Summary Vascular dementia (VAD) is considered to be the second most common cause of dementia in Europe and the US. In Asia and many developing countries, it is more common than dementia of the Alzheimer’s type (DAT). VAD is the most preventable form of dementia associated with later life. The pathogenesis of VAD is multifactorial, and it represents a heterogeneous, not a homogeneous, clinical entity. Classification of VAD by pathogenesis is important for its prevention and treatment. Control of the risk factors for VAD reduces its incidence and stabilises or improves cognitive performance following stroke. Proper diagnostic evaluation of VAD requires: (i) a well defined quantitative assessment of the cognitive deficits present; (ii) assessment of risk factors for stroke; (iii) identification of cerebral vascular lesions by history, neurological examination and neuroimaging; (iv) exclusion of other causes of dementia;(?) establishment of a positive diagnosis of possible, probable or definite VAD versus DAT or mixed VAD/DAT; and (vi) identification of the temporal relationship between cognitive deficits and cerebral vascular lesions. VAD can be subdivided into 8 major types, as follows: (i) multi-infarct dementia secondary to large cerebral emboli [type 1]; (ii) strategically placed infarctions causing dementia [type 2]; (iii) multiple subcortical lacunar lesions secondary to atherosclerosis or degenerative arteriolar changes [type 3]; (iv) Binswanger’s disease (arteriosclerotic subcortical leukoencephalopathy) [type 4]; (v) mixtures of types 1, 2 and 3 [type 5]; (vi) haemorrhagic lesions causing dementia [type 6]; (vii) subcortical dementia secondary to hereditary factors (type 7); and (viii) mixtures of DAT and VAD (type 8). Treatment is dictated by the pathogenetic subtype of VAD that is present.

A prospective study of mean hemispheric cerebral blood flow (CBF) correlated with clinical status has now been completed for the past 54 months. Thirty-eight patients underwent superficial temporal to middle cerebral artery (STA-MCA) by-pass. They were compared with 22 patients with similar arteriographic lesions and clinical symptoms, treated medically throughout the same interval of time. Assignment to either treatment group was not randomized but depended solely on choice of patient or treating physician. Both groups were matched for age, clinical symptoms, angiographic abnormalities, and CBF values. All patients had proximal occlusion of one internal carotid artery or intracranial occlusive disease of the internal carotid or middle cerebral arteries. CBF measurements and clinical evaluations were repeated at regular intervals up to 54 months following surgery or institution of medical treatment. Mean follow up interval after STA-MCA by-pass was 28.7 months and for medical treatment was 29.7 months. Mean hemispheric CBF values for STA-MCA patients became significantly increased 2 weeks after operation. After that, CBF flow values decreased. At 24 months after surgery, flow values for surgically treated patients were significantly higher than among those treated medically, although there were no differences in flow values between the two groups at 3, 6,12, 36 and 48 months. Prospective clinical evaluations after STAMCA by-pass were as follows: 12 (32%) improved with cessation of TIAs and/or neurological improvement, 16 (42%) remained unchanged, 7 (18%) deteriorated (due to new or recurrent strokes) and 3 (8%) expired. Clinical results were the same for medical treatment: 6 (27%) improved, 10 (46%) unchanged, 4 (18%) deteriorated due to new or recurrent stroke, and 2 (9%) expired.

BACKGROUND AND PURPOSE:Vascular dementia (VAD) and dementia of the Alzheimer type (DAT) are malignant conditions of the elderly. More information is required to clarify expected lengths of survival, which condition is more lethal, and which risk factors may influence survival duration.METHODS:Cross-sectional and longitudinal designs were used. Survival interval was the period after study admission to death. From a population of 392 patients (of the 150 patients with VAD, mean age at entry was 68.3 years, of the 242 patients with DAT, mean age at entry was 73.0 years), there were 52 deaths, 26 patients with VAD and 26 patients with DAT. Pre-entry dementia symptoms were present for a mean of 3.1 years, with median follow-up of 3.6 years. Among 236 control subjects, there were 19 deaths. Entry age was 69.5 years, with median follow-up of 8.8 years. Influences of risk factors for stroke and body mass index on symptom duration, survival intervals, and cause of death were evaluated.RESULTS:Family history of neurodegenerative disorders, principally DAT, negatively influenced DAT survival. Body mass index declined with age and duration of pre-entry symptoms among men and women in all three groups. Before entry, for men, dementia symptoms were present for shorter periods compared with women. After entry, VAD and DAT patients had similar survival intervals. Causes of death were similarly distributed (78% of patients with VAD died from vascular causes, 56% of patients with DAT and 67% of the controls).CONCLUSION:VAD and DAT are malignant conditions negatively influencing survival times. Being a woman seems to play a protective role in symptom duration before diagnosis, but after diagnosis survival times of men and women were similar. We attribute equivalence of survival intervals among dementia groups to control of risk factors for cerebrovascular disease.

Migraine headaches usually decrease in frequency and severity and often cease during advancing age. Occasionally, migraineurs report late-life migrainous accompaniments, i.e., auras without headache, particularly when typical migraine attacks terminate or diminish following major or minor strokes, at which time the auras may become atypical. Clinical observations such as these suggest that degenerative cerebrovascular changes accompanying aging may modify the course of migraine headaches particularly those with aura. To test this hypothesis, we quantitated age-related changes in cerebral vasodilator capacitance by measuring local cerebral blood flow utilizing xenon contrast computed tomography (CT) scanning before and after oral administration of the pharmacological cerebral vasodilator, acetazolamide (Diamox). Measurements were compared among 27 normal volunteers without headache (aged 24-94 years; mean age 61.1 +/- 17.6) and 37 carefully categorized groups of migraine patients (aged 27-83 years; mean age 59.4 +/- 12.4). The normals comprised Group A. Migraineurs were divided into two subgroups: Group B consisted of 27 migraineurs with and without aura who continued to suffer from incapacitating and frequent headaches and Group C consisted of 10 migraineurs who no longer suffered from severe and frequent headaches, two of whom still complained of atypical auras of the "late-life migrainous accompaniments" type. Cerebral vasodilator capacitance significantly declined with advancing age among normals and the two groups of migraineurs, confirming the development of age-related cerebrovascular diseases. Global CBF increases after Diamox in Group B (with persistent and severe migraine), were significantly greater compared with normals without headache, and with Group C consisting of migraineurs whose headaches had decreased, subsided, or become replaced by late-life migrainous accompaniments (Group C). Results establish that cerebrovasodilator capacitance declines with advancing age, probably due to progressive cerebral atherosclerosis, since these declines were accentuated by risk factors for stroke, particularly TIAs or documented lacunar infarcts by CT. Progressive impairments of cerebral vasodilator capacitance among migraineurs were associated with: (i) reductions in frequency and severity of migrainous cephalalgia and (ii) appearance of late-life migrainous accompaniments.

The articles in this supplement to The American Journal of Medicine describe some of the important epidemiologic studies that have contributed to our understanding of the pathogenesis of Alzheimer's disease (AD) and the multiple factors that may modulate the expression of the disease. Genetic factors are clearly important in determining the risk of disease expression. As discussed in this supplement, several gene mutations have been identified that have in common an effect on the production of β-amyloid protein implicated in the pathogenesis of AD. However, these gene mutations account for only a very small proportion of the risk attributable to genetic factors. The magnitude of this risk can be estimated from concordance rates in identical twins. These rates vary among studies, reflecting primarily the age of the population studied. As one would anticipate, the older the population, the greater the concordance rate and the estimate of heritability.

The ability to utilize color information was investigated in 12 patients with mild to moderate probable Alzheimer's Disease (DAT) and in 12 age- and gender-matched control subjects. All subjects underwent testing of visual acuity and color vision before being tested with a cognitive task consisting of four conditions (no color, color as attention enhancer, color as valid cue, color as distracter). Although the groups did not differ in visual acuity or color vision, patients with DAT were less accurate than controls in all four conditions of the cognitive task. Both groups performed best with color as a valid cue and worst with color as distracter, but condition had a significantly stronger effect on patients than on controls. It is concluded that color is a potent stimulus attribute for patients with DAT.

Annals of the New York Academy of SciencesVolume 826, Issue 1 p. 483-489 Human Aging: Risk Factors For Cerebral Atrophy JOHN STIRLING MEYER, Corresponding Author JOHN STIRLING MEYER Cerebrovascular Research Laboratories, Veterans Affairs Medical Center, and Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USAa Address for correspondence: John Stirling Meyer, M.D., Director, Cerebrovascular Research Laboratories, Bldg. 110, Room 225, VAMC, 2002 Holcombe Boulevard—151A, Houston, Texas 77030. Phone, 713/794-7814; fax 713/794-7583.Search for more papers by this authorHISANAO AKIYAMA, HISANAO AKIYAMA Cerebrovascular Research Laboratories, Veterans Affairs Medical Center, and Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USASearch for more papers by this authorKARL F. MORTEL, KARL F. MORTEL Cerebrovascular Research Laboratories, Veterans Affairs Medical Center, and Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USASearch for more papers by this authorSHIZUKO KONNO, SHIZUKO KONNO Cerebrovascular Research Laboratories, Veterans Affairs Medical Center, and Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USASearch for more papers by this authorGAIANE M. MARGISHVILI, GAIANE M. MARGISHVILI Cerebrovascular Research Laboratories, Veterans Affairs Medical Center, and Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USASearch for more papers by this author JOHN STIRLING MEYER, Corresponding Author JOHN STIRLING MEYER Cerebrovascular Research Laboratories, Veterans Affairs Medical Center, and Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USAa Address for correspondence: John Stirling Meyer, M.D., Director, Cerebrovascular Research Laboratories, Bldg. 110, Room 225, VAMC, 2002 Holcombe Boulevard—151A, Houston, Texas 77030. Phone, 713/794-7814; fax 713/794-7583.Search for more papers by this authorHISANAO AKIYAMA, HISANAO AKIYAMA Cerebrovascular Research Laboratories, Veterans Affairs Medical Center, and Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USASearch for more papers by this authorKARL F. MORTEL, KARL F. MORTEL Cerebrovascular Research Laboratories, Veterans Affairs Medical Center, and Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USASearch for more papers by this authorSHIZUKO KONNO, SHIZUKO KONNO Cerebrovascular Research Laboratories, Veterans Affairs Medical Center, and Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USASearch for more papers by this authorGAIANE M. MARGISHVILI, GAIANE M. MARGISHVILI Cerebrovascular Research Laboratories, Veterans Affairs Medical Center, and Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USASearch for more papers by this author First published: 17 December 2006 https://doi.org/10.1111/j.1749-6632.1997.tb48509.xCitations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume826, Issue1Cerebrovascular Pathology in Alzheimer's DiseaseSeptember 1997Pages 483-489 RelatedInformation

Factors that accelerate rates of `normal' age-related cerebral atrophic and degenerative changes are important because they may predispose to cognitive declines. To determine characteristic patterns of normal aging, risk factors were correlated with serial neurological–neuropsychological examinations, CT measures of progressive cerebral atrophy, local tissue hypodensities, or perfusional declines. Both cross-sectional and longitudinal designs were utilized. Ninety-four cognitively and neurologically normal aging volunteers, 15 with a history of transient ischemic attacks (TIAs), were followed for mean intervals of 3.0±2.1 years. Results indicated that: (1) after age 60, cerebral atrophy, polio- and leuko-araiosis doubled and cerebral perfusion decreased, with marked individual variations; (2) risk factors independently accelerating cerebral atrophy and cortico-subcortical perfusional declines included TIAs, hypertension, smoking, hyperlipidemia, excessive alcohol consumption and male gender; (3) progressive leuko-araiosis correlated directly with cortical atrophy and cortical perfusional declines. We posit that: (1) cerebral atrophy and degenerative changes result from neuronal shrinkage and/or loss, which are accelerated by TIAs, hypertension, smoking, hyperlipidemia, excessive alcohol consumption and male gender; (2) accelerated cerebral atrophic and degenerative changes identified by neuroimaging should be considered as markers for depleted neuronal synaptic reserves, which predispose to cognitive declines. Interventions available for controlling some of these risk factors include control of TIAs, hypertension, and hyperlipidemia, as well as tobacco and alcohol withdrawal.

Cerebrovascular capacitance was tested by measuring local cerebral blood flow (LCBF) by xenon‐contrasted CT scanning before and after the oral administration of 14.3 mg/kg of acetazolamide among 45 subjects including 15 age‐matched controls without history of headache, 20 migraineurs with and without aura, 3 patients with cluster headache, and 7 patients with tension‐type headache. Percentage increases of LCBF were measured in 10 regions located throughout both hemispheres. Laterality indices for asymmetric LCBF increases were calculated. Local cerebral blood flow in cortical gray matter increased 5.9% in controls, 9.9% in patients with tension headaches, but 18.6% in both migraine and cluster headache patients; significantly greater LCBF increases than among controls or among patients with tension headaches (P<0.05). Increases in LCBF were significantly asymmetric among migraine and cluster patients and provoked typical unilateral vascular headaches which responded to sumatriptan. Maximal asymmetric LCBF increases also corresponded to the reported side of the induced headaches confirming their vascular pathogenesis. Patients with tension headaches and controls without history of headache did not develop head pain after acetazolamide.

Acta Neurologica ScandinavicaVolume 93, Issue s166 p. 148-149 Testing Xe/CT CBF cerebrovascular reserve for identifying migraine and differentiating Alzhemer's from vascular dementia John Stirling Meyer, John Stirling Meyer Cerebrovascular Research Laboratories, Department of Veterans Affairs Medical Center and Department of Neurology, Baylor College of Medicine, Houston, Texas, U.S.A.Search for more papers by this authorToshitaka Shirai, Toshitaka Shirai Cerebrovascular Research Laboratories, Department of Veterans Affairs Medical Center and Department of Neurology, Baylor College of Medicine, Houston, Texas, U.S.A.Search for more papers by this authorKarl F. Mortel, Karl F. Mortel Cerebrovascular Research Laboratories, Department of Veterans Affairs Medical Center and Department of Neurology, Baylor College of Medicine, Houston, Texas, U.S.A.Search for more papers by this authorKazuhiro Muramatsu, Kazuhiro Muramatsu Cerebrovascular Research Laboratories, Department of Veterans Affairs Medical Center and Department of Neurology, Baylor College of Medicine, Houston, Texas, U.S.A.Search for more papers by this authorHisanao Akiyama, Hisanao Akiyama Cerebrovascular Research Laboratories, Department of Veterans Affairs Medical Center and Department of Neurology, Baylor College of Medicine, Houston, Texas, U.S.A.Search for more papers by this author John Stirling Meyer, John Stirling Meyer Cerebrovascular Research Laboratories, Department of Veterans Affairs Medical Center and Department of Neurology, Baylor College of Medicine, Houston, Texas, U.S.A.Search for more papers by this authorToshitaka Shirai, Toshitaka Shirai Cerebrovascular Research Laboratories, Department of Veterans Affairs Medical Center and Department of Neurology, Baylor College of Medicine, Houston, Texas, U.S.A.Search for more papers by this authorKarl F. Mortel, Karl F. Mortel Cerebrovascular Research Laboratories, Department of Veterans Affairs Medical Center and Department of Neurology, Baylor College of Medicine, Houston, Texas, U.S.A.Search for more papers by this authorKazuhiro Muramatsu, Kazuhiro Muramatsu Cerebrovascular Research Laboratories, Department of Veterans Affairs Medical Center and Department of Neurology, Baylor College of Medicine, Houston, Texas, U.S.A.Search for more papers by this authorHisanao Akiyama, Hisanao Akiyama Cerebrovascular Research Laboratories, Department of Veterans Affairs Medical Center and Department of Neurology, Baylor College of Medicine, Houston, Texas, U.S.A.Search for more papers by this author First published: July 1996 https://doi.org/10.1111/j.1600-0404.1996.tb00583.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume93, Issues166July 1996Pages 148-149 RelatedInformation

A prospective case-control study was carried out to clarify associations of cerebr transient ischemic attacks (TIAs) and other stroke risk factors with progression and exa erbation of cardiovascular and cerebrovascular disorders; 243 neurologically norm controls and 123 TIA patients without prior history of stroke were followed up for mean interval of 4.4 years. Of TIA patients, 26 (21%) developed other events (excludi recurrent TIAs); 10 died of vascular causes (8.1%). Of controls, 44 (18%) develope events; 13 died of vascular causes (5.4%) and 3 from cancer. TIA patients were at 2 times greater risk than normal controls for stroke or death from vascular causes. The were predominantly male with significantly higher associations of risk factors for strok including hypertension, heart disease, diabetes mellitus, smoking, hyperlipidemia, alcoh consumption, and limited education. Controls developing vascular events compared wi controls who did not were older, more frequently male, and with greater incidences heart disease. TIA patients had lower rates of cerebral perfusion compared with contro that persisted throughout the study, with similar rates of decline related to aging amor both groups. Among TIA patients, stroke risk factors were more prevalent than amor controls. The longer their duration, the greater the incidence and the more rapid the rate of severe often fatal cardiovascular complications

This investigation was designed to clarify the chronic effects of cardiogenic emboli on cerebral perfusion and tissue densities within remaining noninfarcted brain. Local cerebral perfusion and tissue densities were measured by xenon-contrasted CT scanning and compared by cross-sectional designs among normal volunteers without heart disease (Group C, n = 44), normal volunteers with heart disease (Group N, n = 20), patients with heart disease and lacunar infarctions (Group L, n = 31) and patients with heart disease associated with cardiogenic cerebral embolism (Group E, n = 12). In Group E, remaining cortical and subcortical gray and white matter perfusion were reduced compared to Groups C and N (p = 0.01), but did not differ from Group L, who had similar profiles of risk factor for stroke. In Group E, perfusion was reduced within the thalamus ipsilateral to cortical infarctions (p < 0.05). There were no differences in remaining tissue densities between Groups E and L. It is concluded that reduced cerebral perfusion in noninfarcted regions among patients with cardiogenic emboli appears to be related to atherosclerosis of small cerebral vessels in a similar manner to patients with lacunes, but thalamo-cortical disconnections also contribute to cerebral hypoperfusion.