004; Wilkinson and Halligan, 2004), and fMRI has been used to investigate the biological basis of aging and dementia (Anderson and Grady, 2001; Buckner, 2004; Hedden and Gabrieli, 2004) and its use has been explored for the early detection of dementia (Bookheimer et al., 2000; Small, 2002). Thus, the paradigm used in the present study may have potential clinical applications as well. "
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