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PET correlates of cognition deficits in Alzheimer’ disease

rather similar to word list recall test score correlation indicating a potential frontal network of delayed episodic memory function independent of stimulus quality.

According to our findings, neuropsychological deficits in

AD do not refer to discrete changes in a particular area or hemisphere but are associated with a pattern of changes involving different sites. Specific and predictable relation- ships arose between regional brain metabolism (left and right, frontal, temporal, and parietal lobes) and the neurop- sychological measures of verbal fluency, constructional praxis, and verbal list learning.45 On tests of verbal fluency and naming, correlations primarily involved the left hemi- sphere while constructive praxis recall was solely correlated with right hemispheric changes. Our study demonstrates the expected relationships between neuropsychological deficits and regional cerebral metabolic changes and corresponds to earlier findings of Welsh and colleagues, who investigated CERAD subscores with visual ratings of PET scans in predefined regions of interest in 66 patients with various dementias such as AD, vascular dementia, Pick’s disease, or atypical progressive dementia.46 Our findings are in accor- dance withNobili et al. who found an association between the performance of a verbal memory test and the cerebral activation in parietal and left hippocampal cortices using single photon emission computed tomography (SPECT).47

Lacking a sufficient follow-up period, results of the present

study are limited and warrant further investigation. However, since conversion rates to dementia are expected to be about 15% per year among MCI patients, the follow-up period has to be chosen carefully depending on age and character of the cohort. In further studies, amnestic MCI patients may be investigated separately from nonamnestic MCI, which could not be done in the present study where the vast majority of patients suffered from amnestic deficits. Partial volume effects due to sulcal atrophy in AD and the ability of patients to execute the CERAD test battery need to be discussed as potential confounding variables. Partial volume effects were minimized by the high spatial resolution capacity of the PET imaging technique. That atrophic change has only minor effects on regional glucose uptake in the patients with MCI and mild AD investigated here is further corroborated by a previous study of our group.9 All the 75 patients included in the study collaborated in all study procedures and completed the CERAD test battery, demonstrating their comprehension and ability to perform the test.Otherwise, the resulting profiles of the neuropsychological testing paralleled those identified in a larger patient sample.6

In conclusion, results of our study provide further evidence

that not only memory function but also functions of language and constructional praxis involve subsets of uni- and bilateral brain areas in patients with AD and its potential preclinical stages. Compared to scores of immediate memory perfor- mance, delayed memory test performance showed an addi- tional correlation with frontal association cortices indicating a network of brain regions involved in delayed episodic memory and supporting the CERAD battery as a valid measure in the clinical evaluation. 7

Acknowledgements: The authors thank S. Jost, PhD, and E. Ahlsdorf, PhD, for technical assistance.

Disclosure: Dr. Peter Scho ¨enknecht is the principal investigator of

this report. He receives honoraria from Novartis Pharma & Janssen Cilag.


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¨der J. Distribution of cerebral

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