HomeLarge Type Edition
HOME ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Services
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
PubMed
Right arrow PubMed Citation
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 60:67-73 (2005)
© 2005 The Gerontological Society of America

Cross-Sectional and Longitudinal Association Between Antihypertensive Medications and Cognitive Impairment in an Elderly Population

Ihab Hajjar1,2,, Heath Catoe2, Sherry Sixta2, Rebecca Boland1,2, David Johnson1,2, Victor Hirth1,2, Darryl Wieland1,2 and Paul Eleazer2

1 Palmetto Health Richland Senior Primary Care Practice, Columbia, South Carolina.
2 Division of Geriatrics, Department of Medicine, University of South Carolina, School of Medicine, Columbia.

Address correspondence to Ihab Hajjar, MD, MS, Clinical Assistant Professor of Internal Medicine, Division of Geriatrics, Department of Medicine, Palmetto Health Richland, University of South Carolina, School of Medicine. E-mail: ihab.hajjar{at}palmettohealth.org


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
Background. The effect of antihypertensive medications on cognitive function has not been well studied. The authors' objectives were to investigate the cross-sectional and longitudinal association between the use of antihypertensive medications and cognitive function and to compare different antihypertensive medication classes with regard to this association in an elderly population.

Methods. The medical records of a convenience sample of patients (n = 993 cross-sectional and 350 longitudinal; mean age, 76.8 ± 0.3 years; 74% women; 87% White) followed at a geriatric practice were reviewed. Data abstracted included demographics, medical history (Alzheimer's disease [AD] or vascular dementia [VaD]), use of antihypertensive medications, and results of cognitive assessments (the Mini-Mental Status Examination [MMSE] and the Clock Draw Test [CDT]).

Results. In the cross-sectional analysis, antihypertensive use was not associated with MMSE (p >.05), CDT (p >.05), or dementia diagnosis (odds ratio for AD, 0.8; 95% confidence interval [CI], 0.6 to 1.2; odds ratio for VaD, 1.6; 95% CI, 0.6 to 4.0). In the longitudinal analysis, antihypertensive use was associated with a lower rate of cognitive decline on the MMSE (–0.8 ± 2 points in users vs –5.8 ± 2.5 points in nonusers; p =.007) and on the CDT (–0.3 ± 0.8 points in users vs –2.2 ± 0.8 points in nonusers; p =.002), and with a lower risk for the development of cognitive impairment (odds ratio, 0.56; 95% CI, 0.38 to 0.83; p =.004). The trend was similar in patients with baseline AD (p =.02). Patients taking diuretics (p =.007), angiotensin-converting enzyme inhibitors (p =.016), and beta-blockers (p =.014) had a lower rate of cognitive decline, and patients taking angiotensin receptor blockers (p =.016) had improved cognitive scores.

Conclusions. Antihypertensive use, particularly diuretics, angiotensin-converting enzymes inhibitors, beta-blockers, and angiotensin receptor blockers, may be associated with a lower rate of cognitive decline in older adults, including those with AD. Until a randomized clinical trial confirms our results, findings of this observational study should be interpreted with caution.

DEMENTIA is a devastating illness that affects at least 4 million persons in the United States (1). Although few treatments have been developed that would decrease the progression of this illness, prevention remains the most effective approach. Evidence from observational studies suggests that elevated blood pressure is a risk factor for cognitive impairment and the development of dementia (2). In the Honolulu-Asia Aging Study, midlife higher systolic blood pressure was associated with an increased risk for late life poor cognitive function (3). In addition, in a recent prospective population survey, high midlife systolic blood pressure was associated with an increased risk for Alzheimer's disease (AD) (4). This association has been documented in different populations (5–8), in persons with and without cerebrovascular disease (9), and in persons with AD (5,10). Interestingly, longitudinal surveys have suggested that blood pressure decreases in the period immediately preceding the onset of cognitive impairment (5). The decline seen immediately before the onset of cognitive decline may explain the conflicting results seen in cross-sectional case control studies (9,11–16).

It is possible, then, that pharmacologic measures to lower blood pressure may preserve function and decrease the risk for dementia. The evidence, however, has been conflicting. In 1987, Larson and colleagues (17) reported that persons who receive antihypertensive medications demonstrated global cognitive impairment. However, other cross-sectional and longitudinal studies have shown that use of antihypertensive medication is associated with preservation of cognitive function (8,18,19). Randomized clinical trials have also found conflicting results. For example, in the Systolic Hypertension in the Elderly Program, no difference in cognitive decline or the onset of dementia occurred between treated and untreated participants (20). In the Systolic Hypertension in Europe trial, however, treatment of hypertension was associated with a 50% decline in dementia incidence (21,22). These conflicting findings could be related, in part, to the use of different classes of antihypertensive medications. The comparative effect of the different classes of antihypertensive medications on cognition and dementia in the same population is not known.

In this study, our primary objective was to investigate the cross-sectional and longitudinal association between the use of antihypertensive medications and cognitive function in an elderly population. Our secondary objective was to compare different antihypertensive classes with regard to this association.


   METHODS
Top
 Abstract
 Methods
Results
 Discussion
 References
 
We performed a cross-sectional and retrospective cohort study with repeated measures on a cohort of patients followed at the Palmetto Health Richland Senior Primary Care Practice, a community-based academic primary care geriatric practice in Columbia, South Carolina, founded in 1997. All practice physicians specialize in internal medicine (n = 5) or family practice (n = 1) and are fellowship-trained geriatricians. They provide diagnostic and therapeutic services to the participants and are responsible for the documentation of medical history in the patients' records. As part of the usual care provided in this practice, trained staff directly examine each patient's medication bottles during each visit. One day before their visit, patients are reminded by telephone to bring all their prescription and over-the-counter medication bottles with them. Staff members who are annually trained to measure blood pressure according to the American Heart Association standards measure patient blood pressure during each clinical encounter. All patients are offered yearly cognitive assessments via two standardized tools, the Mini-Mental Status Examination (MMSE) (23) and the Clock Draw Test (CDT) (24), which are administered by trained geriatric social workers. Medical records are maintained in accordance with hospital requirements. We selected our participant sample serially (using the medical record numbers) from the overall Senior Primary Care Practice patients (n = 2500). We included patients if they had been assessed with at least one cognitive test.

A medical student (S.S.) and a graduate student (H.C.) abstracted data from the initial and follow-up visits from the records. These data included the date of the visit, demographic and anthropometric information, sitting blood pressure measurements, educational level, family history, tobacco and alcohol use, clinical diagnoses, antihypertensive medication use, results of cognitive testing, and laboratory information including serum cholesterol and low-density and high-density lipoprotein levels. The database manager (R.B.) developed data extraction forms, and data entry was performed under the supervision of a geriatrician (I.H.). We considered that patients had hypertension if they were receiving antihypertensive medications or had a systolic blood pressure of 140 mmHg or greater or a diastolic blood pressure of 90 mmHg or greater. We considered patients to have treated hypertension if they were receiving any antihypertensive medication. We also abstracted dementia diagnosis and its subtypes, when available (AD and vascular dementia [VaD]), from the records. We considered patients to have developed cognitive impairment if they had an MMSE score less than 24 or a clinical diagnosis of dementia at follow-up but not at baseline (25). We performed cross-sectional analyses using data abstracted from the initial visit. We conducted longitudinal analyses, using data from the follow-up visits, only on those with more than one cognitive testing score.

We determined the patients' use of antihypertensive medications from the clinician's documentation, staff medication review, and written or called-in prescriptions. We separated drugs into nine classes: diuretics, angiotensin-converting enzyme inhibitors (ACE), beta-blockers (BB), alpha-blockers, angiotensin receptor blockers (ARB), dihydropyridine calcium channel blockers, non-dihydropyridine calcium channel blockers, clonidine, and others. We coded combination drugs individually as two separate antihypertensive classes. We assigned patients to each class if they were using the corresponding antihypertensive drug at baseline or during the follow-up period. In addition, we noted any change in antihypertensive class or the addition of a different antihypertensive class.

We performed multivariate analyses using the mixed model theory for repeated measures (26–28). This procedure is used with unbalanced data, incorporates longitudinal change in predictor variables such as blood pressure, body mass index, age, and drug exposure, and is less likely to be affected by missing data (29). The outcome measures we used were serial MMSE and CDT scores. We adjusted the multivariate models for the following covariates: age, sex, ethnicity, anthropometrics, diagnosis of stroke or diabetes mellitus during the follow-up period, serial blood pressure readings, cholesterol, low-density and high-density lipoprotein levels, baseline cognitive test results, alcohol and smoking history, level of education, and family history of dementia or AD. We used the mixed model to compare the rate of decline in cognitive scores in patients receiving and those not receiving antihypertensive medications. In addition, we evaluated the rate of cognitive decline in hypertensive patients using antihypertensive drugs versus those not using antihypertensive drugs, in patients with hypertension receiving antihypertensive medications versus those who were not hypertensive, and in patients with hypertension but not receiving antihypertensive medications versus those who did not have hypertension. We used logistic and multiple regression models for the cross-sectional analyses with similar covariate adjustments. To adjust for the complexity of antihypertensive exposure, we performed analyses using an exposure index that measures the number of days each patient has used the antihypertensive medication class and incorporated that index in all the models. The institutional review board approved the study at the local institution.


   RESULTS
Top
 Abstract
 Methods
 Results
Discussion
 References
 
We abstracted data on a convenience sample of 993 patients (mean age at baseline, 76.8 ± 0.3 years; age range, 38–98 years [11 (1%) were younger than 60 years]; 74% women; 87% White, 11% African American) followed between 1997 and 2002 (the first evaluation was April 1, 1997; the last evaluation was July 1, 2002). Of those, 350 (mean age at baseline, 76.9 ± 0.4 years; age range, 48–96 years; 73% women; 88% White, 11% African American) had serial cognitive testing and were included in the longitudinal analysis (mean follow-up, 24.9 ± 0.7 months; follow-up range, 1–58.8 months, for a total of 724 ± 20 patient-years).

At baseline, 81% patients had hypertension and 54% were receiving antihypertensive medications. In addition, at baseline 213 (24%) patients had clinical diagnoses of dementia (66% AD, 10% VaD), and during the follow-up period, we identified 62 new cases of cognitive impairment. Treated patients were older (p <.05); had higher mean body mass indexes (p <.05); and had a higher prevalence of diabetes mellitus (p <.05) and stroke (p <.05), and lower mean cholesterol level (p <.05) (Table 1). Of those patients taking antihypertensive medications, 297 (54.9%) were receiving one, 183 (33.8%) were receiving two, and 61 (11.3%) were receiving three or more antihypertensive classes (Table 2).


View this table:
[in this window]
[in a new window]
  		Table 1. Baseline and Follow-up Characteristics in the Selected Sample.

 

View this table:
[in this window]
[in a new window]
  		Table 2. Mean Cognitive Scores and Risk of Dementia by Antihypertensive Class in the Cross-Sectional Analysis.

 
In the cross-sectional analysis, we found no difference in mean MMSE score, CDT score, or diagnosis of dementia, AD, or VaD between those receiving and those who were not receiving antihypertensive medications (Table 1). In addition, we observed no differences between nonhypertensive and hypertensive patients who were receiving or not receiving medications (mean MMSE score, 23.9 ± 0.6 vs 24.9 ± 0.5 vs 25.2 ± 6.4 [p =.1]; mean CDT score, 5.1 ± 0.2 vs 5.1 ± 0.1 vs 5.0 ± 0.1 [p =.7] in nonhypertensive patients and in hypertensive patients receiving antihypertensive medications and those not receiving antihypertensive medications, respectively). When we compared the different antihypertensive classes, none was associated with cognitive impairment or risk for dementia, AD, or VaD (Table 2).

In the longitudinal analysis, we found that patients who were receiving antihypertensive medications had a lower rate of decline in cognitive function compared with patients who were not receiving antihypertensive medications. At the last visit, patients receiving antihypertensive medications showed a decline of –0.8 ± 2 points vs –5.8 ± 2.5 points in patients not receiving antihypertensive medications (p =.007) (Figure 1). Compared with the first visit, treated hypertensive patients at the last visit showed a decline of –0.6 ± 0.8 points on the MMSE scale compared with a decline of –4.5 ± 1.8 points in hypertensive patients who were not receiving antihypertensive medications (p =.0004) and –5.9 ± 2.4 in nonhypertensive patients (p =.02). We found no differences in the decline of MMSE scores between nonhypertensive and hypertensive patients who were not receiving medications (p =.4). Treated hypertensive patients also had a lower decline in their CDT scores compared with the other groups (decline of –0.3 ± 0.8 points in those taking antihypertensive medications vs –2.2 ± 0.8 points in those who were not taking antihypertensive medications [p =.002]). We noted a similar pattern in those with and without dementia at baseline and in those with AD (p <.0001, p <.0001, and p =.015 for the difference in cognitive decline on the MMSE in those with and without dementia and with AD at baseline, respectively) (Figure 1). The risk for developing cognitive impairment was lower in treated hypertensive patients (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.38 to 0.83; p =.004). Neither the number of antihypertensive classes (the decline in MMSE score in those receiving one class was 0.9 ± 1.1 vs 0.7 ± 1.2 in those receiving two classes and 0.6 ± 2.0 in those receiving three classes, p =.13) nor the exposure duration (rate of decline per each day of exposure = 0.0002 ± 0.0006 points [p =.7] on MMSE, 0.0002 ± 0.0002 points [p =.3] on CDT) had an effect on the rate of cognitive decline or development of cognitive impairment. Compared with those patients receiving one class and those receiving two classes, the OR of dementia was 0.86 (95% CI, 0.59 to 1.26; p =.437). In those patients receiving three or more classes, the OR was 1.31 (95% CI, 0.78 to 2.19; p =.312).



View larger version (20K):
[in this window]
[in a new window]
  		Figure 1. Mini-Mental Status Examination (MMSE) scores versus time in different groups. (A) Patients taking versus not taking antihypertensive medications. (B) Patients taking antihypertensive medications versus those not taking antihypertensive medications versus patients without hypertension. (C) Patients without dementia who were taking antihypertensive medications versus those without dementia not taking antihypertensive medications. (D) Patients with Alzheimer's disease (AD) who were taking antihypertensive medications versus those with AD not taking antihypertensive medications. Probability values obtained from the mixed models compare the rate of decline of MMSE scores using the longitudinal sample

 
Patients receiving ARB demonstrated a trend for improved MMSE scores (p =.016) and CDT scores (p =.03) compared with those patients who were not receiving ARB. Persons receiving diuretics (p =.007), ACE (p =.016), and BB (p =.014) had a lower rate of decline in MMSE scores compared with those patients who were not receiving diuretics, ACE, or BB, respectively. Patients who were receiving clonidine had a higher rate of decline (p <.001) compared with those who were not receiving clonidine (Table 3). Patients receiving diuretics (OR, 0.51; 95% CI, 0.30 to 0.86; p =.01), ACE (OR, 0.62; 95% CI, 0.44 to 0.88; p =.008), and ARB (OR, 0.40; 95% CI, 0.17 to 0.93; p =.034) were at lower risk for the development of cognitive impairment. We found no difference in the risk for development of cognitive impairment in those receiving BB (OR, 0.91; 95% CI, 0.51 to 1.63; p =.75), dihydropyridine calcium channel blockers (OR, 1.41; 95% CI, 0.98 to 2.01; p =.061), non-dihydropyridine calcium channel blockers (OR, 0.34; 95% CI, 0.11 to 1.07; p =.34), alpha-blockers (OR, 1.05; 95% CI, 0.30 to 3.64; p =.94), and clonidine (OR, 1.86; 95% CI, 0.55 to 6.28; p =.31).


View this table:
[in this window]
[in a new window]
  		Table 3. Mean Exposure, Change in MMSE and CDT Scores Decline by Class of Antihypertensive Medications in the Longitudinal Analysis.

 

   DISCUSSION
Top
 Abstract
 Methods
 Results
 Discussion
References
 
We found that the use of antihypertensive medications may be associated with a decreased risk for the development of cognitive impairment in a population of older adults followed at a primary care practice. This effect is independent of baseline cognitive function and blood pressure level, and it is present in persons with a clinical diagnosis of dementia or AD. In addition, this study suggests that diuretics, ACE, ARB, and BB are the antihypertensive classes that may be associated with this lower risk. Furthermore, our data suggest that the use of ARB may even lead to improved cognitive function.

Recently, Murray and colleagues (19) reported that the use of antihypertensive medications in an African American elderly population was associated with a risk reduction of 38% in cognitive impairment, a reduction similar to our result in the current study. Investigators noted similar trends in the Kungsholmen project (OR, 0.6; 95% CI, 0.3 to 1.2) and in the Rotterdam study (OR, 0.76; 95% CI, 0.52 to 1.12); however, the risk reduction was not statistically significant (30,31). Our study, however, adds the evidence that this association is present in persons with a preexisting dementia illness, including AD, and in persons with intact cognitive function. We found this association in the longitudinal but not the cross-sectional analysis at baseline, which suggests that the association is not related to patient selection for antihypertensive treatment. Also at baseline, we found no difference in cognitive scores between persons who were receiving or not receiving antihypertensive medications. We also adjusted all models for baseline cognitive function to minimize the effect of this potential selection bias.

Our study suggests that patients using diuretics and BB have a lower rate of decline in cognitive testing scores. Previous reports about the effect of diuretics and BB on cognition have been conflicting (20,32). For example in the Systolic Hypertension in the Elderly Program, in which participants were treated with a diuretic or a BB, the investigators found no difference between treated and untreated participants on various cognitive measures (20,32). In contrast, in 1999 Guo and colleagues (30) reported that dementia was less likely to develop in participants using diuretics. The difference in these studies is likely related to the study population and the cognitive tests used. Although our sample size for the longitudinal analysis was relatively small, the current study supports the evidence that the use of diuretics or BB is associated with a lower rate of cognitive decline. Furthermore, diuretic use was associated with a lower incidence of cognitive impairment.

Animal models and observational studies have suggested a role of the renin-angiotensin system in cognition and dementia (33–35). For example, patients with AD have an increased frequency of angiotensin-converting enzyme I allele (36) and an increased density of angiotensin-converting enzyme in the temporal cortex (37). The number of studies assessing the effect of ACE on cognition is small (38). Our study suggests that ACE can provide protection against cognitive decline independent of cerebrovascular disease. Evidence about the effect of ARB on cognition is also scarce (34). A recent clinical trial showed that the use of an ARB agent was associated with increased MMSE scores (p <.001) compared with a thiazide diuretic (39). Our study suggests that the use of ARB is associated with improved cognitive function. If this finding is confirmed on a larger scale, ARB could potentially provide an additional means of therapy for persons with existing cognitive impairment. We found no association between calcium channel blockers or alpha-blockers and cognitive impairment. Previous clinical trials have found a protective effect of a dihydropyridine calcium channel blocker, which is not currently used in the United States, against cognitive impairment (22).

We have found that persons using clonidine show a greater decline in their cognitive function. This finding, although in agreement with previous reports (17,40), should be interpreted cautiously because of the small number of patients in our sample who were taking clonidine.

A limitation of our study was our inability to confirm drug exposure. We reviewed medications listed on patients' charts to assess current antihypertensive exposure and confirmed the medical record lists with providers' documentation and written prescriptions to increase reliability. In addition, we could not assess past exposure to antihypertensive medications.

Another limitation of our study is that serial cognitive testing may occur more frequently in those patients demonstrating cognitive impairment. However, this would be true for both those receiving and those not receiving antihypertensive medications and thus would not affect our comparisons. Furthermore, this was an observational study and exposure to antihypertensive medications was not randomized. It is possible that persons who show cognitive impairment are less likely to be prescribed antihypertensive medications in the first place. However, this would have a minimal effect on our findings because baseline cognitive function was similar between those patients receiving and those not receiving antihypertensive medications.

The smaller sample size of the longitudinal group represents another limitation. The characteristics of the longitudinal sample were similar to those of the cross-sectional sample, suggesting that this limitation would have a small effect on our results. Because of the relatively small sample size, the results of the multiple comparisons (Figure 1B) among nonhypertensive patients, hypertensive patients receiving medications, and hypertensive patients not receiving medications need to be interpreted cautiously. The results of our longitudinal analysis need to be confirmed by randomized clinical trials.

Conclusions
Until a clinical trial testing the effect of the different classes of antihypertensive medications on cognition in older adults is conducted, most of our evidence will depend on observational studies. In this study, we found that in older patients, including those with dementia and AD, and those using diuretics, ACE, BB, and ARB may provide protection against progressive cognitive decline. In addition, this study suggests that use of an ARB may even be associated with cognitive improvement. Studies to confirm our findings are urgently needed. If confirmed, our finding will have considerable economic and public health effects.


   Footnotes
 
Decision Editor: John E. Morley, MB, BCh

Received July 21, 2003

Accepted September 17, 2003


   References
Top
 Abstract
 Methods
 Results
 Discussion
 References
 

  1. The Alzheimer's Disease and Related Disorders Association. Statistics About Alzheimer's Disease, 2002 7/02. Report LIB620Z. Chicago, IL: ADRDA; 2002.
  2. Birkenhager WH, Forette F, Seux ML, Wang JG, Staessen JA. Blood pressure, cognitive functions, and prevention of dementias in older patients with hypertension. Arch Intern Med. 2001;161:152-156.[Abstract/Free Full Text]
  3. Launer LJ, Masaki K, Petrovitch H, Foley D, Havlik RJ. The association between midlife blood pressure levels and late-life cognitive function. The Honolulu-Asia Aging Study. JAMA. 1995;274:1846-1851.[Abstract/Free Full Text]
  4. Kivipelto M, Helkala EL, Laakso MP, et al. Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann Intern Med. 2002;137:149-155.[Abstract/Free Full Text]
  5. Skoog I, Lernfelt B, Landahl S, et al. 15-year longitudinal study of blood pressure and dementia. Lancet. 1996;347:1141-1145.[Medline]
  6. Kilander L, Nyman H, Boberg M, Hansson L, Lithell H. Hypertension is related to cognitive impairment: a 20-year follow-up of 999 men. Hypertension. 1998;31:780-786.[Abstract/Free Full Text]
  7. Farmer ME, Kittner SJ, Abbott RD, Wolz MM, Wolf PA, White LR. Longitudinally measured blood pressure, antihypertensive medication use, and cognitive performance: the Framingham Study. J Clin Epidemiol. 1990;43:475-480.[Medline]
  8. Tzourio C, Dufouil C, Ducimetiere P, Alperovitch A. Cognitive decline in individuals with high blood pressure: a longitudinal study in the elderly. EVA Study Group. Epidemiology of Vascular Aging. Neurology. 1999;53:1948-1952.[Abstract/Free Full Text]
  9. Desmond DW, Tatemichi TK, Paik M, Stern Y. Risk factors for cerebrovascular disease as correlates of cognitive function in a stroke-free cohort. Arch Neurol. 1993;50:162-166.[Abstract/Free Full Text]
  10. Kivipelto M, Helkala EL, Laakso MP, et al. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ. 2001;322:1447-1451.[Abstract/Free Full Text]
  11. Farmer ME, White LR, Abbott RD, et al. Blood pressure and cognitive performance. The Framingham Study. Am J Epidemiol. 1987;126:1103-1114.[Abstract/Free Full Text]
  12. Scherr PA, Hebert LE, Smith LA, Evans DA. Relation of blood pressure to cognitive function in the elderly. Am J Epidemiol. 1991;134:1303-1315.[Abstract/Free Full Text]
  13. van Boxtel MP, Gaillard C, Houx PJ, Buntinx F, de Leeuw PW, Jolles J. Can the blood pressure predict cognitive task performance in a healthy population sample? J Hypertens. 1997;15:1069-1076.[Medline]
  14. Seux ML, Thijs L, Forette F, et al. Correlates of cognitive status of old patients with isolated systolic hypertension: the Syst-Eur Vascular Dementia Project. J Hypertens. 1998;16:963-969.[Medline]
  15. Wallace RB, Lemke JH, Morris MC, Goodenberger M, Kohout F, Hinrichs JV. Relationship of free-recall memory to hypertension in the elderly. The Iowa 65+ Rural Health Study. J Chronic Dis. 1985;38:475-481.[Medline]
  16. Cacciatore F, Abete P, Ferrara N, et al. The role of blood pressure in cognitive impairment in an elderly population. Osservatorio Geriatrico Campano Group. J Hypertens. 1997;15:135-142.[Medline]
  17. Larson EB, Kukull WA, Buchner D, Reifler BV. Adverse drug reactions associated with global cognitive impairment in elderly persons. Ann Intern Med. 1987;107:169-173.
  18. Richards SS, Emsley CL, Roberts J, et al. The association between vascular risk factor-mediating medications and cognition and dementia diagnosis in a community-based sample of African-Americans. J Am Geriatr Soc. 2000;48:1035-1041.[Medline]
  19. Murray MD, Lane KA, Gao S, et al. Preservation of cognitive function with antihypertensive medications: a longitudinal analysis of a community-based sample of African Americans. Arch Intern Med. 2002;162:2090-2096.[Abstract/Free Full Text]
  20. Applegate WB, Pressel S, Wittes J, et al. Impact of the treatment of isolated systolic hypertension on behavioral variables. Results from the systolic hypertension in the elderly program. Arch Intern Med. 1994;154:2154-2160.[Abstract/Free Full Text]
  21. Forette F, Seux ML, Staessen JA, et al. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) Study. Arch Intern Med. 2002;162:2046-2052.[Abstract/Free Full Text]
  22. Forette F, Seux ML, Staessen JA, et al. Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Lancet. 1998;352:1347-1351.[Medline]
  23. Folstein MF, Folstein SE, McHugh PR. ‘Mini-Mental State.’ A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189-198.[Medline]
  24. Sunderland T, Hill JL, Mellow AM, et al. Clock drawing in Alzheimer's disease. A novel measure of dementia severity. J Am Geriatr Soc. 1989;37:725-729.[Medline]
  25. Anthony JC, LeResche L, Niaz U, von Korff MR, Folstein MF. Limits of the ‘Mini-Mental State’ as a screening test for dementia and delirium among hospital patients. Psychol Med. 1982;12:397-408.[Medline]
  26. Littell RC. SAS System for Mixed Models. Cary, NC: SAS Institute; 1996.
  27. Littell RC, Henry PR, Ammerman CB. Statistical analysis of repeated measures data using SAS procedures. J Anim Sci. 1998;76:1216-1231.[Abstract/Free Full Text]
  28. Wolfinger RD. An example of using mixed models and PROC MIXED for longitudinal data. J Biopharm Stat. 1997;7:481-500.[Medline]
  29. SAS P. SAS/STAT User's Guide, 8th ed. Cary, NC: SAS Publishing; 2000.
  30. Guo Z, Fratiglioni L, Zhu L, Fastbom J, Winblad B, Viitanen M. Occurrence and progression of dementia in a community population aged 75 years and older: relationship of antihypertensive medication use. Arch Neurol. 1999;56:991-996.[Abstract/Free Full Text]
  31. in't Veld BA, Ruitenberg A, Hofman A, Stricker BH, Breteler MM. Antihypertensive drugs and incidence of dementia: the Rotterdam Study. Neurobiol Aging. 2001;22:407-412.[Medline]
  32. Guo Z, Fratiglioni L, Viitanen M, et al. Apolipoprotein E genotypes and the incidence of Alzheimer's disease among persons aged 75 years and older: variation by use of antihypertensive medication? Am J Epidemiol. 2001;153:225-231.[Abstract/Free Full Text]
  33. Culman J, Blume A, Gohlke P, Unger T. The renin-angiotensin system in the brain: possible therapeutic implications for AT(1)-receptor blockers. J Hum Hypertens. 2002;16:(Suppl 3): S64-S70.
  34. Gard PR. The role of angiotensin II in cognition and behaviour. Eur J Pharmacol. 2002;438:(1-2): 1-14.[Medline]
  35. Braszko JJ. AT(2) but not AT(1) receptor antagonism abolishes angiotensin II increase of the acquisition of conditioned avoidance responses in rats. Behav Brain Res. 2002;131:79-86.[Medline]
  36. Cheng CY, Hong CJ, Liu HC, Liu TY, Tsai SJ. Study of the association between Alzheimer's disease and angiotensin-converting enzyme gene polymorphism using DNA from lymphocytes. Eur Neurol. 2002;47:26-29.[Medline]
  37. Barnes NM, Cheng CH, Costall B, Naylor RJ, Williams TJ, Wischik CM. Angiotensin converting enzyme density is increased in temporal cortex from patients with Alzheimer's disease. Eur J Pharmacol. 1991;200:289-292.[Medline]
  38. Sudilovsky A, Cutler NR, Sramek JJ, et al. A pilot clinical trial of the angiotensin-converting enzyme inhibitor ceranapril in Alzheimer disease. Alzheimer Dis Assoc Disord. 1993;7:105-111.[Medline]
  39. Tedesco MA, Ratti G, Mennella S, et al. Comparison of losartan and hydrochlorothiazide on cognitive function and quality of life in hypertensive patients. Am J Hypertens. 1999;12:(11 Pt 1): 1130-1134.[Medline]
  40. Solomon S, Hotchkiss E, Saravay SM, Bayer C, Ramsey P, Blum RS. Impairment of memory function by antihypertensive medication. Arch Gen Psychiatry. 1983;40:1109-1112.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 AM J ALZHEIMERS DIS OTHER DEMENHome page
I. M. Hajjar, M. Keown, P. Lewis, and A. Almor
Angiotensin Converting Enzyme Inhibitors and Cognitive and Functional Decline in Patients with Alzheimer's Disease: An Observational Study
American Journal of Alzheimer's Disease and Other Dementias, March 1, 2008; 23(1): 77 - 83.
[Abstract] [PDF]

Home page
 AM J ALZHEIMERS DIS OTHER DEMENHome page
G. Gliebus and C. F. Lippa
The Influence of {beta}-Blockers on Delayed Memory Function in People With Cognitive Impairment
American Journal of Alzheimer's Disease and Other Dementias, February 1, 2007; 22(1): 57 - 61.
[Abstract] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Services
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
PubMed
Right arrow PubMed Citation

HOME ARCHIVE SEARCH TABLE OF CONTENTS