Functional imaging studies of episodic memory in Alzheimer's disease: a quantitative meta-analysis

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder, rapidly increasing in prevalence as the population ages. As the potential for disease-modifying therapy grows, a large body of literature has aimed at finding reliable, noninvasive biomarkers of AD, to allow for early intervention and sensitive tracking of therapeutic response. Task-related functional brain imaging techniques have been increasingly used to examine episodic memory function in AD. In the present study we completed a quantitative meta-analysis of this growing literature, to establish consensus and elucidate consistent patterns across this important research area. Results from encoding and retrieval paradigms were analyzed using the activation likelihood estimation (ALE) technique for patient and control groups. Second-level ALE analyses directly compared activation between these two groups. Results indicated a number of consistent findings across the included studies. Controls showed consistently greater activity than patients in a number of regions including the MTL and frontal pole across encoding and retrieval paradigms. Patients demonstrated increased activation likelihood in areas of the ventral lateral prefrontal cortex and other regions. Our findings quantitatively confirm the widely-cited deficits in MTL activity among AD patients, and also bring to light a pattern of differential prefrontal involvement, which may be implicated in compensatory changes occurring in AD. On the whole, this study quantitatively demonstrates that functional imaging studies show consistent, if complex, patterns of brain activation differences between patients and controls. These findings support the continued evaluation of functional neuroimaging for clinical use.