The clinical phenotype of early dementia

• Main Author: Ahmed, S.
• Published: University of Cambridge 2008
• Subjects: 616.8
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.595383

Amnestic MCI (aMCI) is defined as a transitional stage in the development of dementia proper, with the most likely outcome being AD. This thesis endeavours to contribute to further clarification of the clinical signature of aMCI in a series of neuropsychological investigations based on the central memory disturbance. In the first stage of investigation, the nature of the subjective memory impairment was explored. An analysis based on a comprehensive questionnaire showed that memory complaints are common in clinical practice. The nature of these complaints showed that aMCI patients could not be separated from a ‘worried well’ group, although semantic dementia patients exhibited a clearly different profile. This highlights the necessity of objective assessment to corroborate memory complaints. The second stage of investigation explored the criterion for objective episodic memory impairment in aMCI. Addressing the purity of this deficit, tasks of object, people and face knowledge were used to probe for semantic memory impairment. The results showed that aMCI patients showed robust deficits compared to controls in these tests. Next, we looked into whether the episodic memory impairment could be reliably and robustly detected by probing associative learning memory. A key aspect of episodic memories is the rapid association of fragments into a coherent memory trace, which demands competence in associative learning. Based on work initiated in Cambridge, the nature of visuospatial associative learning impairment in aMCI was explored comparing the binding of novel and familiar stimuli. Recall was lower for the novel stimuli than for the familiar indicating a more sensitive task, since each element was new and required more encoding. Further, the prognostic utility of associative learning in combination with a measure of global cognition showed high sensitivity and specificity in predicting rapid progression to AD. Finally, we explored the utility of the associative learning deficit for differential diagnosis of early dementia. Differentiation of behavioural variant frontotemporal dementia (bvFTD) and AD has proved particularly difficult because of clinically overlapping symptoms. Compared to aMCI, bvFTD patients performed better overall, but inconsistently, on associative learning tasks suggesting that some bvFTD patients have subtle memory deficits. Still, associative learning may be a useful tool by which to explore differential diagnosis.