Quantitative multi-modal MRI of the Hippocampus and cognitive ability in community-dwelling older subjects

Abstract

Hippocampal structural integrity is commonly quantified using volumetric measurements derived from brain magnetic resonance imaging (MRI). Previously reported associations with cognitive decline have not been consistent. We investigate hippocampal integrity using quantitative MRI techniques and its association with cognitive abilities in older age.Participants from the Lothian Birth Cohort 1936 underwent brain MRI at mean age 73 years. Longitudinal relaxation time (T1), magnetization transfer ratio (MTR), fractional anisotropy (FA) and mean diffusivity (MD) were measured in the hippocampus. General factors of fluid-type intelligence (g), cognitive processing speed (speed) and memory were obtained at age 73 years, as well as childhood IQ test results at age 11 years. Amongst 565 older adults, multivariate linear regression showed that, after correcting for ICV, gender and age 11 IQ, larger left hippocampal volume was significantly associated with better memory ability (β = .11, p = .003), but not with speed or g. Using quantitative MRI and after correcting for multiple testing, higher T1 and MD were significantly associated with lower scores of g (β range = −.11 to −.14, p < .001), speed (β range = −.15 to −.20, p < .001) and memory (β range = −.10 to −.12, p < .001). Higher MTR and FA in the hippocampus were also significantly associated with higher scores of g (β range = .17 to .18, p < .0001) and speed (β range = .10 to .15, p < .0001), but not memory.Quantitative multi-modal MRI assessments were more sensitive at detecting cognition-hippocampal integrity associations than volumetric measurements, resulting in stronger associations between MRI biomarkers and age-related cognition changes.

Associations between hippocampal morphology, diffusion characteristics, and salivary cortisol in older men

“…This interpretation may be partly corroborated by the findings for the hippocampus reported herein, which are in the same direction for the same cortisol measure and appear to be driven by the same measure of microstructure (MD). As stated at the outset, despite preliminary evidence that hippocampal diffusion measures may be relevant for brain and cognitive ageing (Madsen et al, 2012, Aribisala et al, 2014, Weston et al, 2015), the microstructural properties that might influence water diffusion in the hippocampus have yet to be clearly elucidated and susceptibility to partial volume effects such as CSF contamination cannot be ruled out, such that these diffusion analyses should be treated with caution.…”

“…Several lines of evidence indicate that hippocampal diffusion may provide a more sensitive biomarker for age-related neurodegenerative disease (reviewed in Weston et al, 2015). In the same overall sample that we examine here, these measures reportedly exhibit stronger cross-sectional associations with cognitive ability in older age than hippocampal volume (Aribisala et al, 2014), suggesting that individual differences in hippocampal microstructure may be an informative biomarker in brain ageing research. Hippocampal mean diffusivity has been identified as potentially sensitive to cortisol levels, though in a smaller group with a wider age range (n = 58, Madsen et al, 2012) in which older participants were not well represented (<10 participants aged over 60 years).…”

Visit-to-Visit Blood Pressure Variability in Young Adulthood and Hippocampal Volume and Integrity at Middle Age

“…21,27 The clinical relevance of hippocampal FA as a measure of hippocampal integrity has been reported. 28,29 …”

Hippocampal morphology and cognitive functions in community-dwelling older people: the Lothian Birth Cohort 1936

“…First approximations of left and right hippocampal segmentations were obtained from an automated pipeline that uses tools from the FMRIB Software Library version 4.1 (Oxford, UK; http://www.fmrib.ox.ac.uk/fsl/), and an age-relevant template (Farrell et al., 2009), followed by visual inspection and manual correction when required using Analyze 10.0 software (Mayo Clinic, Rochester, MN, USA; www.analyzedirect.com), and saved as binary masks as per previous publications (Aribisala et al., 2014, Wardlaw et al., 2011). Semi-automated measurements of intracranial volume (ICV; contents within the inner skull table including brain tissue, cerebrospinal fluid, veins, and dura; Valdes Hernandez et al., 2012) were used for normalization.…”

“…Lower hippocampal volumes among patients with Alzheimer's disease (AD) mild cognitive impairment (MCI), and depression are associated with poorer verbal and non-verbal/spatial memory scores (Bonner-Jackson et al., 2015, Grundman et al., 2003, Hickie et al., 2005, Peruzza Marchiani et al., 2008; see van Petten, 2004 for a review pre-2004). Similarly, among nonpathological samples of older adults, differences in hippocampal volume are related to poorer memory performance, mainly quantified using verbal recall tasks (Aribisala et al., 2014, den Heijer et al., 2012, Raz and Rodrigue, 2006, Ystad et al., 2009). Reduction in hippocampal volume has also been linked with poorer cognitive performance in a variety of cognitive domains in addition to memory, such as fluid intelligence (Reuben et al., 2011) and processing speed (Papp et al., 2014).…”