Author name cluster

Klaus P. Ebmeier

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16 papers

1 author row

YNICL Journal 2022 Journal Article

Alcohol consumption and MRI markers of brain structure and function: Cohort study of 25,378 UK Biobank participants

Anya Topiwala
Klaus P. Ebmeier
Thomas Maullin-Sapey
Thomas E. Nichols

Moderate alcohol consumption is widespread but its impact on brain structure and function is contentious. The relationship between alcohol intake and structural and functional neuroimaging indices, the threshold intake for associations, and whether population subgroups are at higher risk of alcohol-related brain harm remain unclear. 25,378 UK Biobank participants (mean age 54.9 ± 7.4 years, 12,254 female) underwent multi-modal MRI 9.6 ± 1.1 years after study baseline. Alcohol use was self-reported at baseline (2006-10). T1-weighted, diffusion weighted and resting state images were examined. Lower total grey matter volumes were observed in those drinking as little as 7-14 units (56-112 g) weekly. Higher alcohol consumption was associated with multiple markers of white matter microstructure, including lower fractional anisotropy, higher mean and radial diffusivity in a spatially distributed pattern across the brain. Associations between functional connectivity and alcohol intake were observed in the default mode, central executive, attention, salience and visual resting state networks. Relationships between total grey matter and alcohol were stronger than other modifiable factors, including blood pressure and smoking, and robust to unobserved confounding. Frequent binging, higher blood pressure and BMI steepened the negative association between alcohol and total grey matter volume. In this large observational cohort study, alcohol consumption was associated with multiple structural and functional MRI markers in mid- to late-life.

YNICL Journal 2022 Journal Article

Associations between abdominal adipose tissue, reproductive span, and brain characteristics in post-menopausal women

Louise S. Schindler
Sivaniya Subramaniapillai
Claudia Barth
Dennis van der Meer
Mads L. Pedersen
Tobias Kaufmann
Ivan I. Maximov
Jennifer Linge

The menopause transition involves changes in oestrogens and adipose tissue distribution, which may influence female brain health post-menopause. Although increased central fat accumulation is linked to risk of cardiometabolic diseases, adipose tissue also serves as the primary biosynthesis site of oestrogens post-menopause. It is unclear whether different types of adipose tissue play diverging roles in female brain health post-menopause, and whether this depends on lifetime oestrogen exposure, which can have lasting effects on the brain and body even after menopause. Using the UK Biobank sample, we investigated associations between brain characteristics and visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT) in 10,251 post-menopausal females, and assessed whether the relationships varied depending on length of reproductive span (age at menarche to age at menopause). To parse the effects of common genetic variation, we computed polygenic scores for reproductive span. The results showed that higher VAT and ASAT were both associated with higher grey and white matter brain age, and greater white matter hyperintensity load. The associations varied positively with reproductive span, indicating more prominent associations between adipose tissue and brain measures in females with a longer reproductive span. The effects were in general small, but could not be fully explained by genetic variation or relevant confounders. Our findings indicate that associations between abdominal adipose tissue and brain health post-menopause may partly depend on individual differences in cumulative oestrogen exposure during reproductive years, emphasising the complexity of neural and endocrine ageing processes in females.

YNICL Journal 2022 Journal Article

Associations of depression and regional brain structure across the adult lifespan: Pooled analyses of six population-based and two clinical cohort studies in the European Lifebrain consortium

Julia Binnewies
Laura Nawijn
Andreas M. Brandmaier
William F.C. Baaré
David Bartrés-Faz
Christian A. Drevon
Sandra Düzel
Anders M. Fjell

OBJECTIVE: Major depressive disorder has been associated with lower prefrontal thickness and hippocampal volume, but it is unknown whether this association also holds for depressive symptoms in the general population. We investigated associations of depressive symptoms and depression status with brain structures across population-based and patient-control cohorts, and explored whether these associations are similar over the lifespan and across sexes. METHODS: We included 3,447 participants aged 18-89 years from six population-based and two clinical patient-control cohorts of the European Lifebrain consortium. Cross-sectional meta-analyses using individual person data were performed for associations of depressive symptoms and depression status with FreeSurfer-derived thickness of bilateral rostral anterior cingulate cortex (rACC) and medial orbitofrontal cortex (mOFC), and hippocampal and total grey matter volume (GMV), separately for population-based and clinical cohorts. RESULTS: = -0.25). Effect sizes were slightly larger for presence of moderate-to-severe depression. Associations were similar across age groups and sex. Across population-based cohorts, no associations between depression and brain structures were observed. CONCLUSIONS: Fitting with previous meta-analyses, depressive symptoms and depression status were associated with lower mOFC, rACC thickness, and hippocampal and total grey matter volume in clinical patient-control cohorts, although effect sizes were small. The absence of consistent associations in population-based cohorts with mostly mild depressive symptoms, suggests that significantly lower thickness and volume of the studied brain structures are only detectable in clinical populations with more severe depressive symptoms.

YNICL Journal 2022 Journal Article

Hippocampal maintenance after a 12-month physical activity intervention in older adults: The REACT MRI study

Naiara Demnitz
Afroditi Stathi
Janet Withall
Candida Stainer
Poppy Seager
Jolanthe De Koning
Patrick Esser
Thomas Wassenaar

BACKGROUND: Physical activity interventions have had varying results on modifying hippocampal volume. METHODS: The Retirement in Action (REACT) study conducted a randomised-controlled trial of a 12-month physical activity and behaviour maintenance intervention in older adults at risk of mobility impairments. The physical activity sessions were delivered twice weekly for the first twelve weeks, and then reduced to once weekly, to groups of 15 participants. Activities included cardiovascular, strength, balance and flexibility exercises. A sub-sample of participants in the physical activity (N = 54) and control arms (N = 48) underwent a 3 T MRI brain scan and cognitive assessments at baseline, 6- and 12-months (mean age = 76.6 years, 6.8 SD). It was hypothesised that the intervention would lead to a reduced rate of decline in hippocampal volume. Group differences in changes in cognition were also examined. RESULTS: As hypothesised, we found a maintenance in left hippocampal volume in the intervention arm, in comparison with the control arm after 12 months (p = 0.027). In a secondary analysis, this effect was attenuated after including age, sex and education level as covariates (p = 0.057). There was no significant between-group difference in the right hippocampus (p = 0.405). Contrary to our hypothesis, we did not find a beneficial effect of the intervention on cognitive outcomes. CONCLUSIONS: Our findings suggest that a community-based physical activity intervention can significantly ward-off hippocampal atrophy in older adults. While the lack of effects on cognition may limit the interpretability of our results, our findings of hippocampal maintenance are promising given the potential clinical relevance of protecting the hippocampus from age-related decline.

YNIMG Journal 2022 Journal Article

Inter- and intra-individual variation in brain structural-cognition relationships in aging

Raihaan Patel
Clare E. Mackay
Michelle G. Jansen
Gabriel A. Devenyi
M. Clare O'Donoghue
Mika Kivimäki
Archana Singh-Manoux
Enikő Zsoldos

The sources of inter- and intra-individual variability in age-related cognitive decline remain poorly understood. We examined the association between 20-year trajectories of cognitive decline and multimodal brain structure and morphology in older age. We used the Whitehall II Study, an extensively characterised cohort with 3T brain magnetic resonance images acquired at older age (mean age = 69.52 ± 4.9) and 5 repeated cognitive performance assessments between mid-life (mean age = 53.2 ±4.9 years) and late-life (mean age = 67.7 ± 4.9). Using non-negative matrix factorization, we identified 10 brain components integrating cortical thickness, surface area, fractional anisotropy, and mean and radial diffusivities. We observed two latent variables describing distinct brain-cognition associations. The first describes variations in 5 structural components associated with low mid-life performance across multiple cognitive domains, decline in reasoning, but maintenance of fluency abilities. The second describes variations in 6 structural components associated with low mid-life performance in fluency and memory, but retention of multiple abilities. Expression of latent variables predicts future cognition 3.2 years later (mean age = 70.87 ± 4.9). This data-driven approach highlights brain-cognition relationships wherein individuals degrees of cognitive decline and maintenance across diverse cognitive functions are both positively and negatively associated with markers of cortical structure.

YNICL Journal 2021 Journal Article

White matter hyperintensities classified according to intensity and spatial location reveal specific associations with cognitive performance

Luca Melazzini
Clare E. Mackay
Valentina Bordin
Sana Suri
Enikő Zsoldos
Nicola Filippini
Abda Mahmood
Vaanathi Sundaresan

White matter hyperintensities (WMHs) on T2-weighted images are radiological signs of cerebral small vessel disease. As their total volume is variably associated with cognition, a new approach that integrates multiple radiological criteria is warranted. Location may matter, as periventricular WMHs have been shown to be associated with cognitive impairments. WMHs that appear as hypointense in T1-weighted images (T1w) may also indicate the most severe component of WMHs. We developed an automatic method that sub-classifies WMHs into four categories (periventricular/deep and T1w-hypointense/nonT1w-hypointense) using MRI data from 684 community-dwelling older adults from the Whitehall II study. To test if location and intensity information can impact cognition, we derived two general linear models using either overall or subdivided volumes. Results showed that periventricular T1w-hypointense WMHs were significantly associated with poorer performance in the trail making A (p = 0. 011), digit symbol (p = 0. 028) and digit coding (p = 0. 009) tests. We found no association between total WMH volume and cognition. These findings suggest that sub-classifying WMHs according to both location and intensity in T1w reveals specific associations with cognitive performance.

YNIMG Journal 2020 Journal Article

Multimodal brain-age prediction and cardiovascular risk: The Whitehall II MRI sub-study

Ann-Marie G. de Lange
Melis Anatürk
Sana Suri
Tobias Kaufmann
James H. Cole
Ludovica Griffanti
Enikő Zsoldos
Daria E.A. Jensen

Brain age is becoming a widely applied imaging-based biomarker of neural aging and potential proxy for brain integrity and health. We estimated multimodal and modality-specific brain age in the Whitehall II (WHII) MRI cohort using machine learning and imaging-derived measures of gray matter (GM) morphology, white matter microstructure (WM), and resting state functional connectivity (FC). The results showed that the prediction accuracy improved when multiple imaging modalities were included in the model (R2 = 0. 30, 95% CI [0. 24, 0. 36]). The modality-specific GM and WM models showed similar performance (R2 = 0. 22 [0. 16, 0. 27] and R2 = 0. 24 [0. 18, 0. 30], respectively), while the FC model showed the lowest prediction accuracy (R2 = 0. 002 [-0. 005, 0. 008]), indicating that the FC features were less related to chronological age compared to structural measures. Follow-up analyses showed that FC predictions were similarly low in a matched sub-sample from UK Biobank, and although FC predictions were consistently lower than GM predictions, the accuracy improved with increasing sample size and age range. Cardiovascular risk factors, including high blood pressure, alcohol intake, and stroke risk score, were each associated with brain aging in the WHII cohort. Blood pressure showed a stronger association with white matter compared to gray matter, while no differences in the associations of alcohol intake and stroke risk with these modalities were observed. In conclusion, machine-learning based brain age prediction can reduce the dimensionality of neuroimaging data to provide meaningful biomarkers of individual brain aging. However, model performance depends on study-specific characteristics including sample size and age range, which may cause discrepancies in findings across studies.

YNIMG Journal 2018 Journal Article

Classification and characterization of periventricular and deep white matter hyperintensities on MRI: A study in older adults

Ludovica Griffanti
Mark Jenkinson
Sana Suri
Enikő Zsoldos
Abda Mahmood
Nicola Filippini
Claire E Sexton
Anya Topiwala

White matter hyperintensities (WMH) are frequently divided into periventricular (PWMH) and deep (DWMH), and the two classes have been associated with different cognitive, microstructural, and clinical correlates. However, although this distinction is widely used in visual ratings scales, how to best anatomically define the two classes is still disputed. In fact, the methods used to define PWMH and DWMH vary significantly between studies, making results difficult to compare. The purpose of this study was twofold: first, to compare four current criteria used to define PWMH and DWMH in a cohort of healthy older adults (mean age: 69. 58 ± 5. 33 years) by quantifying possible differences in terms of estimated volumes; second, to explore associations between the two WMH sub-classes with cognition, tissue microstructure and cardiovascular risk factors, analysing the impact of different criteria on the specific associations. Our results suggest that the classification criterion used for the definition of PWMH and DWMH should not be considered a major obstacle for the comparison of different studies. We observed that higher PWMH load is associated with reduced cognitive function, higher mean arterial pressure and age. Higher DWMH load is associated with higher body mass index. PWMH have lower fractional anisotropy than DWMH, which also have more heterogeneous microstructure. These findings support the hypothesis that PWMH and DWMH are different entities and that their distinction can provide useful information about healthy and pathological aging processes.

YNIMG Journal 2017 Journal Article

Distinct resting-state functional connections associated with episodic and visuospatial memory in older adults

Sana Suri
Anya Topiwala
Nicola Filippini
Enikő Zsoldos
Abda Mahmood
Claire E. Sexton
Archana Singh-Manoux
Mika Kivimäki

Episodic and spatial memory are commonly impaired in ageing and Alzheimer's disease. Volumetric and task-based functional magnetic resonance imaging (fMRI) studies suggest a preferential involvement of the medial temporal lobe (MTL), particularly the hippocampus, in episodic and spatial memory processing. The present study examined how these two memory types were related in terms of their associated resting-state functional architecture. 3T multiband resting state fMRI scans from 497 participants (60–82 years old) of the cross-sectional Whitehall II Imaging sub-study were analysed using an unbiased, data-driven network-modelling technique (FSLNets). Factor analysis was performed on the cognitive battery; the Hopkins Verbal Learning test and Rey-Osterreith Complex Figure test factors were used to assess verbal and visuospatial memory respectively. We present a map of the macroscopic functional connectome for the Whitehall II Imaging sub-study, comprising 58 functionally distinct nodes clustered into five major resting-state networks. Within this map we identified distinct functional connections associated with verbal and visuospatial memory. Functional anticorrelation between the hippocampal formation and the frontal pole was significantly associated with better verbal memory in an age-dependent manner. In contrast, hippocampus–motor and parietal–motor functional connections were associated with visuospatial memory independently of age. These relationships were not driven by grey matter volume and were unique to the respective memory domain. Our findings provide new insights into current models of brain-behaviour interactions, and suggest that while both episodic and visuospatial memory engage MTL nodes of the default mode network, the two memory domains differ in terms of the associated functional connections between the MTL and other resting-state brain networks.

YNIMG Journal 2017 Journal Article

Effect of age and the APOE gene on metabolite concentrations in the posterior cingulate cortex

Sana Suri
Uzay Emir
Charlotte J. Stagg
Jamie Near
Ralf Mekle
Florian Schubert
Enikő Zsoldos
Abda Mahmood

Proton magnetic resonance spectroscopy (1H-MRS) has provided valuable information about the neurochemical profile of Alzheimer's disease (AD). However, its clinical utility has been limited in part by the lack of consistent information on how metabolite concentrations vary in the normal aging brain and in carriers of apolipoprotein E (APOE) ε4, an established risk gene for AD. We quantified metabolites within an 8cm3 voxel within the posterior cingulate cortex (PCC)/precuneus in 30 younger (20–40 years) and 151 cognitively healthy older individuals (60–85 years). All 1H-MRS scans were performed at 3T using the short-echo SPECIAL sequence and analyzed with LCModel. The effect of APOE was assessed in a sub-set of 130 volunteers. Older participants had significantly higher myo-inositol and creatine, and significantly lower glutathione and glutamate than younger participants. There was no significant effect of APOE or an interaction between APOE and age on the metabolite profile. Our data suggest that creatine, a commonly used reference metabolite in 1H-MRS studies, does not remain stable across adulthood within this region and therefore may not be a suitable reference in studies involving a broad age-range. Increases in creatine and myo-inositol may reflect age-related glial proliferation; decreases in glutamate and glutathione suggest a decline in synaptic and antioxidant efficiency. Our findings inform longitudinal clinical studies by characterizing age-related metabolite changes in a non-clinical sample.

YNIMG Journal 2016 Journal Article

A systematic review of MRI studies examining the relationship between physical fitness and activity and the white matter of the ageing brain

Claire E. Sexton
Jill F. Betts
Naiara Demnitz
Helen Dawes
Klaus P. Ebmeier
Heidi Johansen-Berg

Higher levels of physical fitness or activity (PFA) have been shown to have beneficial effects on cognitive function and grey matter volumes in older adults. However, the relationship between PFA and the brain's white matter (WM) is not yet well established. Here, we aim to provide a comprehensive and systematic review of magnetic resonance imaging studies examining the effects of PFA on the WM of the ageing brain. Twenty-nine studies were included in the review: eleven examined WM volume, fourteen WM lesions, and nine WM microstructure. While many studies found that higher levels of PFA were associated with greater WM volumes, reduced volume or severity of WM lesions, or improved measures of WM microstructure, a number of negative findings have also been published. Meta-analyses of global measures of WM volume and WM lesion volume yielded significant, but small, effect sizes. Overall, we found evidence for cautious support of links between PFA and WM structure, and highlighted key areas for future research including the extent to which the relationship between PFA and WM structure is anatomically specific, the influence of possible confounding factors, and the relationship between PFA, WM and cognition.

YNIMG Journal 2014 Journal Article

Apolipoprotein E genotype, gender and age modulate connectivity of the hippocampus in healthy adults

Verena Heise
Nicola Filippini
Aaron J. Trachtenberg
Sana Suri
Klaus P. Ebmeier
Clare E. Mackay

Important risk factors for Alzheimer's disease (AD) are ageing and the Apolipoprotein E (APOE) ε4 allele, with female APOE ε4 carriers having the greatest risk. In this study we investigated effects of AD risk factors on connectivity of the hippocampus, a structure that shows early AD related pathology. Resting-state functional magnetic resonance imaging and diffusion tensor imaging data from 86 cognitively healthy subjects aged 30 to 78years were analysed. Female APOE ε4 carriers showed overall significantly reduced functional connectivity between the hippocampus and precuneus/posterior cingulate cortex (PCC) and a significant age-related decrease in connectivity of these regions. In females and APOE ε4 carriers we found significantly reduced white matter integrity of the tract connecting the hippocampus and PCC with a significant positive correlation of white matter integrity and resting-state connectivity. Increased vulnerability of the connection between the hippocampus and PCC might be one reason for increased AD risk in female APOE ε4 carriers. Interventions targeting hippocampal connectivity might be especially effective in this at risk population.

YNIMG Journal 2014 Journal Article

ICA-based artefact removal and accelerated fMRI acquisition for improved resting state network imaging

Ludovica Griffanti
Gholamreza Salimi-Khorshidi
Christian F. Beckmann
Edward J. Auerbach
Gwenaëlle Douaud
Claire E. Sexton
Enikő Zsoldos
Klaus P. Ebmeier

The identification of resting state networks (RSNs) and the quantification of their functional connectivity in resting-state fMRI (rfMRI) are seriously hindered by the presence of artefacts, many of which overlap spatially or spectrally with RSNs. Moreover, recent developments in fMRI acquisition yield data with higher spatial and temporal resolutions, but may increase artefacts both spatially and/or temporally. Hence the correct identification and removal of non-neural fluctuations is crucial, especially in accelerated acquisitions. In this paper we investigate the effectiveness of three data-driven cleaning procedures, compare standard against higher (spatial and temporal) resolution accelerated fMRI acquisitions, and investigate the combined effect of different acquisitions and different cleanup approaches. We applied single-subject independent component analysis (ICA), followed by automatic component classification with FMRIB's ICA-based X-noiseifier (FIX) to identify artefactual components. We then compared two first-level (within-subject) cleaning approaches for removing those artefacts and motion-related fluctuations from the data. The effectiveness of the cleaning procedures was assessed using time series (amplitude and spectra), network matrix and spatial map analyses. For time series and network analyses we also tested the effect of a second-level cleaning (informed by group-level analysis). Comparing these approaches, the preferable balance between noise removal and signal loss was achieved by regressing out of the data the full space of motion-related fluctuations and only the unique variance of the artefactual ICA components. Using similar analyses, we also investigated the effects of different cleaning approaches on data from different acquisition sequences. With the optimal cleaning procedures, functional connectivity results from accelerated data were statistically comparable or significantly better than the standard (unaccelerated) acquisition, and, crucially, with higher spatial and temporal resolution. Moreover, we were able to perform higher dimensionality ICA decompositions with the accelerated data, which is very valuable for detailed network analyses.

YNIMG Journal 2012 Journal Article

The effects of APOE on the functional architecture of the resting brain

Aaron J. Trachtenberg
Nicola Filippini
Klaus P. Ebmeier
Steve M. Smith
Fredrik Karpe
Clare E. Mackay

There is a well-established association between APOE genotype and the risk of developing Alzheimer's disease (AD). Relative to individuals with the common ε3/ε3 genotype, carriers of the ε4 allele are at increased risk of developing AD, while carriers of the ε2 allele appear to be protected against the disease. However, we recently reported that in a sample of cognitively healthy adults, both ε4 and ε2 carriers showed nearly identical changes in the pattern of fMRI activity during memory and non-memory tasks, relative to ε3 homozygotes. These findings suggest that the effects of APOE on brain function are not tightly linked to the effects of this gene on AD risk. Here we test the hypothesis that APOE has an intrinsic effect on the brain's functional networks. Resting-state fMRI was used to compare the pattern of functional connectivity of a variety of resting-state networks between 77 cognitively healthy participants aged 32 to 55 with different APOE genotypes (23 ε2/ε3, 20 ε3/ε3, 26 ε3/ε4, and 8 ε4/ε4). Differences between genotype groups were found in two hippocampal networks, the auditory network, the left frontal–parietal network, and the lateral visual network. While there was considerable variety in the brain regions affected and the direction of change across networks, the main finding was that changes in functional connectivity were similar in ε4 and ε2 carriers, relative to ε3 homozygotes. APOE appears to have an intrinsic effect on the differentiation of functional networks in the brain. This effect is apparent in cognitively healthy adults and does not manifest in a manner reflective of the link between APOE and AD risk. Rather, the effects of APOE on brain function may relate to the role of this gene in neurodevelopment.

YNIMG Journal 2002 Journal Article

Statistical Parametric Mapping of 99mTc-HMPAO-SPECT Images for the Diagnosis of Alzheimer's Disease: Normalizing to Cerebellar Tracer Uptake

Darius Soonawala
Tania Amin
Klaus P. Ebmeier
J.Douglas Steele
Nadine J. Dougall
Jonathan Best
Octave Migneco
Flavio Nobili

Background: For a quantitative comparison of images obtained during 99mTc-hexamethylpropylene amine oxime (HMPAO) single-photon emission computed tomography (SPECT), brain activity values are usually normalized to a reference region. In studies of Alzheimer-type dementia (ATD), the cerebellum is often used as a reference region, assuming that it is spared any major pathological involvement. Statistical parametric mapping (SPM) may enhance the evaluation of SPECT scans in ATD patients. However, current SPM software only allows scaling to average whole brain activity (i. e. , global normalization). The aim of this study was to develop an easily applied, objective, and reproducible method for determining average cerebellar tracer uptake so that images can be scaled specifically to cerebellar activity prior to the performance of SPM analysis. We also investigated whether cerebellar normalization increases the sensitivity and specificity of SPM analysis of ATD patients compared with global normalization. Methods: Image files were taken from a parallel study investigating the use of SPECT as a diagnostic tool for early onset of ATD. Two methods for determining cerebellar activity were developed: one manually, using templates, the other automated, using specified coordinates entered into a Matlab routine. Group comparison of ATD patients versus controls (= healthy volunteers and depressed patients) was performed on a voxel-by-voxel basis using SPM 96 on Windows 95. Receiver operator characteristics (ROC) were computed for 20 student raters examining patient and control scans with and without single-subject SPMs. Results: The reduction of cerebral blood flow in the group of ATD patients appeared 1. 7 times greater in spatial extent when the tracer uptake was normalized to cerebellum rather than to average whole brain activity. Computing the reverse contrast (reductions in the control group compared with ATD patients) produced clusters of significance in globally normalized images which were not manifest after normalizing to cerebellum. This is consistent with the notion that the cerebellum is spared in ATD. Analysis of the area under the ROC curve showed that cerebellar-normalized SPM produced significantly improved accuracy over perfusion scans alone. Conclusion: An easily applied, objective, reproducible method was developed for normalizing images to cerebellum prior to the performance of SPM analysis. Cerebellar normalization produced more extensive abnormalities in SPM analyses of ATD patients than global normalization. Furthermore, cerebellar normalization produced marginally more accurate diagnostic results in single-scan SPM analysis of ATD patients than did global normalization.

YNIMG Journal 1998 Journal Article

A Voxel-Based Analysis of Cerebral Perfusion in Dementia and Depression of Old Age

Klaus P. Ebmeier
Michael F. Glabus
Neil Prentice
Ann Ryman
Guy M. Goodwin

Thirty-nine elderly depressed patients as well as 15 demented patients with Alzheimer's disease and 11 healthy volunteers were imaged at rest with a high resolution single-slice 12-detector head scanner (SME-Neuro 900) and the cerebral perfusion marker99mTc-Exametazime (HM-PAO). Statistical parametric maps were computed to compare early- and late-onset depressed, Alzheimer patients and healthy volunteers and to examine associations between regional perfusion and clinical and MRI variables. Patients with late-onset depression showed reductions in temporal lobe perfusion compared with early-onset depression and controls. Alzheimer patients had the expected reduced perfusion in temporoparietal and prefontal cortex, as well as basal ganglia, compared with healthy controls. Compared with depressed patients, they showed a relative reduction in temporoparietal cortex, only. This difference was more pronounced between Alzheimer patients and early onset, compared to late-onset patients with depression. Periventricular white matter changes on MRI were associated with temporal lobe reductions of tracer uptake in depression. In the Alzheimer group, deep white matter MRI changes were associated with frontal perfusion deficits. Our results support a vulnerability hypothesis, which predicts that patients with late-onset depression will show more brain changes than patients with an early onset of their illness. Statistical parametric mapping in patients with organic psychiatric brain syndromes is feasible and promising as a clinical and research method.