VALUTAZIONE DELLA FUNZIONE AUTONOMICA NEL MILD COGNITIVE IMPAIRMENT TRAMITE ANALISI SPETTRALE DELLA HEART RATE VARIABILITY

Background The analysis of Heart Rate Variability (HRV), available in most commercial Holter devices, provides a simple method for the assessment of autonomic function. The potential association between Mild Cognitive Impairment (MCI) and autonomic dysfunction, indirectly supported by data in the literature and replete with clinical implications, has been investigated by a single study which, however, failed to highlight it. Aim To evaluate autonomic function in subjects with MCI by means of spectral analysis of HRV applied to a standardized experimental protocol which includes two provocative tests. Materials and Methods We evaluated 40 subjects with MCI and 40 subjects with normal cognitive function (control group), recruited among those consecutively undergoing neuropsychological testing at the Geriatric Medicine Unit of the Policlinico in Milan between January 2011 and December 2012. Spectral analysis of HRV was carried out on 5-minute electrocardiographic recordings belonging to the three stages of the protocol: baseline (supine rest with free breathing), active orthostasis (orthosympathetic stimulation) and paced breathing at 12 breaths/min (parasympathetic stimulation). We mainly focused on those autonomic indices that better express the reciprocal interaction between the two branches of the autonomic nervous system: normalized Low Frequency Power (LFn), normalized High Frequency Power (HFn) and the LF/HF ratio (R). These indices were considered as such in each of the three stages of the protocol but also in their changes from baseline to the active part of each protocol (∆LFn, ∆HFn, ∆R) which represent the response to the manoeuvre and are more sensitive measures of autonomic modulation. We also recorded blood pressure after one, three, five and ten minutes of standing Student's t-test was employed to compare autonomic indices and blood pressures between the two groups and the analysis of covariance (ANCOVA) was used, when appropriate, to control for the effect of potential confounders. Results Significant differences between the two groups were not found in baseline conditions, but only during the provocative tests and in the responses to the tests. In MCI subjects, compared to controls, there was a shift of sympathovagal balance towards parasympathetic modulation during active orthostasis (LFn 52.7±20.0 vs 65.8±17.0, p=0.010; HFn 26.2 ±14.3 vs 18.5±10.3, p=0.007; R 3.4±3.3 vs 5.2±3.8, p=0.030) and towards orthosympathetic modulation during paced breathing (LFn 49.1±19.3 vs 38.1±18.2, p= 0.012; HFn 38.2±17.7 vs 47.8±18.7, p=0.024).Foremost, in MCI, subjects, relative to controls, there was a significant blunting of the physiological response to active orthostasis in all its components (∆LFn 3.6±25.7 vs17.1±16.8, p=0.019; ∆HFn -1.4±13.4 vs -12.5±14.2, p=0.008; ∆R 0.7±3.0 vs 2.8±2.6, p=0.010) and there was a borderline significant attenuation of the physiological response to paced breathing only in the component pertaining to orthosympathetic inhibition (∆LFn -0.7±24.0 vs -10.8±20.9, p=0.053).Moreover, in MCI subjects, compared to controls, the systolic blood pressures after three and ten minutes of standing were lower (129.0±16.7 vs 137.7±18.9, p=0.034; 124.4±16.0 vs 135.2±21.4, p=0.033 respectively). Conclusions MCI subjects show an autonomic dysfunction which is not evident in baseline conditions but is revealed by provocative tests that challenge the autonomic nervous system. More specifically,the responses to the provocative tests seem to outline an autonomic pattern characterized by total orthosympathetic dysfunction and partial parasympathetic dysfunction, potentially linked to an involvement of the right insula. The reduction in the orthostatic systolic blood pressures is a possible consequence of the autonomic dysfunction and, although modest, could hold clinical significance in elderly subjects in whom cerebral autoregulation is impaired. Longitudinal studies will be required to better define the clinical relevance of the autonomic dysfunction in terms of mortality and progression to dementia.