Subcortical brain structures and the risk of dementia in the Rotterdam Study

Abstract

Introduction: Volumetric and morphological changes in subcortical brain structures are present in persons with dementia, but it is unknown if these changes occur prior to diagnosis. Methods: Between 2005 and 2016, 5522 Rotterdam Study participants (mean age: 64.4) underwent cerebral magnetic resonance imaging (MRI) and were followed for development of dementia until 2018. Volume and shape measures were obtained for seven subcortical structures. Results: During 12 years of follow-up, 272 dementia cases occurred. Mean volumes of thalamus (hazard ratio [HR] per standard deviation [SD] decrease 1.94, 95% confidence interval [CI]: 1.55-2.43), amygdala (HR 1.66,, and hippocampus (HR 1.64, 95% CI: 1.43-1.88) were strongly associated with dementia risk. Associations for accumbens, pallidum, and caudate volumes were less pronounced. Shape analyses identified regional surface changes in the amygdala, limbic thalamus, and caudate.Discussion: Structure of the amygdala, thalamus, hippocampus, and caudate is associated with risk of dementia in a large population-based cohort of older adults.

Antidepressant use in relation to dementia risk, cognitive decline, and brain atrophy

“…Next, we applied linear regression models to estimate baseline differences in brain volume between users and non‐users. The association of antidepressant use with change in brain volume over time of the total brain, white matter, gray matter, and subcortical structures involved in memory and mood regulation (i.e., hippocampus, amygdala, and thalamus 38 ) were estimated using linear mixed models, adding total intracranial volume to the aforementioned set of covariates. Analyses were again repeated separately for antidepressant type.…”

Intracranial arteriosclerosis and the risk of dementia: A population‐based cohort study

“…An automated quality metric was obtained for each scan that was used to identify images of low quality. In addition, 200 randomly selected scans were visually rated for quality assessment 7 . Location‐specific information on measures of cSVD and cortical brain volumes was not readily available.…”

“…As both arteriosclerosis and dementia develop over the course of years, there is a need for longitudinal investigations covering extensive time intervals. Second, previous investigations have focused primarily on the anterior cerebral circulation, whereas the posterior circulation represents the basis of the vascularization of subcortical brain structures such as the thalamus and hippocampus, which are important in dementia etiology 6‐8 . Posterior cerebral arteriosclerosis is thought, at least in part, to be a separate entity from anterior arteriosclerosis, given that both have distinct cardiovascular risk profiles and markedly different prevalence rates 9 .…”

“…Fourth, intracranial arteriosclerosis is a risk factor for stroke and cerebral small vessel disease (cSVD), which in turn represent important risk factors for dementia 18‐20 . Moreover, because the amygdala is vascularized predominantly by the anterior cerebral circulation and the thalamus and hippocampus by the posterior brain circulation, including subcortical brain structures might provide important insights into the location‐specific effects of intracranial arteriosclerosis on dementia 6,7 . Hence, stroke, cSVD, and subcortical structures might act as mediators on the pathway from arteriosclerosis to dementia, but it remains undetermined what share of dementia risk is mediated through these processes.…”

“…Second, previous investigations have focused primarily on the anterior cerebral circulation, whereas the posterior circulation represents the basis of the vascularization of subcortical brain structures such as the thalamus and hippocampus, which are important in dementia etiology. 6 , 7 , 8 Posterior cerebral arteriosclerosis is thought, at least in part, to be a separate entity from anterior arteriosclerosis, given that both have distinct cardiovascular risk profiles and markedly different prevalence rates. 9 Moreover, arteriosclerosis of the posterior cerebral circulation is related to white matter pathology, 10 and white matter pathology in dementia occurs more frequently in brain areas supplied by the posterior cerebral circulation (i.e., parieto‐occipital and posterior periventricular areas).…”