Mild cognitive impairment neuroimaging markers for early diagnosis of dementia

University dissertation from Stockholm : Karolinska Institutet, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research (NEUROTEC)

Abstract: This thesis concerns the investigation of mild cognitive impairment (MCI) and Alzheimer's disease (AD) using single photon emission computed tomography (SPECT) and quantitative electroencepholography (qEEG). In study I, The qEEG values were cross-sectionally compared between AD, MCI and controls. AD had decreased global field power (GFP) and more anterior localization of three-dimensional dipole source in alpha and beta frequency. The results of longitudinal investigation of MCI showed a decreased alpha GFP and a more anterior localization of sources of theta, alpha and beta frequency in progressive mild cognitive impairment (PMCI), as compared to non-progressive mild cognitive impairment (SMCI). EEG values showed a moderate diagnostic accuracy in the study of AD and MCI. In study II & III, the baseline regional cerebral blood flow (rCBF) and neuropsychology were investigated in PMCI and SMCI. PMCI had decreased regional cerebral blood flow (rCBF) in posterior cingulate and parietal lobe as well as increased brain perfusion in prefrontal cortex compared to SMCI at baseline. The cognitive functions of PMCI were lower than SMCI with respect to episodic memory, visuospatial and general cognitive function represented by Mini-Mental State Examination (MMSE). Both SPECT and Neuropsychological test had moderate discriminant function between PMCI and SMCI at baseline and combining two methods can improve the diagnostic accuracy. In study IV, the longitudinal rCBF changes of PMCI and SMCI were investigated. SPECT data were analyzed with statistical parametric mapping (SPM) and BRASS program. No significant findings were detected using SPM. The results of BRASS showed a significant rCBF longitudinal reduction of PMCI in superior parietal lobe, parieto-temporal association cortex and medial temporal lobe and a significantly decreased general cognitive function represented by MMSE. To summarize, SPECT and EEG could provide promising markers for the early diagnosis of dementia and track the disease progression. Combining imaging investigation with neuropsychological testing may increase the diagnostic accuracy of preclinical dementia.

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