ABSTRACT
Introduction: Resting heart rate (HR) and heart rate variability (HRV) have been linked with cognition in the general population and in older individuals. The knowledge of this aspect of heart-brain relationship is relatively absent in older individuals with early Alzheimer's disease (AD) pathology. This study explores relationships of the HR, HRV, and cognition in cognitively healthy individuals with pathological amyloid/tau ratio (CH-PATs) in cerebral spinal fluid (CSF) compared to those with normal ratio (CH-NATs). Methods: We examined therelationshipsbetween1) resting HR and Mini-Mental State Examination (MMSE); 2) resting HR and brain processing during Stroop interference; and 3) resting vagally mediated HRV (vmHRV) and task switching performance. Results: Our studies showed that compared to CH-NATs, those CH-PATs with higher resting HR presented with lower MMSE, and less brain activation during interference processing. In addition, resting vmHRV was significantly correlated with task switching accuracy in CH-NATs, but not in CH-PATs. Discussion: Thesethreedifferenttestsindicatedysfunctionalheart-brainconnections in CH-PATs, suggesting a potential cardio-cerebral dysfunctional integration.
ABSTRACT
BACKGROUND: The CSF amyloid to tau ratio can isolate cognitively healthy participants into normal Aß42/tau (CH-NAT) or a pathological Aß42/tau (CH-PAT) with a low or high risk of cognitive decline, respectively. We aim to determine if plasma Aß42/tau ratios can differentiate CH-NAT from CH-PAT participants. METHOD: Study participants (> 65 years of age) were recruited, and demographic, neurological, and neuropsychological data were obtained in an ongoing HMRI Brain Aging study. Overnight fasting plasma and CSF were collected within a month of examination, and the levels of Aß38, Aß40, Aß42 (MSD 6E10 kit), and total tau were quantified using the MSD electrochemiluminescence platform. Differences in fluid biomarker levels and the plasma ratios (n = 55) and CSF ratios (Aß42/Aß40, n = 41, Aß42/tau, n = 55) were determined using nonparametric student t-test and correlations using a Spearman test. RESULT: Aß40 and Aß42 levels were higher (15-18-fold, and 10-14-fold, respectively), while tau levels are 8-13-fold higher in CSF than in plasma. Plasma and CSF Aß40 were not distinct in CH-NAT compared with CH-PAT. In contrast, Aß42 levels were 30.9% lower in CH-PAT (16.3 ± 18.3 pg/ml) compared with CH-NAT plasma (23.6 ± 26.4 pg/mL) (p < 0.05). CSF Aß42 levels in CH-PAT (171.6 ± 124.6 pg/mL) were lower by 47.6% compared with CH-NAT (327.6 ± 182.6 pg/ml) (p < 0.0001). The Aß42/Aß40 ratio was significantly lower in both plasma and CSF (Table 1A). Similarly, the Aß42/tau ratio was significantly lower in plasma and CSF (Table 1B). Individually, plasma levels of Aß42 and tau did not correlate with CSF levels. However, the ratio of Aß42 to total tau in plasma significantly correlated with the CSF ratios (Spearman r = 0.36, p = 0.0071). Finally, CSF Aß42/Aß40 ratio correlated with Aß42/tau ratio for all samples, CH (n = 100) and MCI (n = 35) (Fig. 1). CONCLUSION: While not as robust as CSF ratios, plasma Aß42/Aß40 and Aß42/tau ratios can isolate cognitively healthy participants with lower risk from participants with a higher risk of cognitive decline. Thus, plasma represents a less invasive medium for the biomarker classification of aging participants.
