Pain processing in older adults with dementia-related cognitive impairment is associated with frontal neurodegeneration.

Experimental pain research has shown that pain processing seems to be heightened in dementia. It is unclear which neuropathological changes underlie these alterations. This study examined whether differences in pressure pain sensitivity and endogenous pain inhibition (conditioned pain modulation (CPM)) between individuals with a dementia-related cognitive impairment (N=23) and healthy controls (N=35) are linked to dementia-related neurodegeneration. Pain was assessed via self-report ratings and by analyzing the facial expression of pain using the Facial Action Coding System. We found that cognitively impaired individuals show decreased CPM inhibition as assessed by facial responses compared to healthy controls, which was mediated by decreased gray matter volume in the medial orbitofrontal and anterior cingulate cortex in the patient group. This study confirms previous findings of intensified pain processing in dementia when pain is assessed using non-verbal responses. Our findings suggest that a loss of pain inhibitory functioning caused by structural changes in prefrontal areas might be one of the underlying mechanisms responsible for amplified pain responses in individuals with a dementia-related cognitive impairment.

Pain Processing in Older Adults and Its Association with Prefrontal Characteristics.

Aging is known to affect nociceptive processing, e.g., the ability to inhibit pain. This study aims to investigate whether pain responses in older individuals are associated with prefrontal characteristics, namely (i) executive functioning performance and (ii) structural brain variations in the prefrontal cortex. Heat and pressure stimuli were applied to assess pressure pain sensitivity and endogenous pain inhibition in 46 healthy older individuals. Executive functioning performance was assessed in three domains (i.e., cognitive inhibition, shifting, and updating) and structural brain variations were assessed in both gray and white matter. Overall pain responses were significantly associated with the executive functioning domains cognitive inhibition and shifting. However, no specific type of pain response showed an especially strong association. Endogenous pain inhibition specifically showed a significant association with gray matter volume in the prefrontal cortex and with variations in white matter structure of tracts connecting the prefrontal cortex with the periaqueductal gray. Hierarchical regression analyses showed that these variations in the prefrontal cortex can explain variance in pain inhibition beyond what can be explained by executive functioning. This might indicate that known deficits in pain inhibition in older individuals are associated with structural variations in prefrontal areas.

Preservation of episodic memory in semantic dementia: The importance of regions beyond the medial temporal lobes.

Episodic memory impairment represents one of the hallmark clinical features of patients with Alzheimer's disease (AD) attributable to the degeneration of medial temporal and parietal regions of the brain. In contrast, a somewhat paradoxical profile of relatively intact episodic memory, particularly for non-verbal material, is observed in semantic dementia (SD), despite marked atrophy of the hippocampus. This retrospective study investigated the neural substrates of episodic memory retrieval in 20 patients with a diagnosis of SD and 21 disease-matched cases of AD and compared their performance to that of 35 age- and education-matched healthy older Controls. Participants completed the Rey Complex Figure and the memory subscale of the Addenbrooke's Cognitive Examination-Revised as indices of visual and verbal episodic recall, respectively. Relative to Controls, AD patients showed compromised memory performance on both visual and verbal memory tasks. In contrast, memory deficits in SD were modality-specific occurring exclusively on the verbal task. Controlling for semantic processing ameliorated these deficits in SD, while memory impairments persisted in AD. Voxel-based morphometry analyses revealed significant overlap in the neural correlates of verbal episodic memory in AD and SD with predominantly anteromedial regions, including the bilateral hippocampus, strongly implicated. Controlling for semantic processing negated this effect in SD, however, a distributed network of frontal, medial temporal, and parietal regions was implicated in AD. Our study corroborates the view that episodic memory deficits in SD arise very largely as a consequence of the conceptual loading of traditional tasks. We propose that the functional integrity of frontal and parietal regions enables new learning to occur in SD in the face of significant hippocampal and anteromedial temporal lobe pathology, underscoring the inherent complexity of the episodic memory circuitry.