Dannhauser, T.M.; (2011) Functional MRI studies of memory, attention and treatment response in prodromal Alzheimer’s Disease. Doctoral thesis , UCL (University College London).

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Abstract

BACKGROUND: Alzheimer's disease (AD) is characterised by initial episodic amnesia followed by deficits in divided attention. Amnestic mild cognitive impairment (AMCI), considered prodromal for AD, is characterised by isolated amnesia but attentional deficits have also been observed. Amnesia in AD is ascribed to medial temporal lobe pathology; however, attention deficits are likely due to lesions in other areas that demonstrate early AD neuropathology e.g. prefrontal cortex and basal forebrain cholinergic system. These lesions could contribute to episodic amnesia and causes attention deficits in prodromal AD. Acetylcholinesterase inhibitor drugs are used as treatment in AD and their effects on memory and attention remain to be determined in AMCI. METHODS: Functional magnetic resonance imaging (fMRI) was used to study divided and selective attention, and verbal episodic memory in AMCI (n=20) by comparison to controls (n=10). AMCI were followed to identify those that progressed to AD. A controlled treatment trial was conducted to study the effects of the acetylcholinesterase inhibitor rivastigmine. RESULTS: The AMCI sample had a high rate of progression to AD (n=12). AMCI demonstrated slower reaction times and altered cortical activation during divided attention. Reaction times correlated inversely with default mode network activation. Cortical activation was altered during selective attention. Verbal amnesia was associated with semantic deficits that correlated with altered cortical activation. Rivastigmine improved reaction times on divided attention but did not affect memory. CONCLUSIONS: Divided attention is impaired and selective attention processing altered in prodromal AD. Verbal amnesia appears partly related to executive failure. Furthermore, correlations between memory and attention deficits suggest that executive failure contributes to deficits across cognitive domains in prodromal AD. Activation changes in prodromal AD during memory and attention processing suggest impaired regulation and failure of cortical resources. Rivastigmine improves divided attention via enhanced cortical processing but it does not benefit verbal episodic memory.

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