Arkadiusz Siennicki-Lantz

Cerebral Blood Flow in White Matter Is Correlated with Systolic Blood Pressure and EEG in Senile Dementia of the Alzheimer Type

The presence and functional significance of white matter lesions in the ageing brain and in dementia as well as their relation to blood pressure are often discussed. The aim of this study was to evaluate cerebral blood flow in white matter (WMCBF) and its relation to systemic blood pressure and multichannel EEG. WMCBF was measured in 24 elderly women with senile dementia of Alzheimer’s type (SDAT, median age 85.5, range 68–93) and 20 age-matched controls (median age 86.0, range 79–93) using 99mTc-HMPAO single photon emission CT. A significant low WMCBF could be observed in all analysed regions in SDAT subjects compared to controls, with the greatest decline in the posterior region (parietotemporo-occipital area). Correlations between quantified EEG from the posterior regions and WMCBF were seen. Systolic blood pressure was significantly lower in the SDAT group and was positively correlated with WMCBF in the posterior and anterior brain regions. Whether low systemic blood pressure is the result of cerebral dysfunction is unclear.

Cerebral perfusion in the elderly with nocturnal blood pressure fall

Cerebrovascular disease may be linked with vascular autoregulation in aging. The aim of this study was to examine relation between nocturnal blood pressure (BP) fall and cerebral blood flow (CBF) changes in elderly men. The prospective ‘Men born in 1914’ cohort study has been in progress since 1968 and included 809 subjects. After 14 years from the last follow up, 97 subjects reached the age of 82 and underwent CBF measurement and 24 h ambulatory blood pressure monitoring. Diastolic BP at night decreased in 84 subjects with median 12.7% and increased in 13 subjects with median 3.7%. Relative diastolic BP fall at night was negatively associated to CBF in temporal and infero‐parietal areas. Higher proportion of subjects with increasing systolic BP during the 14‐year period was observed in the subgroup with extreme nocturnal diastolic BP dip, irrespectively of BP values or prevalence of hypertension. Extreme nocturnal diastolic BP fall in a cohort of elderly men is correlated with focal changes in CBF. Further studies could explain if increasing BP in the elderly is a cause or result of pathological autoregulation, and if antihypertensive treatment increases nocturnal BP dip.

ORTHOSTATIC HYPOTENSION IN ALZHEIMER'S DISEASE : RESULT OR CAUSE OF BRAIN DYSFUNCTION?

In Alzheimer’s disease (AD), an association was found between autonomic dysfunction and frontal hypoperfusion in brain during orthostatic testing. To ascertain whether frontal hypoperfusion is dependent on longitudinal effects of hemodynamic disturbances, or contributes to them, we studied the relationship between the presence of orthostatic hypotension (OH) and resting cerebral blood flow (CBF) in late stages of AD. Twelve women with senile dementia of Alzheimer type (SDAT), and 15 non-demented women (mean age 82.6 years, SD 3.8 vs 81.8 years, SD 3.5) were examined with the orthostatic test. Four of 12 patients with SDAT, and 9 controls had OH (defined as systolic blood pressure fall ≥20 mmHg). CBF was determined under resting conditions using 600 Mbq 99mTc HMPAO single photon emission computerized tomography (SPECT), and quantified in cortical areas in relation to cerebellum. In patients with SDAT and OH, CBF was lower in frontal and parieto-frontal cortical areas than in SDAT patients without OH. The former group was younger and had a shorter dementia duration. No significant differences in CBF were observed between controls with vs without OH. No differences in SDAT patients with or without OH were observed in the Berger dementia scale or Katz’ ADL index. No difference in incidence of symptoms related to autonomic disturbances (diarrhea, obstipation, dysphagia, vertigo) was observed in either the SDAT or control group with regard to OH presence. Wq conclude that during the course of AD, OH can contribute to frontal brain changes and may exacerbate the disease. The further involvement of frontal dysfunction in aggravating blood pressure dysregulation in the elderly is discussed.

A Study of Regional Cerebral Blood Flow Using 99mTc-HMPAO-SPECT in Elderly Women with Senile Dementia of Alzheimer's Type

Thirteen women with senile dementia of Alzheimers type (SDAT) according to NINCDS-ADRDA and 21 age-matched control women, aged 75-96 years, were investigated with clinical examination, dementia rating scales and single photon emission computed tomography (SPECT) using 99mTc-hexamethylpropyleneamine oxime (HM-PAO) as a tracer of regional cortical blood flow. The aim was to study whether typical SPECT findings of SDAT were seen also in the very old having the disease for a longer period. Neuropsychological assessment with vocabulary and spatial tests was performed in the control women, and the results were divided in three subgroups, normal, borderline and abnormal. Regional perfusion values, expressed as a ratio between cortical and cerebellar HM-PAO uptake, were lower in frontal, temporoparietal and occipital cortices in SDAT patients than in controls. The SDAT patients had the lowest uptake in the posterior temporoparietal region (0.67 +/- 0.06) and the corresponding value in the controls (0.79 +/- 0.05) differed significantly, p < 0.0001. The interhemispheric ratio between right and left posterior temporoparietal regions was 0.99 +/- 0.05. Nine of the control women (43%) had pathological SPECT with hemispheric asymmetries in 6 cases and bilateral temporooccipital reductions in 3 women. The neuropsychological assessment matched the findings in 7 of these women. One of the control women was judged as pathological and 10 women as borderline according to the spatial and vocabulary tests. Four of the 10 women with borderline results had normal SPECT. The sensitivity of the assessment to detect abnormalities compared to SPECT was 78% if borderline and abnormal results were expressed as true-positive cases. The specificity was 67%.(ABSTRACT TRUNCATED AT 250 WORDS)

Smoking-Related Changes in Cerebral Perfusion in a Population of Elderly Men

Aim: Smoking and hypertension are known causes of stroke and dementia. This study was designed to test the longitudinal effect of lifestyle factors and hypertension on cerebral blood flow (CBF) in old age. Method: A study of an unselected population cohort of 703 men, born in 1914, has been in progress since 1968 and the last clinical examination occurred at age 69. CBF was examined in 129 survivors who reached 82 years, using SPECT. Results: At the age of 69, the study subjects consisted of 36 smokers, 37 nonsmokers and 56 former smokers who had quit. Fourteen years later, there were no differences in CBF among them. The cohort was stratified into 69 hypertensive and 60 normotensive men. CBF in normotensives was lowest in smokers and highest in nonsmokers. No CBF differences were observed in hypertensive men regarding smoking, but their CBF was as low as in normotensive smokers. Hypertensives had a higher BMI, and higher blood glucose and triglyceride levels, but lower alcohol consumption at 69 and a lower ankle-brachial pressure index at 82 years. Alcohol consumption was highest in normotensive smokers. Conclusion: Smoking and high alcohol consumption in normotensive men are correlated to low CBF in senescence. Low CBF in hypertensive men regardless of smoking may be due to a high vascular risk profile.

Low ambulatory blood pressure is associated with lower cognitive function in healthy elderly men.

IntroductionLow blood pressure (BP) has been found to be associated with cerebrovascular damage in the elderly. Studies of the relation of ambulatory BP to cognitive function in elderly persons aged 80 years or above is lacking, however. MethodsNinety-seven 81-year-old men from the population study ‘Men born in 1914’ underwent ambulatory BP monitoring and were given a cognitive test battery, 79 subjects completing all six tests. Low ambulatory systolic blood pressure (SBP) was defined as <130 mmHg and low ambulatory diastolic blood pressure (DBP) as <80 mmHg (corresponding in terms of office BP to approximately <140 and <90 mmHg, respectively). Odds ratios (OR) for lower cognitive function were calculated using a forward stepwise logistic regression model, controlling for confounding factors. ResultsSubjects with ambulatory SBP <130 mmHg had higher OR values for daytime (OR 2.6; P=0.037), nighttime (OR 3.6; P=0.032) and 24h (OR 2.6; P=0.038) BP measurements. A lower cognitive function was associated with lower nighttime SBP and DBP levels and lower 24-h mean SBP compared to subjects with higher cognitive function. OR values connected to low nocturnal SBP, had a tendency to be particularly high among subjects on anti-hypertensive drugs (OR 9.1; P=0.067, n.s.). ConclusionAmbulatory SBP levels <130 mmHg and lower nighttime SBP and DBP were associated with lower cognitive function in healthy elderly men. Further investigation is needed to ascertain the effects of the presently recommended treatment goal of <140 mmHg for office SBP also on elderly over 80 years of age.

Cerebral perfusion deficits in age-associated memory impairment. The role of tobacco smoking.

Background and aims: Several studies report a high prevalence of memory complaints in the elderly, non-demented population. Since the pathogenesis and diversity of memory impairment in healthy people is still an unresolved issue, we designed our study to ascertain the occurrence of brain abnormalities in Age-Associated Memory Impairment (AAMI) by measuring regional cerebral blood flow (rCBF). Methods: Fifty-three subjects were invited to the case-control study: 26 subjects who fulfilled the AAMI criteria, and 27 controls (age, mean±SD 65.8±7.3 vs 65.5±6.7). rCBF was determined using 99mTCECD SPECT by relative measurements made in the cortical and white matter regions and in the thalamus. Results: The AAMI group vs controls had restricted rCBF in the temporal lobe of the left hemisphere (median; 85.8 vs 87.8, p=0.04), in the thalamus (median; 87.3 vs 89.8, p=0.036) and the frontal white matter (median; right hemisphere 80.0 vs 84.1, p=0.01; left hemisphere 77.7 vs 81.6, p=0.04). AAMI subjects who previously smoked had lower rCBF values in the temporal, parietal, occipital and frontal lobes bilaterally, and poorer memory test results than ex-smoker controls. By contrast, rCBF did not differ between non-smoking AAMI subjects and controls. Conclusions: Compared to controls, AAMI subjects had restricted rCBF. A history of previous smoking could partly contribute to the rCBF differences between these groups. Further studies on failing memory and rCBF in representative cohorts of smoking and non-smoking populations are now needed.

Depressive symptoms, atherosclerotic burden and cerebral blood flow disturbances in a cohort of octogenarian men from a general population

BackgroundThe aim of this study was to examine in elderly men a relationship between depressive symptoms, peripheral vascular disease and cerebral blood flow (CBF).MethodsPopulation-based cohort study started with an examination of 809 men at age 55, followed by the first (age 68ys) and second follow up (age 82ys). 128 survivors were examined at age 82 with 99mTc-HMPAO-SPECT to estimate CBF, Zung-Self-Rating-Depression Scale (ZSDS), and Ankle-Brachial Index (ABI). Analysis was performed on men free from stroke and dementia which defined the final study population to 120 subjects.ResultsZSDS in the whole cohort ranged from 0.26 to 0.71 (reference 0.25-1.0). As the frequency of depressive symptoms was low, the case group (n = 31) was defined by ZSDS index above 75th percentile (≥0.48), comprising 9 subjects with mild depression (ZSDS 0.55-0.71) and 22 subjects at 88th percentile and above of the normal range (ZSDS index 0.48-0.54). Cases were more often current smokers at age 68 (44% vs. 24%; p = .02) and had lower systolic blood presure (SBP), lower social and physical activity, and suffered from fatigue, nausea, freezing and leg edema at age 82. Within the case group, ZSDS-index correlated negatively with CBF in subcortical area (r = -.42*), left and right thalamus (r = -.40*, r = -.46**), and right basal nuclei (r = -.35*). ZSDS-index correlated also with ABI at age 82 (right leg r = -.40*; left leg r = -.37*), and with Δ between ABI at age 82 and 68 (right r = -.36*; left r = -.46**). Despite decreasing SBP from age 68 to 82, adjusted multiple regression analysis showed in the case group that higher SBP determined CBF changes in the frontal and parietal areas, independently of ZSDS index, Δ ABI, and smoking.ConclusionIn this population-based cohort of octogenarian men free from stroke or dementia, a proportion of subjects with depressive symptoms was low. Still, men with borderline or mild depression scores had lower social and physical activity, persistent smoking habit, worse peripheral circulation in legs, and cerebral perfusion changes in basal nuclei, thalamus and subcortical white matter. Regional CBF decline could be partly mediated by higher SBP.

Lower cognitive performance in 81-year-old men with greater nocturnal blood pressure dipping.

Abnormal day-to-night blood pressure (BP) pattern have been found to be associated with cerebrovascular damage, yet studies of the elderly 80 years of age and above, for whom the risk pattern may be different due to ageing and age-associated diseases, are lacking. Ninety-seven 81-year-old men underwent ambulatory BP monitoring and were given six cognitive tests, 79 of the men completing the cognitive test battery. The odds ratio (OR) for performing one standard deviation below the mean on any cognitive test was calculated using a forward stepwise logistic regression model, confounding factors being controlled for. Groups defined in terms of day-to-night changes in BP were compared in this respect. Cognitive performance was lower (OR 3.6; P = 0.017) in the group usually described as dippers (10%–20% nocturnal drop in systolic BP [SBP]) as compared with nondippers (<10% drop). The tertile with the greatest SBP fall (10.6%–19.8%, a range considered as normal among middle aged) showed lowest cognitive performance (OR 4.7; P = 0.008) as compared with the middle tertile (5.1%–10.5% drop). The mean nocturnal fall in SBP was 7.4%, significantly greater in those with lower rather than higher cognitive performance. A nocturnal drop in SBP of ≥10% was associated with lower cognitive performance in these elderly men. The limits to normal dipping appear to be shifted in the direction of a lesser drop in the very elderly.

Carotid velocities determine cerebral blood flow deficits in elderly men with carotid stenosis <50%.

To examine if mild carotid stenosis correlates with silent vascular brain changes, we studied a prospective population-based cohort “Men born in 1914.” Data from followups at ages 68 and 81, have been used. Carotid ultrasound was performed at age 81, and cerebral blood flow (CBF) was measured with SPECT at age 82. Out of 123 stroke-free patients, carotid stenosis <50% was observed in 94% in the right and 89% in the left internal carotid arteries (ICAs). In these subjects, Peak Systolic Velocities in ICA correlated negatively with CBF in a majority of several brain areas, especially in mesial temporal area. Results were limited to normotensive until their seventies, who developed late-onset hypertension with a subsequent blood pressure, pulse pressure, and ankle-brachial index growth. Elderly with asymptomatic carotid stenosis <50% and peak systolic velocities in ICA 0.7–1.3 m/s, should be offered an intensified pharmacotherapy to prevent stroke or silent cerebrovascular events.