Autonomic function predicts cognitive decline in mild cognitive impairment: Evidence from power spectral analysis of heart rate variability in a longitudinal study

Paola Nicolini; Tiziano Lucchi; Carlo Abbate; Silvia Inglese; Emanuele Tomasini; Daniela Mari; Paolo D Rossi; Marco Vicenzi

doi:10.3389/fnagi.2022.886023

Autonomic function predicts cognitive decline in mild cognitive impairment: Evidence from power spectral analysis of heart rate variability in a longitudinal study

Front Aging Neurosci. 2022 Sep 15:14:886023. doi: 10.3389/fnagi.2022.886023. eCollection 2022.

Authors

Paola Nicolini¹, Tiziano Lucchi¹, Carlo Abbate^{1

2}, Silvia Inglese¹, Emanuele Tomasini^{1

2}, Daniela Mari³, Paolo D Rossi¹, Marco Vicenzi^{4

5}

Affiliations

¹ Geriatric Unit, Internal Medicine Department, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
² IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy.
³ Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
⁴ Dyspnea Lab, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
⁵ Cardiovascular Disease Unit, Internal Medicine Department, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Abstract

Background: Despite the emerging clinical relevance of heart rate variability (HRV) as a potential biomarker of cognitive decline and as a candidate target for intervention, there is a dearth of research on the prospective relationship between HRV and cognitive change. In particular, no study has addressed this issue in subjects with a diagnosis of cognitive status including cognitive impairment.

Objective: To investigate HRV as a predictor of cognitive decline in subjects with normal cognition (NC) or Mild Cognitive Impairment (MCI). Specifically, we tested the literature-based hypothesis that the HRV response to different physical challenges would predict decline in different cognitive domains.

Methods: This longitudinal study represents the approximately 3-year follow-up of a previous cross-sectional study enrolling 80 older outpatients (aged ≥ 65). At baseline, power spectral analysis of HRV was performed on five-minute electrocardiographic recordings at rest and during a sympathetic (active standing) and a parasympathetic (paced breathing) challenge. We focused on normalized HRV measures [normalized low frequency power (LFn) and the low frequency to high frequency power ratio (LF/HF)] and on their dynamic response from rest to challenge (Δ HRV). Extensive neuropsychological testing was used to diagnose cognitive status at baseline and to evaluate cognitive change over the follow-up via annualized changes in cognitive Z-scores. The association between Δ HRV and cognitive change was explored by means of linear regression, unadjusted and adjusted for potential confounders.

Results: In subjects diagnosed with MCI at baseline a greater response to a sympathetic challenge predicted a greater decline in episodic memory [adjusted model: Δ LFn, standardized regression coefficient (β) = -0.528, p = 0.019; Δ LF/HF, β = -0.643, p = 0.001] whereas a greater response to a parasympathetic challenge predicted a lesser decline in executive functioning (adjusted model: Δ LFn, β = -0.716, p < 0.001; Δ LF/HF, β = -0.935, p < 0.001).

Conclusion: Our findings provide novel insight into the link between HRV and cognition in MCI. They contribute to a better understanding of the heart-brain connection, but will require replication in larger cohorts.

Keywords: autonomic nervous system; cognition; episodic memory; executive function; heart rate variability; longitudinal study; mild cognitive impairment; older adults.