Association Between Heart Rate Variability and Cognitive Function in Elderly Community‐dwelling Men Without Dementia: A Preliminary Report

To the Editor: Prior studies have demonstrated that heart rate variability (HRV) analysis, a noninvasive approach to measuring autonomic function, is useful in assessing autonomic abnormalities in various types of dementia.1-6 These reports have supported the association between cognitive impairment and autonomic dysfunction in patients with dementia, but such association is unclear in elderly subjects without clinical dementia. Therefore, in this study, the HRV analysis was applied to examine the association between autonomic and cognitive functions in an elderly population without dementia. Sixty-three elderly Chinese subjects without dementia were recruited from public veterans housing in the community (mean age±standard deviation 78.3±3.9, range 72–92; mean years of education 7.1±4.6, range 0–16). Informed consent was obtained from all subjects before commencement of the study. Each subject was carefully evaluated for medical and psychiatric illness to exclude the presence of possible dementia (Clinical Dementia Rating Scale score >0), presence of other mental illness, chronic medical illness, and neurological disorders. A group of elderly subjects without dementia and with normal function in daily activities was included in this study. Cognitive function was assessed using the Cognitive Abilities Screening Instrument (CASI).7 CASI was designed to cover a larger domain of cognitive functions and may provide more power than the Mini-Mental State Examination in identifying subtle cognitive decline in elderly subjects.8 The total CASI score ranges from 0 to 100. In this study, a validated Chinese version of the CASI scale (CASI C-2.0) was employed (mean 87.0±5.1, range 76–97).9 Electrocardiogram monitoring took place in the daytime, and participants were asked to avoid smoking and exercise. A Holter monitor (E3-8010 Portable Recorder, Microstar Inc., Taipei, Taiwan) was used to obtain 2 hours of ambulatory electrocardiogram recordings. HRV measures covering time, frequency, and nonlinear domain were used in analyzing interbeat interval time series according to international guidelines.10 Multiple linear regression analysis was applied to determine the association between HRV indices and cognitive measures with adjustment for age and education level. Partial and unadjusted Pearson correlation coefficients are shown in Table 1. Significantly positive correlations were found between adjusted CASI and standard deviation of normal interbeat intervals (SDNN, correlation coefficient (r)=0.37, P=.004), standard deviation of averages of normal interbeat intervals in all 5 minutes segments (SDANN, r=0.36, P=.005), and very low frequency power (VLF, r=0.29, P=.03). Furthermore, three components of adjusted CASI were significantly associated with certain HRV indices. Short-term memory was correlated with the root mean square of difference of consecutive interbeat intervals (RMSSD, r=0.26, P=.04), attention was correlated with high-frequency power (HF, r=0.27, P=.03), the fraction of consecutive interbeat intervals differed by more than 20 ms (pNN20, r=0.28, P=.03), and list-generating fluency was correlated with SDNN and SDANN (r=0.29, P=.03; r=0.30, P=.02, respectively). None of the nonlinear HRV indices applied in this study were significantly correlated with cognitive measures. This study indicated the following two key results. (1) The overall HRV, as measured using SDNN, SDANN, and VLF, was positively correlated with CASI score in elderly subjects without dementia. (2) Certain HRV variables, including RMSSD, pNN20, HF, SDNN, and SDANN, were positively correlated with individual components of CASI related to short-term memory, attention, and list-generating fluency. The novel finding of this study was that low HRV was associated with subtle cognitive decline in elderly subjects without dementia. The aging process, which is known to contribute to cognitive impairment and loss of HRV, may explain this preliminary result. Furthermore, biological mechanisms may provide an explanation of the association between essential cognitive functions (attention and short-term memory) and parasympathetic-related HRV indices, namely RMSSD, pNN20, and HF. The cholinergic system is critical to the integrity of autonomic and cognitive function. Dysfunction of the cholinergic system may not only impair cognitive functions but also decrease the cardiac innervation of the parasympathetic system.2 The relatively small sample of subjects limited this study, as did the fact that it included only men. Although cases of dementia were carefully excluded based on clinical assessment, mild cognitive impairment may have been present in this study sample. It is unclear whether subjects in this study with mild cognitive impairment will develop dementia in the near future. Further longitudinal follow-up is needed to confirm the findings. Moreover, genetic and imaging studies are warranted to investigate the neurobiology of the cholinergic system in the association between autonomic and cognitive function during the normal aging process. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the author and has determined that none of the authors have any financial or any other kind of personal conflicts with this letter. This study was supported by the National Science Council of Taiwan (NSC 95-2314-B-075-111) and the Taipei Veterans General Hospital (V95ER3-003 and V96ER3-002). Author Contributions: ACY and SJT contributed equally to this work. ACY, SJT: conception and design. CHH, MEL: acquisition of data. ACY, SJT: analysis and interpretation of data. ACY: drafting of the manuscript. ACY, SJT: critical revision of the manuscript for important intellectual content. ACY: statistical analysis. CHY, SJT: obtaining funding. SJT, CJH, CHY: administrative, technical, or material support. SJT: supervision. Sponsor's Role: The funding organizations had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the letter.