The main objective of “Lifebrain” is to identify the determinants of brain, cognitive and mental (BCM) health at different stages of life. By integrating, harmonising and enriching major European neuroimaging studies across the life span, we will merge fine-grained BCM health measures of more than 5000 individuals. Longitudinal brain imaging, genetic and health data are available for a major part, as well as cognitive and mental health measures for the broader cohorts, exceeding 27,000 examinations in total. By linking these data to other databases and biobanks, including birth registries, national and regional archives, and by enriching them with a new online data collection and novel measures, we will address the risk factors and protective factors of BCM health. We will identify pathways through which risk and protective factors work and their moderators. Exploiting existing European infrastructures and initiatives, we hope to make major conceptual, methodological and analytical contributions towards large integrative cohorts and their efficient exploitation. We will thus provide novel information on BCM health maintenance, as well as the onset and course of BCM disorders. This will lay a foundation for earlier diagnosis of brain disorders, aberrant development and decline of BCM health, and translate into future preventive and therapeutic strategies. Aiming to improve clinical practice and public health we will work with stakeholders and health authorities, and thus provide the evidence base for prevention and intervention.

The contribution of education and intelligence to resilience against age-related cognitive decline is not clear, particularly in the presence of ‘normal for age’ minor brain abnormalities.

Participants (n = 208, mean age 69.2 years, s.d. = 5.4) in the Whitehall II imaging substudy attended for neuropsychological testing and multisequence 3T brain magnetic resonance imaging. Images were independently rated by three trained clinicians for global and hippocampal atrophy, periventricular and deep white matter changes.

Although none of the participants qualified for a clinical diagnosis of dementia, a screen for cognitive impairment (Montreal Cognitive Assessment (MoCA) <26) was abnormal in 22%. Hippocampal atrophy, in contrast to other brain measures, was associated with a reduced MoCA score even after controlling for age, gender, socioeconomic status, years of education and premorbid IQ. Premorbid IQ and socioeconomic status were associated with resilience in the presence of hippocampal atrophy.

Independent contributions from a priori risk (age, hippocampal atrophy) and resilience (premorbid function, socioeconomic status) combine to predict measured cognitive impairment.

Hypertension is associated with an increased risk of dementia and depression with uncertain longitudinal associations with brain structure.

To examine lifetime blood pressure as a predictor of brain structure in old age.

A total of 190 participants (mean age 69.3 years) from the Whitehall II study were screened for hypertension six times (1985–2013). In 2012–2013, participants had a 3T-magnetic resonance imaging (MRI) brain scan. Data from the MRI were analysed using automated and visual measures of global atrophy, hippocampal atrophy and white matter hyperintensities.

Longitudinally, higher mean arterial pressure predicted increased automated white matter hyperintensities (P<0.002). Cross-sectionally, hypertensive participants had increased automated white matter hyperintensities and visually rated deep white matter hyperintensities. There was no significant association with global or hippocampal atrophy.

Long-term exposure to high blood pressure predicts hyperintensities, particularly in deep white matter. The greatest changes are seen in those with severe forms of hypertension, suggesting a dose–response pattern.

An increasing number of studies have examined the effects of training of cognitive and other tasks on brain structure, using magnetic resonance imaging.

Studies combining cognitive and other tasks training with longitudinal imaging designs were reviewed, with a view to identify paradigms potentially applicable to treatment of cognitive impairment.

We identified 36 studies, employing training as variable as juggling, working memory, meditation, learning abstract information, and aerobic exercise. There were training-related structural changes, increases in gray matter volume, decreases, increases and decreases in different regions, or no change at all. There was increased integrity in white matter following training, but other patterns of results were also reported.

Questions still to be answered are: Are changes due to use-dependent effects or are they specific to learning? What are the underlying neural correlates of learning, the temporal dynamics of changes, the relations between structure and function, and the upper limits of improvement? How can gains be maintained? The question whether neuroplasticity will contribute to the treatment of dementia will need to be posed again at that stage.

Late-life depression is a common and heterogeneous illness, associated with structural abnormalities in both grey and white matter.

To examine the relationship between age at onset and magnetic resonance imaging (MRI) measures of grey and white matter to establish whether they support particular hypotheses regarding the anatomy and aetiology of network disruption in late-life depression.

We studied 36 participants with late-life depression. Grey matter was examined using T1-weighted MRI and analysed using voxel-based morphometry. The hippocampus was automatically segmented and volume and shape analysis performed. White matter was examined using diffusion tensor imaging and analysed using tract-based spatial statistics.

Later age at onset was significantly associated with reduced fractional anisotropy of widespread tracts, in particular the anterior thalamic radiation and superior longitudinal fasciculus. Earlier age at onset was associated with reduced hippocampal volume normalised to whole brain size bilaterally. However, no significant correlations were detected using hippocampal shape analysis or voxel-based morphometry.

Overall, the results were compatible with the vascular hypothesis, and provided some support for the glucocorticoid cascade hypothesis.

Cognitive impairment precedes the diagnosis of Alzheimer's disease. It is unclear which psychometric measures predict dementia, and what cut-off points should be used. Replicable cognitive measures to provide information about differential diagnosis and prognosis would be clinically useful.

In a prospective cohort study we investigated which measures distinguish between individuals with amnestic mild cognitive impairment (aMCI) that converts to dementia and those whose impairment does not, and which combination of measures best predicts the fate of people with aMCI.

Forty-four participants with aMCI underwent extensive neuropsychological assessment at baseline and annually thereafter for an average of 4 years. Differences in baseline cognitive performance of participants who were converters and non-converters to clinically diagnosed dementia were analysed. Classification accuracy was estimated by sensitivity, specificity, positive and negative predictive values and using logistic regression.

Forty-one percent of participants had progressed to dementia by the end of study, with a mean annual conversion rate of 11%. Most (63%) showed persisting or progressive cognitive impairment, irrespective of diagnosis. The Addenbrooke's Cognitive Examination together with the discrimination index of the Hopkins Verbal Learning Test – Revised (but none of the demographic indices) differentiated the participants who were converters from the non-converters at baseline with 74% accuracy.

Targeted neuropsychological assessment, beyond simple cognitive screening, could be used in clinical practice to provide individuals with aMCI with prognostic information and aid selective early initiation of monitoring and treatment among those who progress towards a clinically diagnosable dementia.

Magnetic seizure therapy, in which seizures are elicited with a high-frequency magnetic field, is under development as a new treatment for major depressive disorder. Its use may be justified if it produces the antidepressant effects of electroconvulsive therapy (ECT), coupled with limited cognitive side-effects.

To evaluate the usefulness of a new 100 Hz magnetic seizure therapy device.

We induced seizures with 100 Hz magnetic transcranial stimulation in 11 patients with major depressive disorder during one session of a regular course of ECT. Recovery times after seizures induced by magnetic seizure therapy and ECT were compared.

Seizures could be elicited in 10 of the 11 patients. Stimulation over the vertex produced tonic-clonic activity on 9 out of 11 occasions. Stimulation over the prefrontal midpoint elicited seizures on 3 out of 7 occasions. The mean duration of magnetically induced seizures was 31.3s, ranging from 10 to 86s. All patients had an exceptionally quick recovery of orientation: mean of 7 min 12s (s.d.=2 min 7 s, range 4 min 20s to 9 min 41 s). The recovery times were on average 15 min 35s shorter with magnetic seizure therapy than with ECT in the same patients (paired-samples t-test: P<0.0001). Patients reported feeling less confused after magnetic seizure therapy. Side-effects were confined to myoclonic movements, associated with the use of etomidate.

The new 100Hz magnetic stimulator elicits seizures in the majority of patients when administered over the vertex. Magnetic seizure therapy was associated with shorter recovery times and less confusion following treatment. Subsequent work will be required to assess the safety and effectiveness of magnetic seizure therapy in the treatment of depression.

There is current interest in exploring the different subtypes of mild cognitive impairment (MCI), in terms of both their epidemiology and their cognitive profile.

To examine the frequency of MCI subtypes presenting to a memory clinic and to document detailed neuropsychological profiles of patients with the amnestic subtype.

Consecutive tertiary referrals (n = 187) were psychiatrically evaluated; 45 patients met criteria for amnestic mild cognitive impairment (aMCI). A subgroup of 33 patients with aMCI as well as 21 healthy controls took part in a thorough neuropsychological examination.

Of the patients who were examined in greater neuropsychological detail, ten had pure aMCI (none with visual memory impairment only). Fifteen met criteria for non-amnestic MCI. Fifteen had normal neuropsychological profiles. Using more than one test increased sensitivity to detect episodic memory impairment.

Amnestic MCI is an important diagnosis in secondary and tertiary memory clinics. There is scope to improve the efficacy and sensitivity of the clinical assessment of this impairment.

The cognitive impairment of older depressed patients with late- as opposed to early-onset illness may show important differences, in that patients with early onset may suffer predominantly from impaired episodic memory, and those with late onset mainly from reductions of executive function and processing speed.

We searched Medline and EMBASE as well as individual papers' reference lists for relevant publications, recording comparisons in neuropsychological test results between early-onset depression (EOD), late-onset depression (LOD) and healthy volunteers. Effect sizes are presented for cognitive domains, such as executive function, processing speed, episodic memory, semantic memory and mental state examination.

Patients with LOD showed greater reductions in processing speed and executive function than patients with EOD and controls. Both patient groups showed reduced function in all domains, except mental state, compared with controls.

Pronounced executive deficits are typical of the late-onset patients described in published studies, while episodic memory impairment is not specific to early-onset illness. Possible reasons and confounders are discussed.