FDDNP-PET scanning can differentiate persons with mild cognitive impairment from those with Alzheimer's disease and those with no cognitive impairment. This technique is potentially useful as a noninvasive method to determine regional cerebral patterns of amyloid plaques and tau neurofibrillary tangles.

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The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by using positron emission tomography in middle-aged and older nondemented persons with normal memory performance. A single copy of the APOE-4 allele was associated with lowered inferior parietal, lateral temporal, and posterior cingulate metabolism, which predicted cognitive decline after 2 years of longitudinal follow-up. For the 20 nondemented subjects followed longitudinally, memory performance scores did not decline significantly, but cortical metabolic rates did. In APOE-4 carriers, a 4% left posterior cingulate metabolic decline was observed, and inferior parietal and lateral temporal regions demonstrated the greatest magnitude (5%) of metabolic decline after 2 years. These results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments.apolipoprotein E ͉ positron emission tomography ͉ cerebral glucose metabolism ͉ age-associated memory impairment A lzheimer's disease (AD) accounts for approximately twothirds of late-life dementias, afflicting an estimated 8% of people age 65 years and older (1). In the United States alone, AD victims total nearly four million, and annual cost estimates, including caregiver productivity losses and costs of medical, long-term, and home care, approach $90 billion (2, 3). The disease's gradual decline in memory, other cognitive functions, behaviors, and daily functions progress until patients eventually require total care from others (4).Mild memory complaints build gradually years before patients develop dementia, and neurofibrillary tangles (5) and neuritic plaques (6), the neuropathological hallmarks of AD, are present in older persons with memory complaints too mild to warrant a diagnosis of dementia. Amyloid deposits have been observed in middle-aged nondemented persons decades before they reach the age at risk for late-onset AD (7). Moreover, diffuse plaques in nondemented elderly persons are associated with an accelerated age-related cortical cholinergic deficit, which could represent a clinical stage preceding dementia (8). Such observations have stimulated interest in ''preclinical'' AD markers aimed at identifying candidates who may benefit from novel antidementia treatments. Randomized, placebo-controlled trials of cholinesterase inhibitors, anti-oxidants, and anti-inflammatory agents are already in progress for such conditions as mild cognitive impairment (9) or age-associated memory impairment (AAMI) (10). These experimental drug trials use standard clinical examination methods to identify subjects and follow cognitive decline (4, 11). Because many people with mild memory c...

BACKGROUND Multiple lines of evidence indicate a strong genetic contribution to autism spectrum disorders (ASDs). Current guidelines for clinical genetic testing recommend a G-banded karyotype to detect chromosomal abnormalities and fragile X DNA testing, but guidelines for chromosomal microarray analysis have not been established. PATIENTS AND METHODS A cohort of 933 patients received clinical genetic testing for a diagnosis of ASD between January 2006 and December 2008. Clinical genetic testing included G-banded karyotype, fragile X testing, and chromosomal microarray (CMA) to test for submicroscopic genomic deletions and duplications. Diagnostic yield of clinically significant genetic changes was compared. RESULTS Karyotype yielded abnormal results in 19 of 852 patients (2.23% [95% confidence interval (CI): 1.73%–2.73%]), fragile X testing was abnormal in 4 of 861 (0.46% [95% CI: 0.36%–0.56%]), and CMA identified deletions or duplications in 154 of 848 patients (18.2% [95% CI: 14.76%–21.64%]). CMA results for 59 of 848 patients (7.0% [95% CI: 5.5%–8.5%]) were considered abnormal, which includes variants associated with known genomic disorders or variants of possible significance. CMA results were normal in 10 of 852 patients (1.2%) with abnormal karyotype due to balanced rearrangements or unidentified marker chromosome. CMA with whole-genome coverage and CMA with targeted genomic regions detected clinically relevant copy-number changesin7.3%(51 of 697) and 5.3%(8 of 151) of patients, respectively, both higher than karyotype. With the exception of recurrent deletion and duplication of chromosome 16p11.2 and 15q13.2q13.3, most copy-number changes were unique or identified in only a small subset of patients. CONCLUSIONS CMA had the highest detection rate among clinically available genetic tests for patients with ASD. Interpretation of microarray data is complicated by the presence of both novel and recurrent copy-number variants of unknown significance. Despite these limitations, CMA should be considered as part of the initial diagnostic evaluation of patients with ASD.