Claudia Cantini

Effects of Low Blood Pressure in Cognitively Impaired Elderly Patients Treated With Antihypertensive Drugs

IMPORTANCE The prognostic role of high blood pressure and the aggressiveness of blood pressure lowering in dementia are not well characterized. OBJECTIVE To assess whether office blood pressure, ambulatory blood pressure monitoring, or the use of antihypertensive drugs (AHDs) predict the progression of cognitive decline in patients with overt dementia and mild cognitive impairment (MCI). DESIGN, SETTING, AND PARTICIPANTS Cohort study between June 1, 2009, and December 31, 2012, with a median 9-month follow-up of patients with dementia and MCI in 2 outpatient memory clinics. MAIN OUTCOMES AND MEASURES Cognitive decline, defined as a Mini-Mental State Examination (MMSE) score change between baseline and follow-up. RESULTS We analyzed 172 patients, with a mean (SD) age of 79 (5) years and a mean (SD) MMSE score of 22.1 (4.4). Among them, 68.0% had dementia, 32.0% had MCI, and 69.8% were being treated with AHDs. Patients in the lowest tertile of daytime systolic blood pressure (SBP) (≤ 128 mm Hg) showed a greater MMSE score change (mean [SD], -2.8 [3.8]) compared with patients in the intermediate tertile (129-144 mm Hg) (mean [SD], -0.7 [2.5]; P = .002) and patients in the highest tertile (≥ 145 mm Hg) (mean [SD], -0.7 [3.7]; P = .003). The association was significant in the dementia and MCI subgroups only among patients treated with AHDs. In a multivariable model that included age, baseline MMSE score, and vascular comorbidity score, the interaction term between low daytime SBP tertile and AHD treatment was independently associated with a greater cognitive decline in both subgroups. The association between office SBP and MMSE score change was weaker. Other ambulatory blood pressure monitoring variables were not associated with MMSE score change. CONCLUSIONS AND RELEVANCE Low daytime SBP was independently associated with a greater progression of cognitive decline in older patients with dementia and MCI among those treated with AHDs. Excessive SBP lowering may be harmful for older patients with cognitive impairment. Ambulatory blood pressure monitoring can be useful to help avoid high blood pressure overtreatment in this population.

Day Care for older dementia patients: favorable effects on behavioral and psychological symptoms and caregiver stress

To assess the effects of Day Care (DC) on older subjects with dementia and their caregivers.

Excessive vasoconstriction after stress by the aging kidney: Inadequate prostaglandin modulation of increased endothelin activity

The adaptive capacity of the aging kidney to stimulation of the sympathetic nervous system, as induced by a 30-minute mental stress (MS), was assessed in 8 elderly healthy women (68 to 82 years of age) and compared with that of 8 younger women (24 to 40 years of age). The study encompassed 4 consecutive 30-minute periods (baseline, mental stress, recovery 1, and recovery 2). In the elderly subjects, baseline effective renal plasma flow (ERPF)(iodine 131-labeled hippurate clearance) was lower and glomerular filtration rate (GFR)(iodine 125-labeled iothalamate clearance) was proportionally less reduced than in the younger group; the filtration fraction (FF) was higher. The elderly group excreted more endothelin 1 (ET-1) (P < .05), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1alpha (6-keto PGF1alpha)(P < .001 for both)(radioimmunoassay). Mental stress induced similar increases in blood pressure, heart rate, and plasma catecholamines in the 2 age groups, limited to the stimulation period. In the elderly group, mental stress caused a prolonged decrease in ERPF that reached its maximum 60 minutes after mental stress (-33%, P < .05), while GFR remained constant during the whole experiment, so that FF increased. In the younger subjects, renal hemodynamic changes were limited to the mental stress period. ET-1 increased during mental stress and the first recovery period in the elderly group (+50% and +25%, P < .05) as it did in the younger group, but the elderly group differed from the younger in that vasodilating prostaglandins increased only during mental stress. In conclusion, the aging kidney reacts to adrenergic stimulation with more-pronounced and -prolonged vasoconstriction that is probably caused by a defect in prostaglandin modulation of endothelin activity. Autoregulation of GFR is maintained at the expense of increased intraglomerular pressure.

Increased renal formation of thromboxane A 2 and prostaglandin F 2α in heart failure

Renal formation of the vasoconstrictor prostaglandins thromboxane A 2 (TXA 2 ) and prostaglandin F 2α (PGF 2α ) was investigated in 25 patients with cardiac failure, divided into New York Heart Association functional classes I to IV, and in eight healthy control subjects. Plasma renin activity (PRA) and hemodynamic parameters were also investigated. Renal vasoconstrictor eicosanoid formation, measured in urinary daily excretion, was not different between patients in class I and control subjects. Class II to IV patients showed progressively increasing production of PGF 2α (F = 49.8, p < 0.001, analysis of variance) and TXA 2 (F = 37.8, p < 0.002). PGF 2α excretion peaked in class IV (+1266% vs class I, p < 0.001). Compared with class I, urinary excretion of thromboxane B 2 was +816% in class III and +1561% in class IV (both p < 0.001). PRA was significantly increased only in class IV (+1558%, p < 0.001). The current results indicate a progressive increase in renal production of vasoconstrictor eicosanoids directly related to New York Heart Association class and suggest that these prostanoids may have a role in deterioration of renal function. (Am Heart J 1997;133:94-100.)

Renal adaptation to stress: A possible role of endothelin release and prostaglandin modulation in the human subject

The aim of this study was to define the neurohumoral response associated with the renal hemodynamic perturbations induced by mental stress acting as an adrenergic stimulus. In 8 healthy women, the effects of mental stress were studied during four consecutive 30-minute periods (baseline, mental stress, recovery I, recovery II). Mental stress induced sympathetic activation as evidenced by increases in blood pressure, heart rate, and plasma norepinephrine level. Effective renal plasma flow (iodine 131-labeled hippurate clearance) decreased only during mental stress (-22%, p < 0.05 vs baseline); glomerular filtration rate (iodine 125-labeled iotalamate clearance) remained constant during the entire experiment; the filtration fraction increased significantly during mental stress and recovery I (+30% and +22%, respectively, p < 0.02 for both). Complex neuroendocrine responses were associated with the hemodynamic changes. Urinary excretion of endothelin-1 and 6-keto-PGF(1alpha) increased during mental stress (+53%, p < 0.01, and +20%, p < 0.01, respectively) and recovery I (+49% and +29%, respectively, p < 0.01 for both). Urinary cyclic guanosine monophosphate rose only during mental stress (+77%, p < 0.05), whereas excretion of PGE2 showed a stepwise increase throughout recovery I and II (+292%, p < 0.01, and +360%, p < 0.001, respectively). In conclusion, the present experiments demonstrate that renal hemodynamic response induced by mental stress is a complex reaction in which endothelin-1, prostaglandins, and presumably nitric oxide take part.

Impaired Renal Adaptation to Stress in the Elderly With Isolated Systolic Hypertension

The aim of this study was to evaluate the renal response in the elderly with isolated systolic hypertension (ISH) when an adrenergic activation, as induced by mental stress, is applied. Renal hemodynamics and kidney neurohumoral response to mental stress were studied in 8 elderly patients with ISH (aged 63 to 82 years) along with 8 elderly normotensive subjects. The study encompassed four 30-minute experimental periods (baseline, mental stress, and recovery I and II). In these patients, the mental stress-induced blood pressure rise was associated with a significant increase in both effective renal plasma flow ((131)I-labeled hippurate clearance) and glomerular filtration rate ((125)I-labeled iothalamate clearance) (+42% and +29%, respectively; P<0.01 for both), without variations in filtration fraction, while elderly normotensives reacted to adrenergic stimulation with renal vasoconstriction but with the glomerular filtration rate constant. Variations in renal vasoactive substances, which paralleled hemodynamics of the kidney, differed in the 2 groups. In normotensives, excretion (radioimmunoassay) of endothelin-1, prostaglandin E(2), and cGMP increased during the stimulus (+50%, +54%, and +59%, respectively; P<0.05). In ISH patients the release of these autacoids did not vary in any of the experimental periods. In conclusion, in patients with ISH the renal adaptive capacity to sympathetic activation is impaired, and the data may suggest that the glomerulus passively suffers the blood pressure increase, probably because of the insufficiency of the neurohumoral response, particularly in regard to the increase of endothelin-1. This hemodynamic pattern may predispose ISH patients to a higher risk of renal injury.

Changes in renal autacoids and hemodynamics associated with aging and isolated systolic hypertension

The aging kidney is characterized by a decrease in renal blood flow and glomerular filtration rate mainly due to glomerulosclerosis. Nevertheless, even in the presence of these changes, the kidney maintains its functionality until advanced age. However, there is a tendency towards greater renal vasoconstriction in the elderly as compared with young individuals. This occurs either in physiological circumstances such as physical exercise, or in disease manifestations, such as the effective circulatory volume depletion that develops, for example, in heart failure. This tendency may be secondary to the reduction of renal autacoid modulatory capacity, particularly at the vasodilating prostaglandin level. In an acute experimental model we could demonstrate that, in the healthy elderly, the renal response to adrenergic activation by mental stress is characterized by a prolonged and pronounced vasoconstriction. In addition to this, in elderly patients affected by isolated systolic hypertension, we demonstrated an impairment of renal hemodynamic and humoral adaptation capacity in response to adrenergic activation and blood pressure increase. In the presence of sudden blood pressure increase, the kidney of these patients responds with a passive vasodilation and a glomerular filtration rate increase without any activation of humoral modulatory substances. The impairment in renal adaptation capacity may predispose these patients to renal injury, particularly in the presence of the many hypertensive peaks which characterize everyday life of elderly individuals. In conclusion, these results show that renal adaptation capacity of elderly patients with isolated systolic hypertension is completely lost. Further studies will elucidate whether antihypertensive treatment per se, or specific classes of antihypertensive drugs, are able to revert this impairment.

Tolerability of ambulatory blood pressure monitoring (ABPM) in cognitively impaired elderly

Abstract Objective: Recent guidelines have widened clinical indications for out-of-office blood pressure measurement, including home blood pressure monitoring and ambulatory blood pressure monitoring (ABPM), suggesting the latter as recommended method in cognitively impaired patients. There is, however, a widespread belief that ABPM could be poorly tolerated in dementia, often leading to withdraw from its use in these patients. Aim: To assess the actual tolerability of ABPM in a group of cognitively impaired elderly, affected by dementia or mild cognitive impairment (MCI). Methods: We evaluated 176 patients aged 65 + years, recruited in two different memory clinics, with a Mini Mental State Examination (MMSE) between 10 and 27. Behavioral and psychological symptoms were assessed with Neuropsychiatric Inventory (NPI). A patient was considered tolerant if able to keep the device on continuously for 24 h. The minimum number of correct measurements required was 70% of the predicted total number. Results: 16% of patients wore the device for less than 24 h. Dividing the study population in tertiles of MMSE performance, 29% failed to tolerate the device in the lowest, 12% in the middle and 7% in the highest tertile (p < 0.01). Dividing the study population in tertiles of NPI performance, 30% of patients failed in the highest, 19% in the middle and 8% in the lowest tertile (p = 0.02); 31% of patients who tolerated the device did not achieve the minimum number of measurements required, with a mean number of 63% of predicted measurements. Conclusion: The ABPM proved a generally well-tolerated technique even in cognitively impaired elderly. Only a minority of subjects with poorer cognitive performances and greater behavioral symptoms did not tolerate the monitoring. Among most patients who failed to achieve the minimum number of measurements needed, the number of valid measurements was very close to the minimum required.

Recent Aspects of Renal Pathophysiology in the Elderly

The aging kidney is characterized by both anatomical and functional changes. However, renal modifications that are currently observed in the elderly are often due not only to the physiological renal senescence but also to the overlapping of various pathological conditions that may be subclinical or unrecognized. Therefore the present chapter will deal with the consequences of physiological aging of the kidney and the reasons will be examined why these modifications in the elderly are capable of conditioning a different reaction in the presence of a stressful or pathological situation in respect to the young.