SUMMARYObjective Subjective cognitive impairment (SCI) has been proposed as a clinical stage which may precede mild cognitive impairment in the clinical continuum of AD, and is characterised by the presence of subjective memory complaints in the absence of objective cognitive deficits. Specific memory-related brain activation differences have been reported in mild cognitive impairment and in cognitively normal individuals at known genetic risk of AD; our objective was to determine whether similar differences are present in people with SCI. Methods We compared brain activation in a memory clinic sample of 10 SCI subjects and 10 controls during a verbal episodic memory encoding task using functional magnetic resonance imaging (fMRI). Results There were no differences between groups on measures of encoding success (recognition accuracy) nor was there evidence of altered semantic processing. Both groups activated left prefrontal cortex (PFC) and cerebellum during encoding. The SCI group also demonstrated activation in left medial temporal, occipitoparietal and medial frontal cortex. Group comparisons revealed increased activation in SCI in left PFC, where activation strength correlated with memory task performance. Conclusions The activation differences reported in this study may reflect the employment of compensatory strategies in the face of early AD pathology, although a number of alternative explanations need to be considered. Further studies with larger samples may help to determine whether the observed activation changes are likely to be associated with early neuropathological processes or with other unrelated factors.

Recent neuroimaging studies have demonstrated changes in brain function in cognitively normal subjects at increased risk of developing Alzheimer's disease. Amnestic mild cognitive impairment (AMCI) carries a high risk of developing into Alzheimer's disease. In AMCI altered cortical activation has been demonstrated during memory tasks, using functional MRI (fMRI). Memory and attention are closely related cognitive functions. It is unclear whether the memory impairment of AMCI is associated with attentional deficits of the sort likely to be revealed by tasks requiring divided attention. Ten older adults (mean age 72 years, range 57-81 years) with AMCI were compared with healthy matched controls on divided attention and passive sensory processing tasks using fMRI. During the divided attention task both groups activated similar regions of left hemispheric prefrontal and extrastriate visual cortex. However, the AMCI group had attenuated prefrontal activation compared with age matched controls. On the passive sensory processing task there was no difference between the AMCI and control groups. We conclude that there are changes in the functional network subserving divided attention in patients with AMCI as reflected in the attenuation of prefrontal cortical activation. These findings have implications for evaluating cognition in AMCI and also for monitoring the effects of future treatments in AMCI.

This pattern of increased activation is similar to the pattern of decreased activation reported during divided attention in AD and may indicate compensatory changes. These findings suggest the presence of early functional changes in SCI; longitudinal studies will help to further elucidate the relationship between SCI and AD.

BackgroundDementia affects 35 million people worldwide and is currently incurable. Many cases may be preventable because regular participation in physical, mental and social leisure activities during middle age is associated with up to 47% dementia risk reduction. However, the majority of middle-aged adults are not active enough. MCI is therefore a clear target for activity interventions aimed at reducing dementia risk. An active lifestyle during middle age reduces dementia risk but it remains to be determined if increased activity reduces dementia risk when MCI is already evident. Before this can be investigated conclusively, complex multimodal activity programmes are required that (1) combine multiple health promoting activities, (2) engage people with MCI, and (3) result in sufficient adherence rates.MethodsWe designed the ThinkingFit programme to engage people with MCI in a complex intervention comprised of three activity components: physical activity, group-based cognitive stimulation (GCST) and individual cognitive stimulation (ICST). Engagement and adherence was promoted by applying specific psychological techniques to enhance behavioural flexibility in an early pre-phase and during the course of the intervention. To pilot the intervention, participants served as their own controls during a 6- to 12-week run-in period, which was followed by 12 weeks of activity intervention.ResultsOut of 212 MCI patients screened, 163 were eligible, 70 consented and 67 completed the intervention (mean age 74 years). Activity adherence rates were high: physical activity = 71%; GCST = 83%; ICST = 67%. Significant treatment effects (p < .05) were evident on physical health outcomes (decreased BMI and systolic blood pressure, [pre/post values of 26.3/25.9 kg/m2 and 145/136 mmHg respectively]), fitness (decreased resting and recovery heart rate [68/65 bpm and 75/69 bpm]), and cognition (improved working memory [5.3/6.3 items]).ConclusionsWe found satisfactory recruitment, retention and engagement rates, coupled with significant treatment effects in elderly MCI patients. It appears feasible to conduct randomized controlled trials of the dementia prevention potential of complex multimodal activity programmes like ThinkingFit.Trial registrationClinicalTrials.gov registration nr: NCT01603862; date: 17/5/2012.