Alzheimer's dementia is merely the final stage of a pathological process that spans decades. Before clinicians can detect dementia, AD pathology may have already reached the insular cortex, which is related to autonomic control of heart rate and blood pressure. Insular lesions, particularly on the right, are associated with bradyarrhythmias, decreased heart rate variability (HRV), and increased mortality. Thus, preclinical AD should be considered as a possible explanation for """"""""cardiovascular"""""""" I fall-related morbidity and mortality in non-demented elderly persons. Autopsy studies suggest that 40% of octogenarians may be at risk for this level of AD pathology. 20-40% of healthy octogenarians have unexplained """"""""age related"""""""" supaventricular arrhythmias on 24-hour Holter records. Mortality in AD is specifically associated with right hemisphere metabolism and tests of constructional praxis. This effect is not limited to clinical AD. Survival is decreased in cases with """"""""Mild Cognitive Impairment"""""""" (MCI) as well. We have recently observed increased mortality in non-demented, non-disabled, independent living octogenarians with mild constructional impairments. Mortality was also associated with signs of pre-emergent AD (like anosmia). This suggests that AD has significant effects on mortality at a preclinical stage in the disease process. This study will examine the association between right hemisphere dysfunction and autonomic control at three levels of cognitive impairment [e.g. frank AD, Mild Cognitive Impairment (MCI) (i.e. preclinical AD), and normal controls]. All subjects will be free of significant cardiac disease (CAD). Right hemisphere function will be assessed by measures of constructional praxis, and regional cerebral blood flow by Functional Magnetic Resonance Imaging (fMRI). Autonomic control will be assessed by statistical analyses of HRV derived from 24 Holter records, supplemented by the frequency and severity of selected cardiac arrhythmias, orthostatic blood pressures, and symptom self-reports. A significant effect of right hemisphere function on autonomic control in non-demented persons at risk for AD would have important implications. The community prevalence of MCI has been estimated to be 38% of community dwelling elderly. Constructional tasks could help identify those at risk. Minorities may be disproportionately vulnerable. Some dementia treatments are known to reduce HRV, and possibly mortality as well. Alternatively, some psychotropics may increase arrhythmia-related mortality, possibly via a central mechanism.
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| Royall, Donald R (2008) Insular Alzheimer disease pathology and the psychometric correlates of mortality. Cleve Clin J Med 75 Suppl 2:S97-9 |
| Royall, Donald R; Palmer, Raymond F; Chiodo, Laura K et al. (2008) Clock-drawing potentially mediates the effect of depression on mortality: replication in three cohorts. Int J Geriatr Psychiatry 23:821-9 |
| Royall, Donald R; Gao, Jia-Hong; Kellogg Jr, Dean L (2006) Insular Alzheimer's disease pathology as a cause of ""age-related"" autonomic dysfunction and mortality in the non-demented elderly. Med Hypotheses 67:747-58 |
