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(Stroke. 1997;28:1410-1417.)
© 1997 American Heart Association, Inc.

Articles

Interactive Effects of Age and Hypertension on Volumes of Brain Structures

Terri L. Strassburger, MD; Hing-Chung Lee, MD; Eileen M. Daly, BS; Joanna Szczepanik, MA; Jack S. Krasuski, MD; Marc J. Mentis, MD; Judith A. Salerno, MD; Charles DeCarli, MD; Mark B. Schapiro, MD; Gene E. Alexander, PhD

From the Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Md.

Correspondence to Gene E. Alexander, PhD, Laboratory of Neurosciences, Bldg 10, Rm 6C414, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892. E-mail gene{at}alw.nih.gov

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose Advanced age and hypertension have each been associated with changes in brain morphology and cognitive function. To investigate the interaction of age and hypertension with structural brain changes and neuropsychological performance in otherwise healthy patients with essential hypertension, we compared young-old (ages 56 to 69 years) and old-old (ages 70 to 84 years) hypertensive patients (n=27) with 20 age-matched normotensive healthy control subjects, using quantitative volumetric MRI and a battery of neuropsychological tests.

Methods Quantitative regions of interest and segmentation analyses were applied to MRI scans of brain to measure volumes of different brain structures and of cerebrospinal fluid (CSF). Severity of white matter hyperintensities (WMHs) was qualitatively rated in the MRI scans. A battery of neuropsychological tests was administered to each subject.

Results The combined hypertensive group (young-old and old-old) had smaller volumes of thalamic nuclei and larger volumes of CSF in the cerebellum and temporal lobes and showed poorer performance in memory and language tests than did the control subjects. Main effects for age were significant in multiple brain regions of interest. The old-old hypertensive patients and age-matched control subjects demonstrated volume reductions in brain structures and increases in ventricular and peripheral CSF volumes compared with the younger subjects. There was a significant groupxage-group interaction in temporal and occipital CSF, not related to WMH, with the old-old hypertensive patients having significantly larger CSF volumes in these regions than the young-old hypertensives and both healthy control groups.

Conclusions Hypertension exacerbates the morphological changes accompanying advanced age. Temporal and occipital regions appear most vulnerable to brain atrophy due to the interactive effects of age and hypertension.

Key Words: aging • hypertension • magnetic resonance imaging • neuropsychology

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
It is now well established that aging is associated with structural changes in the human brain. Studies using MRI have reported reductions in brain volumes and increases in CSF spaces indicative of greater brain atrophy with age.^{1 2 3 4} These structural changes can be seen to a significantly greater extent in individuals with essential hypertension.^{5 6} Hypertension at all ages also is associated with poorer performance in neuropsychological measures compared with normotensive groups.^{7 8 9 10} An agexblood-pressure interaction model has proposed that hypertension-related brain changes cause greater cognitive dysfunction with advancing age.^{10 11} Support for this model, however, has been variable, and no study has directly investigated brain changes due to the interaction of age and hypertension using quantitative volumetric MRI.

The mechanisms by which hypertension and age are related to structural brain changes and their association with cognitive function have not been fully elucidated. Many studies have focused on WMHs as contributing to the greater atrophy and poorer cognitive performance observed in older hypertensive individuals,^{12 13} since both age^{3 14 15 16} and hypertension^{13 14 15 16 17} have been associated with severity of WMH.

In the present study, volumes of brain structures and of CSF were evaluated using quantitative volumetric MRI in a well-treated sample of 27 hypertensive patients and 20 healthy age-matched control subjects. A battery of neuropsychological tests was used to assess cognitive function in both groups. We sought to further investigate the effects of age and hypertension on structural brain volumes and neuropsychological performance in a group of otherwise healthy patients with essential hypertension and normotensive control subjects. We hypothesized that hypertension-related structural brain changes and cognitive dysfunction would be exacerbated by advanced aging, with older hypertensive patients being more vulnerable to brain atrophy in areas that are susceptible to the combined effects of hypertension and aging. Furthermore, by controlling for severity of WMH, we investigated the relation of age and hypertension to structural brain changes independent of WMH effects.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Subjects
All participants were volunteers in an ongoing study of brain structure and function in hypertension at the Laboratory of Neurosciences of the National Institute on Aging (NIA). Admission criteria have been reported previously⁵ and are summarized here. Twenty-seven hypertensive patients (19 men, 8 women) were studied (mean±SD age, 67.4±7.3 years; range, 56 to 84 years). Mean duration of hypertension was 18.7 years (range, 2 to 39 years). Review of available medical records showed good control of hypertension. Apart from hypertension, patients had no medical, surgical, or psychiatric problems; no history of head injury; and no secondary causes of hypertension or disorders that might contribute to brain dysfunction as determined by history, physical examination, chest x-ray, ECG, brain MRI, and laboratory tests. No patient had a history of smoking. Eighteen patients had no evidence of end-organ damage; 9 patients (6 men, 3 women) demonstrated left ventricular hypertrophy by ECG criteria,^{18 19} and 2 of these patients (both men) also demonstrated proteinuria as measured by random urinalysis. Degree of hypertensive retinopathy (Keith-Wagener-Barker stages I to IV) in all patients was stage II or less. WMHs²⁰ or brain atrophy on MRI were not exclusionary criteria. This study was approved by the NIA Institutional Review Board. The subjects provided written informed consent after a full explanation of the purpose, procedures, and risks of the study. All procedures were in accordance with institutional guidelines.

A 2-week medication washout period was implemented to avoid any influence of antihypertensive therapy on cognitive performance.²¹ Three patients were taking no medication, 9 were taking a single-drug regimen (1 receiving an angiotensin-converting enzyme inhibitor, 2 receiving ß-blockers, 2 receiving a calcium channel blocker, and 4 receiving diuretics), 8 were taking two drugs (7 receiving a diuretic plus a ß-blocker, calcium channel blocker, centrally acting agent, or -adrenergic antagonist; 1 receiving a calcium channel blocker plus an -adrenergic antagonist), and 7 were taking three or more medications (a combination of the above-mentioned drugs). Blood pressure was measured daily for patients not taking medication. During the washout period, no patient had sustained blood pressure elevations of more than 180 mm Hg systolic or 110 mm Hg diastolic.

The control group consisted of 20 age-matched volunteers (11 men and 9 women; mean±SD age, 68.7±6.1 years; range, 56 to 86 years) with no medical, surgical, or psychiatric problems. Control subjects underwent the same screening procedures, neuropsychological tests, and MRI scans as did the hypertensive patients. There was no significant difference between the hypertensive and control groups in distributions of sex, education, and handedness (Table 1). The groups also did not differ in scores on the Mini-Mental State Examination²² (mean±SD: controls, 29.5±0.8; hypertensives, 29.4±0.8). Systolic and diastolic blood pressures were significantly higher in the hypertensive patients while off medications (Table 1).

View this table: [in this window] [in a new window]   Table 1. Subject Characteristics

To investigate the effects of hypertension on age, the hypertensive and control groups were divided into young-old (aged 56 to 69 years) and old-old (aged 70 to 84 years) age groups (Table 1). There was no significant difference among the four subgroups with respect to education, sex, and handedness. The young-old age group did not differ significantly in systolic and diastolic blood pressures from the old-old age group, and there was no significant groupxage-group interaction. The young-old and old-old hypertensive groups did not differ in duration of hypertension. Six of the 9 patients with left ventricular hypertrophy were in the young-old age group, and the 2 patients with proteinuria and left ventricular hypertrophy were in the old-old age group. The young-old and old-old hypertensive patients did not differ in the frequency of types of medications or the number of medications.

Magnetic Resonance Imaging
Brain MRI was performed on a 0.5-T MR scanner (Picker Instruments). Axial images were obtained from double-echo (TR, 2000 ms; TE, 20/80 ms) sequences of 18 contiguous 7-mm-thick slices taken from the foramen magnum to the vertex, parallel to the inferior orbitomeatal line.⁴ The proton density portion of the scan was used for subcortical nuclei measurements, and the T2-weighted images were used for ratings of WMH. Coronal spin-echo (TR, 2000 ms; TE, 20 ms) images were obtained from 30 to 34 contiguous 6-mm-thick slices obtained perpendicular to the inferior orbitomeatal line for measurement of cranium, cerebral hemispheres, lobes, cerebellum, and ventricular and peripheral CSF.²³

MRI data were transferred from the Picker system to a Sun Unix-based workstation (Sun Microsystems) for analysis by the Quanta image processing system (C.D., Bethesda, Md). As described previously,² the intracranial region was traced along the dura of the cranium. After filtering for correction of image artifacts, pixel-intensity histograms were obtained for each slice, and a threshold was determined for segmentation of CSF and brain matter.²⁴ ROIs were then traced, and CSF/brain volume ratios were determined by the segmentation threshold.

Right and left caudate, lenticular, and thalamic nuclei were traced on the axial images by a previously described method.⁴ The right and left cerebral ventricles and lobar brain regions were traced on the coronal images after they were filtered and segmented.² The frontal lobe was defined as all supratemporal structures anterior to the sylvian aqueduct. Temporal lobe volume was traced from the anterior pole of the temporal lobe to the sylvian aqueduct. The medial temporal lobe boundary was defined as a straight line from the angle of the medial temporal lobe, where it attaches to the temporal stem, to the midpoint of the operculum; the dura of the middle cranial fossa was then traced around each temporal lobe to complete the region. The parietal lobe was defined as brain matter posterior to the sylvian aqueduct, extending to the medial transverse fissure of striate cortex. Remaining caudal portions of the cerebral hemispheres were defined as occipital lobe.²³ A region including cerebellar brain was determined for brain matter and CSF values of the posterior fossa.

The volume of each region in cubic centimeters was calculated by multiplying the summed pixel cross-sectional area in square centimeters by slice thickness in centimeters. Volumes were expressed as percentages of the total traced intracranial volume to control for individual differences in head size. Volume of peripheral CSF was calculated as the total CSF, determined by segmentation, minus the ventricular CSF.⁴ Volumes of the hemispheres were computed by summation of the lobar volumes on each side. For all brain ROIs traced in this study, very high intrarater and interrater reliabilities have been previously demonstrated.²⁵

WMHs visible on T2-weighted MR images were rated qualitatively. A modification of the three-point rating scale, adopted by Fazekas et al,²⁰ was used to assess the extent of the white matter changes. PVHs were rated as 0, absence; 1, caps or pencil-thin lining; 2, smooth halo around the lateral ventricles; and 3, irregular PVH extending into the deep white matter. DWMH signals were rated as 0, absence; 1, punctate foci; 2, minimal confluence of foci; and 3, large confluent areas. WMH severity judged to be between the above anchor points received a 0.5-point rating, providing a six-point scale. High interrater reliability for this rating scale has been reported.⁵

Neuropsychological Tests
Each subject was administered a battery of neuropsychological tests. General intellectual function was assessed with the WAIS.²⁶ Measures of memory performance included the Selective Reminding Test (9-item, 8-trial)²⁷ and immediate and delayed recall for stories (logical memory) and figures (visual reproduction) from the Wechsler Memory Scale.²⁸ Visuospatial and visuoperceptual function was measured using the Extended Range Drawing Test,²⁹ the Benton Facial Recognition Test,³⁰ and the Block Patterns Subtest from the Hiskey-Nebraska Tests of Learning Aptitude.³¹ Measures of language function included Syntax Comprehension,²⁹ the Boston Naming Test,³² and the Controlled Word Association (FAS) Test.³³ Attention was assessed by the Trail Making Test (Trails A and B),³⁴ the Stroop Color and Word Test,³⁵ and the Block Tapping Span Test.³⁶ One hypertensive patient and one healthy volunteer did not receive the full battery of neuropsychological tests.

Statistical Analysis
Comparisons of demographic and clinical variables between hypertensive patients and healthy control subjects were performed using Student's t tests or ² tests where appropriate. Comparisons of demographic and clinical information between young-old and old-old hypertensives and healthy controls were performed using two-factor ANOVA or ² tests. Groupxage-group comparisons of neuropsychological measures were performed using two-factor ANOVA. To reduce the number of overall comparisons in the regional MRI analyses, we performed onmibus repeated measures ANOVAs with group and age group as between-group factors and hemisphere as a repeated measure factor for homologous ROIs. Analysis of individual regions was performed with a two-factor ANOVA (groupxage group). The pairwise simple effects of significant interactions were tested using Student's t tests. To statistically remove the effect of WMH from significant group, age group, and interaction effects, ANCOVA was subsequently performed after controlling for PVH and DWMH. Multiple regression analysis was performed to correlate clinical information with significant ROIs, after controlling for age, sex, and education. Comparisons of WMH between hypertensive patients and healthy control subjects were performed using the Mann-Whitney U test. Statistical significance is taken as P.05.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Volumes of cerebral structures normalized to total intracranial volume are presented in Table 2. Hypertensive patients and control subjects differed significantly in cerebellar CSF, temporal CSF, and thalamic nuclei, with the hypertensive group having smaller cerebral volumes and larger ventricles in these regions (Fig 1). Significant main effects for age were shown in more than half of the regions, with older subjects from both groups combined consistently demonstrating reductions in volumes of cerebral structures and increases in ventricular and peripheral CSF volumes compared with the younger subjects. There was a significant group (hypertensives versus controls)xage-group (young-old versus old-old) interaction in frontal brain, temporal CSF, and occipital CSF, indicating a group difference that is dependent on an age-group effect. Follow-up pairwise comparisons revealed that the old-old hypertensive patients had significantly smaller cerebral and larger CSF volumes in these regions compared with young-old hypertensives. The healthy control groups did not show this age difference in temporal and occipital CSF (Fig 2). The frontal brain of the young-old hypertensive subgroup was significantly larger than that of the healthy young-old control group (P<.05), but the old-old hypertensives did not differ from the old-old controls.

View this table: [in this window] [in a new window]   Table 2. MRI Volumes Normalized to Total Cranial Volume of Hypertensive Patients and Healthy Control Subjects

View larger version (17K): [in this window] [in a new window]   Figure 1. Group difference in cerebellar CSF (A) and thalamic nuclei (B) volumes expressed as percentage of total cranial volume between hypertensive patients (n=27) and healthy normotensive control subjects (n=20). *Hypertensives showed significantly larger cerebellar CSF and smaller thalamic nuclei volumes than controls; P<.01. The bars indicate mean values. Overall group differences were assessed using a groupxage-groupxhemisphere repeated measures ANOVA. Cerebellar CSF includes CSF volumes around brain regions of the posterior fossa.

View larger version (18K): [in this window] [in a new window]   Figure 2. Plot of mean occipital (A) and temporal (B) CSF volumes expressed as percentage of total cranial volume for young-old (n=17) and old-old (n=10) hypertensive patients and young-old (n=11) and old-old (n=9) healthy control subjects. Values are mean±SE of regional volumes in percent cubic centimeters of total cranial volume. *Old-old hypertensives showed significantly larger occipital and temporal CSF values than young-old hypertensives and young-old and old-old controls; P<.02. Overall group differences were assessed using repeated measures ANOVA, and pairwise simple effects were tested using Student's t tests.

There were significant groupxage-groupxhemisphere interactions in hemisphere, parietal, occipital, and peripheral CSF spaces (P<.04). Pairwise simple effects analyses revealed that the young-old hypertensive patients showed asymmetry in hemisphere CSF and occipital CSF (P<.02), with the left hemisphere having more CSF than the right. The old-old hypertensives, however, did not show an asymmetry in hemisphere CSF and occipital CSF or in parietal or peripheral CSF. The young-old healthy control subjects did not show asymmetry in any of the four CSF spaces, whereas the old-old healthy controls showed asymmetry in all four spaces (P<.01), with the left hemisphere showing more CSF than the right.

To ensure that our MRI findings were not due to normalization with total intracranial volume, we repeated the analyses using absolute MRI values. All group effects remained significant (P<.01), and all main effects for age remained significant (P<.05) except total cerebral brain, hemisphere brain, and temporal brain. All groupxage-group interactions remained significant except frontal brain, and all groupxage-groupxhemisphere interactions remained significant (P<.03).

The hypertensive group had significantly more severe DWMH ratings than the control group (1.28±0.82 compared with 0.63±0.58, mean±SD; z=-2.81, P<.005), but the groups did not differ significantly in PVH ratings (hypertensives, 1.41±0.90; controls, 1.00±0.87; z=-1.47, NS). To control for the influence of WMH on volume differences, we repeated the significant groupxage-groupxhemisphere analysis using ANCOVA with PVH and DWMH as covariates (Table 2). The group effects remained significant in the thalamic nuclei. The main effects for age remained significant in all regions. The groupxage-group interactions remained significant in frontal brain, temporal CSF, and occipital CSF. The groupxage-groupxhemisphere interactions remained significant in hemisphere, parietal, occipital, and peripheral CSF spaces.

Neuropsychological data are presented in Table 3. Hypertensive patients showed significantly poorer performance than control subjects in the WAIS Verbal IQ, WAIS Verbal Deviation Quotient (VDQ), WAIS Memory and Distractibility Quotient (MDQ), Wechsler Memory Scale immediate and delayed story recall, Selective Reminding Test, and Syntax Comprehension. A significant main effect for age was shown in the WAIS Perceptual Deviation Quotient (PDQ), Trails A, Extended Range Drawing Test, Hiskey-Nebraska Block Patterns, and Benton Facial Recognition Test, with the old-old subjects from both groups showing poorer performance than the young-old subjects. The old-old group showed better performance than the young-old group in the WAIS VDQ. A significant groupxage-group interaction was observed in Selective Reminding Test–long-term memory (SRT-LTM) failures. Simple effects revealed that the old-old hypertensives had significantly more long-term memory failures than young-old hypertensives and old-old healthy controls (P<.03). After the analysis using ANCOVA with PVH and DWMH as covariates was repeated (see Table 3), the group effects remained significant in the WAIS VDQ; the main effects for age remained significant in the WAIS VDQ, Trails A, Hiskey-Nebraska Block Patterns, and Benton Facial Recognition Test; and the groupxage-group interaction for SRT-LTM failures remained significant.

View this table: [in this window] [in a new window]   Table 3. Neuropsychological Performance of Hypertensive Patients and Healthy Control Subjects

There was no significant correlation between duration of hypertension, systolic and diastolic blood pressure, or neuropsychological measures and MRI regions that showed significant group effects or groupxage-group interactions in the hypertensives.

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
We confirmed previous structural brain imaging studies that demonstrated significantly greater atrophy in hypertensive patients compared with healthy age-matched control subjects.^{5 6 37} Our findings are also consistent with previous MRI studies of healthy aging by demonstrating greater atrophy in older than younger subjects,^{1 2 3 4 38} although our sample included hypertensive as well as healthy elderly subjects. Consistent with our hypothesis, we found that elderly hypertensive patients had significantly smaller cerebral structures and larger CSF volumes in several regions compared with older middle-aged hypertensive patients, whereas the healthy control subjects did not show this age effect.

To our knowledge, only one study has investigated the regional effects of hypertension on MRI brain volumes.⁵ This study from our laboratory demonstrated greater lateral ventricular volume and smaller left hemisphere brain volume in patients with well-treated hypertension of 10 years' duration without end-organ damage compared with healthy control subjects. Functional neuroimaging studies have shown reductions in regional cerebral metabolic rates for glucose and cerebral blood flow in subcortical nuclei, arterial border zones, and temporal and occipital cortices in hypertensive patients compared with healthy controls,^{39 40} more severe in untreated patients.^{41 42 43} Autopsy studies have demonstrated that the vascular hypertrophy seen in hypertension is especially prominent in medium- and small-sized vessels⁴⁴ and in the middle cerebral and basilar arteries.^{45 46}

Our study is consistent with previous functional neuroimaging studies showing hypertension effects in regions of the temporal cortex and subcortical nuclei. The reduction in thalamic nuclei volumes in our sample may represent an expression of the vascular changes, ischemia, or lacunar infarcts that commonly occur in the thalamus in hypertensive patients.^{47 48} Previous MRI studies have not routinely evaluated cerebellar volume. In our study, hypertensive patients showed greater CSF values for a region containing cerebellar brain. Our present findings differed from those reported by Salerno et al⁵ in patients with well-treated hypertension of 10 years' duration without end-organ damage, where only lateral ventricle enlargement and left hemisphere reduction in the hypertensive patients was observed. However, unlike the Salerno study,⁵ our sample included both men and women, did not exclude patients with evidence of end-organ damage, and was evaluated with measures of regional lobar volumes.

Structural MRI studies have revealed age-related reductions in volumes of the cerebral hemispheres^{2 4} and subcortical nuclei,⁴ as well as ventricular enlargement.^{1 3 4} The volume reductions are especially prominent in the frontal lobes.³⁸ Age-related reductions in brain volumes of the temporal lobes^{38 49 50} have also been observed, albeit not consistently.⁵¹ Our study combining hypertensives and controls showed age-related reductions in temporal lobe and subcortical nuclei volumes, as well as increases in frontal, temporal, parietal, and peripheral CSF spaces.

The strongest interaction of age and hypertension was in temporal and occipital regions, suggesting that these regions are especially vulnerable to the combined effects of age and hypertension. The interaction for frontal lobe volume may have reflected brain volume variability in our hypertensive sample, since the young-old hypertensives had larger frontal brain volumes than the young-old controls. It is possible that hypertension-related cerebrovascular hypertrophy⁴⁵ renders the brain susceptible to decreased CBF,^{42 43} abnormal CBF autoregulation,^{52 53} or abnormal blood pressure diurnal variation,⁵⁴ which preferentially affect regions also susceptible to the effects of aging through neuronal degeneration.⁵⁵ Our results suggest that regions supplied by arterial border zones of the middle and posterior cerebral arteries or the posterior circulation⁵⁶ are specifically vulnerable to age plus hypertension.^{46 57}

That left hemisphere atrophy was greater in several regions is consistent with previous reports of hemisphere asymmetry in aging.^{38 58} Our older healthy control subjects consistently showed asymmetry in hemisphere, parietal, occipital, and peripheral CSF volumes. The older hypertensive patients, however, demonstrated a lack of asymmetry in these regions. Thus, differences in hemisphere asymmetries may help to distinguish effects of hypertension from healthy aging. Further investigation is needed to determine whether the asymmetry difference is a consequence of hypertension or is related to other factors such as sex⁵⁸ or different medications.

Although WMHs appear to be in part a consequence of chronic cerebrovascular disease,⁵⁹ the significant interactions we observed were statistically independent of WMH. The significant group effects were influenced by WMHs, since only the thalamic nuclei remained significant after we controlled for WMH. However, the thalamic nuclei finding, as well as the significant groupxage-group interactions after we controlled for WMH, suggests that the presence of WMH or frank infarction does not account for all the structural brain changes observed with hypertension.

One third of our hypertensive young-old and old-old patients evidenced end-organ damage. End-organ damage, particularly in the two older patients who had both heart and kidney dysfunction, could have influenced the greater atrophy seen in the old-old group. When we repeated the analysis excluding these two subjects, the groupxage-group interactions remained significant even after controlling for WMH in temporal and occipital CSF volumes (P<.05) but was only a trend in frontal brain. Thus, the greater brain atrophy seen in the posterior brain regions in older hypertensive patients was not due to greater severity of end-organ damage. In addition, the frontal brain and occipital and temporal CSF effects remained significant after controlling for patient differences in the number of medications, using ANCOVA for comparisons between the young-old and old-old hypertensives.

Our hypertensive patients demonstrated significantly poorer performance in neuropsychological measures of verbal memory, verbal intellectual skills, and language comprehension compared with control subjects. The magnitudes of these group differences were relatively small. Other studies have demonstrated that hypertensive patients, whether taking antihypertensive medication or not, show poorer performance than normotensives in learning and memory tasks.^{8 9 12} Results have been mixed, however, concerning general intellectual function^{8 10} and language abilities.^{5 60} Consistent with previous studies, we found age-group differences in measures of visuospatial abilities, attention, and verbal comprehension.^{61 62} Finally, our older hypertensive patients showed significantly poorer performance in one measure of memory function (ie, SRT-LTM failures) compared with younger hypertensives and both healthy control groups. Furthermore, the group difference between the young and older hypertensive patients remained significant after controlling for number of hypertension medications. Although this supports the agexblood-pressure interaction model,^{10 11} other measures of memory function did not show this effect. Although memory performance was not correlated with any MRI volume, the poorer memory scores of hypertensive patients in our sample are consistent with temporal lobe MRI volume changes.

Our findings suggest that effective treatment of hypertension may be particularly important in the elderly, in whom a combination of advanced age and hypertension leads to greater brain atrophy. Our sample of hypertensive patients was well controlled, suggesting that more effective treatment is required in elderly hypertensives. Further research is needed to identify the underlying mechanisms involved in hypertension-related brain changes. With understanding of the factors that contribute to the morphological and functional abnormalities observed with hypertension, new treatments can be developed to specifically address the neurophysiological and cognitive changes associated with hypertension in the elderly.

	Selected Abbreviations and Acronyms

 

CSF = cerebrospinal fluid DWMH = deep white matter hyperintensity ECG = electrocardiogram PVH = periventricular hyperintensity ROI = region of interest TE = echo time TR = repetition time WAIS = Wechsler Adult Intelligence Scale WMH = white matter hyperintensity

	Acknowledgments

 
This work was supported by the Intramural Research Program of the National Institute on Aging. The authors thank Carol Kinslow, MSSW, CSW, and the Laboratory of Neurosciences nursing staff, headed by Kate Musallam, RN, MSN, for assistance with patient care and scheduling; Diane Teichberg, MS, for technical assistance with the MRI data; and Stanley I. Rapoport, MD, for helpful comments in the completion of this manuscript.

Received February 7, 1997; revision received April 18, 1997; accepted April 18, 1997.

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