Hypertension and Neuropsychiatric Symptoms in Patients with Drug-Naïve Alzheimer's Disease

Abstract

INTRODUCTIONHypertension and dementia are common diseases in the elderly population. Approximately 8-10% of people age 65 or older suffer from dementia and 65% suffer from hypertension. 1,2 In recent epidemiological studies, vascular risk factors have been associated with Alzheimer's disease (AD) as well as vascular dementia. In particular, hypertension is a major vascular risk factor, and studies on the relationship between hypertension, cognitive dysfunction, and onset of dementia are actively underway. Some cross-sectional observational studies have reported cognitive decline occurs frequently when blood pressure (BP) is high, especially when uncontrolled.3 Other studies have reported hypertension and cognitive function are correlated as U-curves, and that both very high and very low BP increase cardiovascular disease and consequently cognitive decline. 4,5 In most follow-up studies, middle-aged hypertension was an independent risk factor for senile cognitive impairment and dementia. [6][7][8][9] However, little is known about the relationship between modifiable risk factors and neuropsychiatric symptoms (NPS) in AD. Vascular risk factors, such as hypertension, hyperlipidemia, and stroke, are of interest because they are risk factors for NPS among individuals without AD. 10 We investigated prevalence of NPS and the degree of Korean version of Neu- Background and Purpose Neuropsychiatric symptoms (NPS) such as anxiety, depression, and delusions affect up to 90% of all patients with Alzheimer's disease (AD). NPS is associated with significant caregiver burden and patient distress. Given the severe burden of NPS in AD, it is critical to know potential modifiable risk factors of NPS in AD. This study explores the association between hypertension and NPS in patients with drug-naïve AD.Methods We reviewed medical records of 149 patients with AD with (n=80) and without (n=69) hypertension. NPS were assessed using the Korean version of Neuropsychiatric Inventory (K-NPI). Affective, psychotic, and behavior symptom clusters were assessed separately.Results The total score of K-NPI was not significantly different between patients with AD with and without hypertension. Among K-NPI domains, scores of depression/dysphoria (p=0.045), anxiety (p=0.022), and apathy/indifference (p=0.037) were significantly higher in patients with AD with hypertension. Systolic blood pressure (BP) was associated with higher total K-NPI and affective symptom cluster scores. Diastolic BP was associated with affective symptom cluster scores.Conclusions Results suggest that hypertension increases risk of specific NPS in patients with AD. Among NPS, hypertension was associated with affective symptom cluster.

White matter lesions and temporal atrophy are associated with cognitive and neuropsychiatric symptoms in patients with hypertension and Alzheimer's disease

“…Behavioral differences between patients with and without HTN were also observed in specific items of NPI such as delusions, depression, anxiety, apathy, disinhibition, irritability, and nighttime behaviors. This finding is consistent with the results of some studies that have found that a history of HTN increases the risk of BPSD such as depression/dysphoria, anxiety, and apathy in AD patients 34,35 . In a study of older AD patients, VRFs were associated with a greater risk of delusion, depression, and agitation 36 .…”

“…This finding is consistent with the results of some studies that have found that a history of HTN increases the risk of BPSD such as depression/dysphoria, anxiety, and apathy in AD patients. 34,35 In a study of older AD patients, VRFs were associated with a greater risk of delusion, depression, and agitation. 36 suggesting that the degeneration of the medial temporal lobe may be closely correlated with the emergence of some BPSD.…”

Neuropsychiatric Inventory domains cluster into neuropsychiatric syndromes in Alzheimer's disease: A systematic review and meta‐analysis

“…The results of our systematic search are summarized in Figure 1 , according to the preferred reporting items for systematic reviews and meta‐analyses (PRISMA) guidelines (Page et al., 2021 ). In total, 25 studies were included in the systematic review (Aalten et al., 2007 ; Archer et al., 2007 ; Chen et al., 2012 ; Connors et al., 2018 ; Cummings et al., 2006 ; Dennehy et al., 2013 ; Frisoni et al., 1999 ; Garre‐Olmo et al., 2010 ; Gauthier et al., 2005 ; Germain et al., 2009 ; Hollingworth et al., 2006 ; Hwang et al., 2017 ; Kang et al., 2010 ; Kazui et al., 2016 ; Kim et al., 2021 ; Matsui et al., 2006 ; Mirakhur et al., 2004 ; Nagata et al., 2016 ; Poletti et al., 2013 ; Proitsi et al., 2011 ; Scassellati et al., 2020 ; Spalletta et al., 2010 ; Starr & Lonie, 2007 ; Vilalta‐Franch et al., 2010 ; Wang et al., 2012 ). The characteristics of these studies are summarized in Supplemental Material 1 .…”

“…The mean study age ranged from 72 to 84 years. The percentage of female participants ranged from 50.3% (Connors et al., 2018 ) to 78.1% (Chen et al., 2012 ), and the mean mini‐mental state examination (MMSE) ranged from approximately 8 (Gauthier et al., 2005 ) to 23 (Hwang et al., 2017 ) points. The studies represented a wide range of geographic regions including Asia ( n = 7, including Japan, Mainland China, South Korea, and Taiwan [Republic of China]), Australia ( n = 1), Europe ( n = 13, including England, Greece, Italy, Northern Ireland, Republic of Ireland, Scotland, Spain, and Wales), and North America ( n = 4 from the United States).…”

“…The percentage of female participants ranged from 50.3% (Connors et al, 2018) to 78.1% (Chen et al, 2012), and the mean mini-mental state examination (MMSE) ranged from approximately 8 (Gauthier et al, 2005) to 23 (Hwang et al, 2017) The majority of studies used the NPI-12(16/25; 64%). Most studies (18/25; 72%) used PCA as their primary method of analysis to draw conclusions on the factor structure of the NPI (Aalten et al, 2007;Archer et al, 2007;Chen et al, 2012;Cummings et al, 2006;Frisoni et al, 1999;Gauthier et al, 2005;Germain et al, 2009;Hollingworth et al, 2006;Kazui et al, 2016;Kim et al, 2021;Matsui et al, 2006;Mirakhur et al, 2004;Nagata et al, 2016;Poletti et al, 2013;Scassellati et al, 2020;Spalletta et al, 2010;Vilalta-Franch et al, 2010), followed by CFA (5/25; 20%; Connors et al, 2018;Dennehy et al, 2013;Garre-Olmo et al, 2010;Kang et al, 2010;Proitsi et al, 2011), and EFA (2/25; 8%; Hwang et al, 2017;Wang et al, 2012). The number of factors identified ranged from three to five with most studies supporting a three-factor (11/25; 44%) structure followed by a four-factor (9/25; 36%) and five-factor (5/25; 20%) structure.…”