Aikaterini Xekardaki

Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder.

BACKGROUND Previous magnetic resonance imaging (MRI) studies in young patients with bipolar disorder indicated the presence of grey matter concentration changes as well as microstructural alterations in white matter in various neocortical areas and the corpus callosum. Whether these structural changes are also present in elderly patients with bipolar disorder with long-lasting clinical evolution remains unclear. METHODS We performed a prospective MRI study of consecutive elderly, euthymic patients with bipolar disorder and healthy, elderly controls. We conducted a voxel-based morphometry (VBM) analysis and a tract-based spatial statistics (TBSS) analysis to assess fractional anisotropy and longitudinal, radial and mean diffusivity derived by diffusion tensor imaging (DTI). RESULTS We included 19 patients with bipolar disorder and 47 controls in our study. Fractional anisotropy was the most sensitive DTI marker and decreased significantly in the ventral part of the corpus callosum in patients with bipolar disorder. Longitudinal, radial and mean diffusivity showed no significant between-group differences. Grey matter concentration was reduced in patients with bipolar disorder in the right anterior insula, head of the caudate nucleus, nucleus accumbens, ventral putamen and frontal orbital cortex. Conversely, there was no grey matter concentration or fractional anisotropy increase in any brain region in patients with bipolar disorder compared with controls. LIMITATIONS The major limitation of our study is the small number of patients with bipolar disorder. CONCLUSION Our data document the concomitant presence of grey matter concentration decreases in the anterior limbic areas and the reduced fibre tract coherence in the corpus callosum of elderly patients with long-lasting bipolar disorder.

Longitudinal analysis of cognitive performances and structural brain changes in late-life bipolar disorder.

Cross‐sectional studies in bipolar disorder (BD) suggested the presence of cognitive deficits and subtle magnetic resonance imaging (MRI) changes in limbic areas that may persist at euthymic stages. Whether or not cognitive and MRI changes represent stable attributes of BD or evolve with time is still matter of debate. To address this issue, we performed a 2‐year longitudinal study including detailed neuropsychological and magnetic resonance imaging (MRI) analyses of 15 euthymic older BD patients and 15 controls.

Arterial Spin Labeling May Contribute to the Prediction of Cognitive Deterioration in Healthy Elderly Individuals

PURPOSE To explore whether arterial spin labeling (ASL) imaging in cognitively intact elderly individuals may be used to predict subsequent early neuropsychological decline. MATERIALS AND METHODS The local ethics committee approved this prospective study, and written informed consent was obtained from all participants. A total of 148 consecutive control subjects were included, 75 of whom had stable cognitive function (sCON) (mean age, 75.9 years ± 3.4 [standard deviation]; 43 female) and 73 of whom had deteriorated cognitive function (dCON) at 18-month clinical follow-up (mean age, 76.8 years ± 4.1; 44 female). An additional 65 patients with mild cognitive impairment (MCI) (mean age, 76.2 years ± 6.1; 25 female) were also included. Two-dimensional pulsed ASL was performed at the baseline visit. Statistical analysis included whole-brain voxelwise analysis of the ASL relative cerebral blood flow (CBF) data, receiver operating characteristic (ROC) curve analysis of the posterior cingulate cortex (PCC), and voxel-based morphometry analysis of gray matter. RESULTS The voxelwise comparison of ASL revealed decreased relative CBF in the dCON group compared with that in the sCON group and slightly more pronounced relative CBF in the MCI group compared with that in the sCON group, most notably in the PCC (P < .05 corrected). Comparison of the dCON group with the MCI group revealed no significant differences. ROC analysis of relative CBF in the PCC enabled discrimination of dCON (P < .001; area under the ROC curve, 0.66). There was no confounding focal gray matter atrophy. CONCLUSION Reduced ASL in the PCC at baseline is associated with the development of subsequent subtle neuropsychological deficits in healthy elderly control subjects. At a group level, ASL patterns in subjects with dCON are similar to those in patients with MCI at baseline, indicating that these subjects may initially maintain their cognitive status via mobilization of their neurocognitive reserve at baseline; however, they are likely to develop subsequent subtle cognitive deficits.

Neuroimaging of dementia in 2013: what radiologists need to know

AbstractThe structural and functional neuroimaging of dementia have substantially evolved over the last few years. The most common forms of dementia, Alzheimer disease (AD), Lewy body dementia (LBD) and fronto-temporal lobar degeneration (FTLD), have distinct patterns of cortical atrophy and hypometabolism that evolve over time, as reviewed in the first part of this article. The second part discusses unspecific white matter alterations on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images as well as cerebral microbleeds, which often occur during normal aging and may affect cognition. The third part summarises molecular neuroimaging biomarkers recently developed to visualise amyloid deposits, tau protein deposits and neurotransmitter systems. The fourth section reviews the utility of advanced image analysis techniques as predictive biomarkers of cognitive decline in individuals with early symptoms compatible with mild cognitive impairment (MCI). As only about half of MCI cases will progress to clinically overt dementia, whereas the other half remain stable or might even improve, the discrimination of stable versus progressive MCI is of paramount importance for both individual patient treatment and patient selection for clinical trials. The fifth and final part discusses the inter-individual variation in the neurocognitive reserve, which is a potential constraint for all proposed methods. Key Points• Many forms of dementia have spatial atrophy patterns detectable on neuroimaging.• Early treatment of dementia is beneficial, indicating the need for early diagnosis.• Advanced image analysis techniques detect subtle anomalies invisible on radiological evaluation.• Inter-individual variation explains variable cognitive impairment despite the same degree of atrophy.

Neuropathological changes in aging brain

Neuropathological hallmarks of Alzheimers disease (AD) include tangles (NFT) and beta amyloid (Aβ) plaques. Despite numerous neuropathological studies that assessed the relationship of cognitive decline with neuropathologic lesions, their correlation still remains unclear. NFTs and Aβ plaques have been widely implicated and described in normal aging. The number of NFTs in the CA1 and the entorhinal cortex seems to be more closely related to cognitive status, compared to the amyloid load whose role still remains controversial in the AD. In this review, we refer to our main studies performed in Geneva during the past two decades attempting to assess the correlation of pathology with clinical expression. The theory of cognitive reserve has been proposed for further understanding of interindividual differences in terms of compensation despite the presence of pathological lesions. The increasing prevalence of the AD, the limitations of actual treatments, as well as the high public cost reflect the imperative need for better therapeutic and early diagnosis strategies in the future.

Microvascular Burden and Alzheimer-Type Lesions Across the Age Spectrum

The occurrence of microvascular and small macrovascular lesions and Alzheimers disease (AD)-related pathology in the aging human brain is a well-described phenomenon. Although there is a wide consensus about the relationship between macroscopic vascular lesions and incident dementia, the cognitive consequences of the progressive accumulation of these small vascular lesions in the human brain are still a matter of debate. Among the vast group of small vessel-related forms of ischemic brain injuries, the present review discusses the cognitive impact of cortical microinfarcts, subcortical gray matter and deep white matter lacunes, periventricular and diffuse white matter demyelinations, and focal or diffuse gliosis in old age. A special focus will be on the sub-types of microvascular lesions not detected by currently available neuroimaging studies in routine clinical settings. After providing a critical overview of in vivo data on white matter demyelinations and lacunes, we summarize the clinicopathological studies performed by our center in large cohorts of individuals with microvascular lesions and concomitant AD-related pathology across two age ranges (the younger old, 65-85 years old, versus the oldest old, nonagenarians and centenarians). In conjunction with other autopsy datasets, these observations fully support the idea that cortical microinfarcts are the only consistent determinant of cognitive decline across the entire spectrum from pure vascular cases to cases with combined vascular and AD lesion burden.

Microvascular pathology in late-life depression

Since the era of Gaupp who introduced the concept of atheroscletic depressive disorder, the concept of late-life depression has been correlated with cerebrovascular comorbidities, microvascular lesions, frontal cortical and subcortical gray and white matter hyperintensities. The predominant neuropsychological deficits concern the domains of planning, organization and abstraction, with executive dysfunction being the predominant finding. MRI studies reveal a higher prevalence of white matter lesions in elderly patients with depression. Molecular mechanisms underlying the disease still remain unclear. Hyperhomocysteinemia has been associated with depression through its toxicity to neurons and blood vessels. Endothelial dysfunction is another possible mechanism referring to the loss of vasodilatation capacity. Inflammatory phenomena, such as increased peripheral leucocytes, elevated CRP and cytokine levels, could play a role in endothelial dysfunction. In this review we will briefly combine findings from neurobiological, epidemiological, structural and post-mortem data. A more complex model in late-life depression combining different modalities could be an elucidating approach to the diseases etiopathogeny in the future.

Individual Severity of AD-Type Lesions, Aß Oligomers, and Comorbidity in the Brain Aging

In cognitively intact individuals and patients with Alzheimer’s disease (AD) the formation of neurofibrillary tangles (NFTs), senile plaques (SPs), and the synaptic loss characterizes the neuropathology of brain aging. There is a differential cortical vulnerability to the degenerative process in extreme brain aging. In the oldest-old population the distribution and the severity of NFTs and SPs could be different compared to younger persons.

Decrease in Amyloid Deposition in Aging Brain—An Autopsy Study

During the last century a worldwide population aging was observed, thanks to improved living and medical conditions. It is not known whether these progresses have had any effect on cerebral aging.

Neuropathology of Parkinsonism in Alzheimer’s Disease

About 30 % of Alzheimer’s disease (AD) patients develop parkinsonian features, but Lewy body pathology is not always present at autopsy. So the neuropathological substrate of extrapyramidal signs in AD remains unclear. In the present study neuronal and neurofibrillary tangle (NFT) densities were counted in the substantia nigra pars compacta (SN) and in the putamen of 22 AD patients, 11 with and 11 without parkinsonism. Parkinsonism was defined as the presence of bradykinesia and at least one of resting tremor, rigidity, or gait disorders. Our results showed that parkinsonism in AD is related to a significant neuronal loss both in the SN and in the putamen, suggesting pre- and postsynaptic alterations of the nigrostriatal pathway.