Abstract
In contrast to the idea that hippocampal and amygdala volume loss occur in late phases of neurodegeneration, recent contributions point to the relevance of preexisting structural deficits that are associated with aging and are independent of amyloid deposition in preclinical Alzheimer disease cases. The present work explores GM hippocampal and amygdala volumes in elderly controls displaying the first signs of cognitive decline. 455 subjects (263 females), including 374 controls (228 females) and 81 middle cognitive impairment subjects (35 females), underwent two neuropsychological evaluations (baseline and 18 months follow-up) and a MRI-T1 examination (only baseline). Clinical assessment included Mini-Mental State Examination (MMSE), Clinical Dementia Rating scale, Hospitalized Anxiety and Depression scale, the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery and RI-48 Cued Recall Test (RI-48) for episodic memory. Based on their cognitive performance, we defined the controls as stable controls (sCON) and deteriorating controls (dCONs). Analyses included volumetric assessment, shape analyses and linear regressions between GM volume loss and differences in clinical scores between baseline and follow-up. Significant GM volume decrease in hippocampus bilaterally and right amygdala was found in dCON compared to sCON (p < 0.05). Lower right amygdala volumes were measured in mild cognitive impairment (MCI) compared to sCON (p < 0.05). Shape analyses revealed that atrophy was more pronounced at the superior- posterior lateral side of the hippocampus and amygdala. Significant correlations were found between GM volume of left hippocampus and the delta of MMSE and RI-48 scores in dCON and MCI groups separately. Decreased hippocampal and right amygdala volumes precede the first signs of cognitive decline in healthy elderly controls at the pre-MCI state. Left hippocampus volume may also predict short-term changes of overall cognition in these vulnerable cases.
Highlights
The first neuropathological hallmarks described by Alois Alzheimer more than a century ago, amyloid deposits and neurofibrillary tangles (NFTs), are present in hippocampal subdivisions and restricted neocortical areas of cognitively normal people and their densities increase with age (Giannakopoulos et al, 2007)
The deteriorating controls (dCONs) cases were slightly older than mild cognitive impairment (MCI) cases (p < 0.05) with no age differences between stable controls (sCON) and the other two diagnostic groups [F(2,452) = 4.34, η2 = 0.2, p < 0.05]
Upon follow-up, higher Mini-Mental State Examination (MMSE) scores were found in sCON compared to dCON (p < 0.001) and MCI (p < 0.001) and in dCON group compared to MCI cases (p < 0.01) [F(2,452) = 26.54, η2 = 0.11, p < 0.001]
Summary
The first neuropathological hallmarks described by Alois Alzheimer more than a century ago, amyloid deposits and neurofibrillary tangles (NFTs), are present in hippocampal subdivisions and restricted neocortical areas of cognitively normal people and their densities increase with age (Giannakopoulos et al, 2007). Subsequent advent of modern non-invasive diagnostic techniques enabled early detection of diverse AD-related pathological events in vivo, and prepared the ground for the notion of preclinical AD (Lazarczyk et al, 2012) This concept refers to asymptomatic stages of AD that are characterized by the progressive development of functional and subsequently structural changes in cortical areas in the absence of clinically overt signs of the disease. Appearance of various biological changes suggestive of AD pathology in controls has been extensively documented They may precede clinically overt dementia by many years, or even decades (Reiman et al, 2004; Shaw et al, 2007; Lazarczyk et al, 2012), defining a temporally wide preclinical phase of the disease (Lazarczyk et al, 2012). We explored the patterns of GM loss in hippocampus and amygdala in these elderly controls displaying the first signs of cognitive decline as compared to stable controls as well as MCI cases as a second group of comparison
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