Asymmetric thinning of the cerebral cortex across the adult lifespan is accelerated in Alzheimer’s disease

Abstract

Aging and Alzheimer’s disease (AD) are associated with progressive brain disorganization. Although structural asymmetry is an organizing feature of the cerebral cortex it is unknown whether continuous age- and AD-related cortical degradation alters cortical asymmetry. Here, in multiple longitudinal adult lifespan cohorts we show that higher-order cortical regions exhibiting pronounced asymmetry at age ~20 also show progressive asymmetry-loss across the adult lifespan. Hence, accelerated thinning of the (previously) thicker homotopic hemisphere is a feature of aging. This organizational principle showed high consistency across cohorts in the Lifebrain consortium, and both the topological patterns and temporal dynamics of asymmetry-loss were markedly similar across replicating samples. Asymmetry-change was further accelerated in AD. Results suggest a system-wide dedifferentiation of the adaptive asymmetric organization of heteromodal cortex in aging and AD.

The genetic architecture of structural left–right asymmetry of the human brain

“…As we found that brain asymmetry-related genes tend to be especially highly expressed in the embryonic brain, it seems likely that the genetic overlap of brain asymmetry and disorders reflects a genetic susceptibility to alterations of early neurodevelopment away from the typical trajectory. However, brain asymmetry continues to develop throughout the lifespan 107 , 108 , and the UK Biobank consists of middle- to older-age adults, so that our mvGWAS may have also identified genetic factors that affect brain asymmetrical changes later in life.…”

The enigma and implications of brain hemispheric asymmetry in neurodegenerative diseases

“… 45–47 Leftward asymmetry in cortical thickness and in the putamen also varies with age, which also may be relevant for neurodegenerative diseases that typically occur later in life. 42 , 48 …”

“… 112 Interestingly, the apparent vulnerability of the left hemisphere in Alzheimer’s disease may in part be an accelerated form of normal ageing; cortical thinning is known to occur asymmetrically with age, resulting in a gradual loss of normal asymmetry, and this occurs more rapidly in Alzheimer’s disease. 48 The prominent neuropathological features identified in Alzheimer’s disease are intracellular neurofibrillary tangles of phosphorylated tau protein and extracellular amyloid-beta (Aβ) plaques associated with neuronal dysfunction and death; these may also contribute to the phenotypic asymmetries seen in Alzheimer’s disease. PET scans as well as post-mortem studies of hemispheric distributions of these proteins in Alzheimer’s disease reveal asymmetric patterns of Aβ pathology in some cases.…”

Differential Ageing of the Brain Hemispheres: Evidence from a Longitudinal Study of Hand Preferences in Common Marmosets

“…In fact, in marmosets there is no correspondence between eye preference and hand preference [61], meaning that each is a manifestation of a different laterality and may show different changes with age. Consistent with this, a recent longitudinal study of cortical thickness in humans from 20 to 80-plus years of age has found region-specific thinning in different areas of cortex in the left and right hemispheres [62], with an overall pattern of consistently decreasing asymmetry across the adult life-span [62].…”