Several cardiovascular indices, such as blood pressure (BP), heart rate (HR), and heart rate variability (HRV), are predictors of vascular disease risk in the elderly. It has not yet been shown, however, how these indices are associated with maintained cognitive function. In 2000, we began a community-based study to longitudinally investigate the longevity and aging in Hokkaido County (LILAC) [1–5] and to evaluate the population’s neurocardiological function. Our goal was the prevention of stroke and the decline in cognitive function of the elderly in a community dwelling.

We initially examined 115 people older than 75 years (average, 79.6 years). BP was measured at the beginning of study in a sitting position, and pulse wave velocity (PWV) was measured between the right arm and ankle in a supine position, using an ABI/form instrument (Nippon Colin Co., Ltd., Komaki, Japan). The first 1 hour of ambulatory ECG recording was obtained during routine medical examination conducted each year in July. The data were processed for HRV using a Fukuda-Denshi Holter analysis system (SCM-280-3). Time-domain measures (SDNN, pNN50, SDANN, and Lorenz plot indices: length (L), width (W), and L/W ratio) and frequency-domain measures were determined, namely the spectral power in the very low frequency (VLF), 0.003–0.04 Hz; low frequency (LF), 0.04–0.15 Hz; and high frequency (HF), 0.15–0.40 Hz regions and the LF/HF ratio. Except for SDNN and HR, calculated over the whole 1-hour record, all indices were computed as averages over consecutive 5-min intervals. Spectral indices were obtained by the maximum entropy method (MEM) with the MemCalc/CHIRAM program (Suwa Trust Co., Ltd., Tokyo, Japan).

Using as reference the data obtained in July 2000, the cardiovascular coordination function of each participant was scored as 3, 2, or 1 point for each of the following three indices (systolic BP, HR, and VLF component of the HRV): systolic BP > 160, 140–159, or < 140 mmHg; HR > 80, 70–79, or < 70 beats/min; and VLF < 800, 800–1000, or > 1000 msec².

Participants were classified into either the normal, mildly disordered, or disordered group when the sum of these indices was ≤ 4, 5 or 6, or ≥7, respectively.

The Japanese version of the Mini-Mental State Examination (MMSE) and the Hasegawa Dementia Scale Revised (HDSR) was used to measure the overall cognitive function, including verbal orientation, memory, and constructional ability. The Up & Go test measured, in seconds, the time it took the subject to stand up from a chair, walk a distance of 3 m, turn, walk back to the chair, and sit down again. This test is a simple measure of physical mobility and demonstrates the subject’s balance, gait speed, and functional ability (Up & Go). A lower time score indicates better physical mobility. Functional reach, used to evaluate balance, represents the maximal distance a subject can reach forward beyond arm’s length while maintaining a fixed base of support in the standing position. A higher score indicates better balance. Manual dexterity was assessed using a panel with combinations of ten hooks, ten big buttons, and five small buttons. Three discrete measurements of time were recorded for each participant (ten “hook-ons”, ten big “button-on-and-offs”, and five small “button-on-and-offs”). Total manual dexterity time in seconds, defined as the button score (Button-S), was calculated by adding the average times for one hook-on and one big or small button-on-and-off. A lower button score indicates better manual dexterity.

In 2000 (reference), the cardiovascular coordination score did not correlate with any index of neurobehavioral function, although it showed a negative correlation with SDNN, SDANN, pNN50, LF, or HF components (p<0.0001) and a positive correlation with baPWV (p<0.01). We were able to follow-up 72 of the 115 subjects.

We found that between 2000 and 2002, the cognitive function, estimated by MMSE and HDSR, was maintained or improved as follows: In the cardiovascular coordination disordered group, MMSE and HDSR improved from 24.6 to 26.0 (p = 0.06) and from 23.8 to 25.9 (p = 0.04), respectively. In the mildly disordered group, these indices improved from 23.4 to 25.7 (p = 0.005) and from 23.4 to 25.1 (N.S.), respectively. In the normal cardiovascular coordination group, MMSE and HDSR were maintained from 25.6 to 26.0 (N.S.) and from 24.9 to 26.4 (N.S.), respectively. There were no statistically significant alterations in activities of daily living (ADL), assessed by Up & Go, functional reach, and button score, in any of the groups.

Although a cross-sectional study did not show any apparent correlation between cardiovascular and neurobehavioral functions in subjects 75 years of age or older, an intervention aimed at preventing stroke and a decline in cognitive function in an elderly community-dwelling population induced an improvement of the cognitive function, especially in people suffering from hypertension, tachycardia, or decreased HRV. In conclusion, this study demonstrates a positive impact of a simple social intervention, including advising medical prescription, in improving a disordered cognitive function in elderly people. It is noteworthy that people with a disordered coordination of cardiovascular function are more sensitive to such an intervention, suggesting that the cardiovascular function is a major factor affecting cognitive function.

We elucidated the predictive value of comprehensive geriatric assessment (CGA) including heart rate variability and arterial stiffness on the risk of cerebral cardiovascular death, decline of motor function, and cognitive impairment in the LILAC study.

The LILAC study was conducted from July 2000 to November 2005 in 272 persons older than 75 years (female ratio was 59.6 %, average age was 79.1±4.7 years, hypertension was 53.0 %, diabetes mellitus was 14.7 %, and dyslipidemia was 47.0 %). Medical examination and CGA involved cognitive function assessments including MMSE, HDSR, and Kohs block test and ADL assessments including the Up & Go test, functional reach test (FR), and button test, and geriatric depression scale consultations were performed every year (Table 10.1). Heart rate variability (HRV) and arterial stiffness measurement including brachial-ankle PWV (baPWV) and ankle-brachial pressure index were evaluated.