Finding of increased caudate nucleus in patients with Alzheimer's disease
We recently performed a study to evaluate the clinical usefulness of an automated MRI assessment method called NeuroQuant® (NQ) in distinguishing Alzheimer's disease dementia (AD) from non‐dementia (subjective or mild cognitive impairment) or from other dementia disorders.4 A secondary finding of this study was that the volume of the caudate nucleus, as a ratio of total intracranial volume, was found to be larger in patients with AD compared to patients without dementia. We found this interesting and wanted to explore the results in greater depth with the aim of identifying factors that are associated with the NQ measurement of the caudate nucleus.
The caudate nucleus is part of the striatum of the basal ganglia. Because of extensive afferent and efferent connections and cortico‐striato‐thalamic loops, the area is important for both cognition and motor function. Tangle and plaque pathology, the typical characteristics of Alzheimer's disease, have been found in several brain regions including the caudate nucleus, and studies have found atrophy of the caudate nucleus and other parts of the basal ganglia in the preclinical and clinical stages of AD.5
The caudate nucleus and hippocampus have demonstrated different roles in learning and memory processes; the caudate nucleus is involved in procedural learning,8 the formation of habits,9 and stimulus‐response learning10 which involves learning to produce a specific action in response to a stimulus such as a landmark. The hippocampus, on the other hand, is involved in explicit memory functions including episodic memory and allocentric spatial learning and memory, that is, learning and memory of the relationships between landmarks in the environment.11 Research has suggested that these different memory systems can function independently and can be competitive.12 Based on these findings, one can hypothesize that, during the progression of AD with increasing atrophy of the hippocampus, the caudate nucleus could potentially receive increasing stimulation, leading to a negative relationship between the volumes of the caudate nucleus and the hippocampus. Furthermore, Bohbot et al.14 studied 599 healthy participants between 8 and 80 years of age and found decreasing hippocampus‐dependent spatial learning strategies in favor of caudate nucleus‐dependent response learning strategies across the lifespan. So, an increase in caudate nucleus activity seems to even occur throughout the healthy lifespan.
We have found only one study reporting an increase of caudate nucleus volume in Alzheimer's disease. This was found to precede later atrophy in non‐symptomatic presenilin‐1 mutation carriers.15 In normal aging, the caudate nucleus volume has generally been found to decrease with age,16 but results from different studies are inconsistent.17 Walhovd et al.16described a U‐shaped trajectory of the volume of the caudate nucleus with age, such that more atrophy of the caudate nucleus is found in midlife and less atrophy in the later years of life. In addition, in total, less prominent age‐related atrophy was reported for the caudate nucleus as compared to other brain structures. Different segmenting methods have been suggested as a possible reason for the conflicting results,16 as the caudate nucleus has been found to be challenging to segment accurately.