Thomas Dannhauser

An fMRI study of verbal episodic memory encoding in amnestic mild cognitive impairment

Amnestic mild cognitive impairment (aMCI) is a high-risk and often prodromal state for the development of Alzheimers disease (AD) and is characterised by isolated episodic memory impairment. Functional neuroimaging studies in healthy subjects consistently report left prefrontal cortex (PFC) activation during verbal episodic memory encoding. The PFC activation at encoding is related to semantic processing which enhances memory. The purpose of this study was to ascertain whether impaired verbal episodic memory in aMCI is related to PFC dysfunction. Using functional magnetic resonance imaging (fMRI) we compared 10 aMCI patients with 10 elderly controls during verbal encoding. The encoding task was sensitive to the effects of semantic processing. Subsequent recognition was tested to measure encoding success. Behavioural results revealed impaired recognition and a lower false recognition rate for semantically related distracters (lures) in aMCI, which suggest impaired semantic processing at encoding. Both groups activated left hemispheric PFC, insula, premotor cortex and cerebellum, but group comparisons revealed decreased activation in left ventrolateral PFC in the aMCI group. The magnitude of activation in left ventrolateral PFC during encoding was positively correlated with recognition accuracy in the control group but not in the aMCI group. We propose that verbal episodic memory impairment in aMCI is related to PFC dysfunction which affects semantic processing at encoding.

Subjective cognitive impairment: increased prefrontal cortex activation compared to controls during an encoding task

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.

Subjective cognitive impairment: Functional MRI during a divided attention task

BACKGROUND Individuals with subjective cognitive impairment (SCI) have persistent memory complaints but normal neurocognitive performance. For some, this may represent a pre-mild cognitive impairment (MCI) stage of Alzheimers disease (AD). Given that attentional deficits and associated brain activation changes are present early in the course of AD, we aimed to determine whether SCI is associated with brain activation changes during attentional processing. METHODS Eleven SCI subjects and 10 controls completed a divided attention task during functional magnetic resonance imaging. RESULTS SCI and control groups did not differ in sociodemographic, neurocognitive or behavioural measures. When group activation during the divided attention task was compared, the SCI group demonstrated increased activation in left medial temporal lobe, bilateral thalamus, posterior cingulate and caudate. CONCLUSION 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.

Aging effects on functional auditory and visual processing using fMRI with variable sensory loading

INTRODUCTION Traditionally, studies investigating the functional implications of age-related structural brain alterations have focused on higher cognitive processes; by increasing stimulus load, these studies assess behavioral and neurophysiological performance. In order to understand age-related changes in these higher cognitive processes, it is crucial to examine changes in visual and auditory processes that are the gateways to higher cognitive functions. This study provides evidence for age-related functional decline in visual and auditory processing, and regional alterations in functional brain processing, using non-invasive neuroimaging. METHODS Using functional magnetic resonance imaging (fMRI), younger (n=11; mean age=31) and older (n=10; mean age=68) adults were imaged while observing flashing checkerboard images (passive visual stimuli) and hearing word lists (passive auditory stimuli) across varying stimuli presentation rates. RESULTS Younger adults showed greater overall levels of temporal and occipital cortical activation than older adults for both auditory and visual stimuli. The relative change in activity as a function of stimulus presentation rate showed differences between young and older participants. In visual cortex, the older group showed a decrease in fMRI blood oxygen level dependent (BOLD) signal magnitude as stimulus frequency increased, whereas the younger group showed a linear increase. In auditory cortex, the younger group showed a relative increase as a function of word presentation rate, while older participants showed a relatively stable magnitude of fMRI BOLD response across all rates. When analyzing participants across all ages, only the auditory cortical activation showed a continuous, monotonically decreasing BOLD signal magnitude as a function of age. CONCLUSIONS Our preliminary findings show an age-related decline in demand-related, passive early sensory processing. As stimulus demand increases, visual and auditory cortex do not show increases in activity in older compared to younger people. This may negatively impact on the fidelity of information available to higher cognitive processing. Such evidence may inform future studies focused on cognitive decline in aging.

Memory complaints with and without memory impairment: the impact of leukoaraiosis on cognition.

White matter alterations, leukoaraiosis (LA) on structural MRI, are associated with cognitive deficits and increased risk of dementia. LA may also impact on subjective memory complaints in otherwise healthy older adults. Little is known about the interplay between LA memory complaints and cognition. We investigated cognitive phenotypes associated with LA in 42 non-demented older adults categorized as having subjective cognitive complaints with no objective cognitive impairment-the subjective cognitive impairment group (SCI; n = 12), amnesic mild cognitive impairment (aMCI; n = 20), or healthy controls (HC; n = 11). We measured LA severity on MRI with a 40-point visual rating scale. Controlling for age and Mini-Mental State Examination (MMSE) score, analyses revealed multiple between-group differences. Follow-up linear regression models investigating the underlying contributors to each clinic groups cognitive profile indicated that LA contributed to learning slope variance (after accounting for age and MMSE) but only for the SCI group. Although the SCI group showed a significantly steeper learning slope when compared to HC and aMCI, increasing LA severity negatively impacted this groups rate of learning. This, in conjunction with the significant contribution of age on SCI learning slope performance variance suggests that greater LA burden at a younger age may contribute to subtle changes in learning for individuals with subjective cognitive complaints.

A systematic review of reviews to identify key research opportunities within the field of eHealth implementation

Introduction This paper is a systematic review of the relevant literature surrounding the implementation and utilisation of eHealth to identify key challenges and opportunities to future eHealth applications. Methods NHS Evidence, PubMed, IEEE Explorer, Cochrane Library and JMIR Publications were all searched for reviews published between 1 January 2010 and 30 June 2017. Results A total of 47 papers met the final inclusion criterion. The published literature focused on a wide array of challenges categorised into five areas, facing the implementation and utilisation of eHealth; from this, four areas of opportunity to advance eHealth were identified. Discussion The five challenge areas are (C1) stakeholders and system users, (C2) technology and interoperability, (C3) cost-effectiveness and start-up costs, (C4) legal clarity and legal framework and (C5) local context and regional differences. The four opportunity areas are (O1) participation and contribution, (O2) foundation and sustainability, (O3) improvement and productivity and (O4) identification and application. Conclusion The literature analysed in this systematic review identifies design and implementation priorities that can guide the development and utilisation of future eHealth initiatives.

The neural correlates of verbal episodic memory encoding in prodromal probable Alzheimer's disease at the stage of amnestic mild cognitive impairment: An fMRI study

tissue volumes were assessed with linear regression, adjusted for relevant confounders. Results: Higher CT-assessed calcification load in all vessel beds was associated with worse cognitive scores in all domains. Adjustment for total brain volume attenuated these associations, except for the associations between extracranial and intracranial carotid artery calcifications and motor speed in men. A higher load of extracranial carotid artery calcifications in men and intracranial carotid artery calcifications in women was significantly associated with smaller total brain volume and smaller white matter volume. In women, aortic calcifications were strongly associated with smaller grey matter volume. Calcifications in any vessel bed were not associated with hippocampal volume. Adjustment for cardiovascular risk factors or carotid plaque did not change these associations. Conclusions: A higher arterial calcification load is associated with worse cognitive function. Furthermore, calcification load in specific vessel beds is associated with smaller total brain volume, white matter volume and grey matter volume. The association between arterial calcification load and cognitive function is partly mediated by its effect on brain tissue volumes.

S25-05 Subjective cognitive impairment: Functional MRI during divided attention and measurement of amyloid load using 11C-PIB PET

Background Evidence suggests that healthy older adults with subjective memory complaints are at increased risk of dementia. Subjective Cognitive Impairment (SCI) may precede Mild Cognitive Impairment (MCI) in the clinical continuum of Alzheimers disease (AD). Attentional deficits may be present early in AD, and associated functional changes have been reported in both MCI and AD. In the present study, activation during divided attention in SCI subjects was investigated using functional magnetic resonance imaging (fMRI). Additionally, amyloid uptake was investigated using 11 C-PIB with positron emission tomography (PET). Methods Brain activation in 11 SCI subjects and 10 controls was compared during a divided attention task using fMRI. Additionally, five SCI subjects and 14 cognitively normal healthy controls underwent 11 C-PIB PET scanning. Criteria for diagnosis of SCI were: 1. self-reported memory complaints, 2. objectively normal cognition on detailed neurocognitive testing, 3. absence of psychiatric or causative physical illness, 4. normal activities of daily living and 5. absence of MCI or dementia. Results There were no differences in performance between SCI and control groups in terms of cognitive or behavioural measures. However, SCIs had increased activation in left medial temporal lobe, and bilateral thalamus, posterior cingulate and caudate. One SCI subject and one control subject had a pattern of 11 C-PIB uptake similar to that seen in AD. Conclusions The activation changes identified in SCI may relate to compensatory increased activation in the face of early AD pathology. Larger, longitudinal studies are needed to determine the extent and significance of PIB uptake in SCI.

Passive processing of visual and auditory stimuli in the young and elderly: a neuroimaging study

There is surprisingly little literature on age-related effectsin passive visual and auditory processing in humans. Inthis study, we use parameterised visual and auditory stim-uli to investigate the relationship between a) visual fre-quency and graded visual cortical activations b) auditoryword presentation frequency and graded auditory corticalactivations in both young and elderly groups. Weattempted to model the relationship between visual /auditory stimuli frequency and differential effects on cor-tical activation in both groups.