Hisanao Akiyama

Risk factors accelerating cerebral degenerative changes, cognitive decline and dementia

Factors accelerating cerebral degenerative changes represent potentially modifiable risks for cognitive decline. Putative risk factors accelerating subtle cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT densitometry, perfusions and cognitive testing among neurologically and cognitively normative ageing volunteers.

Risk factors for cerebral degenerative changes and dementia.

It is concluded that the most important determinants for cerebral neurodegenerative changes and cognitive decline during aging are neuronal shrinkage and/or loss, which are accelerated by certain risk factors: e.g. TIAs, hypertension, heart disease, hyperlipidemia, smoking, heavy alcohol consumption, male gender, low educational status, family history of cerebrovascular disease and absence of estrogen replacement therapy among women. Some of these risk factors are remediable by therapeutic interventions, including prevention of TIAs and medications that control hypertension, heart disease, hyperlipidemia and estrogen replacement in postmenopausal women, as well as abstention from abuse of tobacco and alcohol. Cerebral neurodegenerative changes measured by neuroimaging appear to be premorbid markers for depleted neuronal and synaptic reserves which predispose to the onset of dementias of both VAD and DAT types. Normal subjects at risk for cognitive decline include those with TIAs, hypertension and heart disease since these risk factors measurably accelerate cerebral atrophy, ventricular enlargement, leukoaraiosis, and decline in cortical perfusion.

Age-related cerebrovascular disease alters the symptomatic course of migraine

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.

Acetazolamide Testing of Cerebral Vasodilator Capacity Provokes “Vascular” But Not Tension Headaches

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.

101 – Vascular Dementias

Publisher Summary This chapter describes vascular dementias (VAD). Vascular dementia can be subdivided into eight major types. VAD type 1, also termed multi-infarct dementia, is because of multiple, large cerebral infarctions arising from emboli of cardiogenic origin. Type 1 can also be caused by emboli from intramural atherosclerotic plaques located within the aortocephalic arterial tree. Vascular dementia type 2 consists of a single or several strategically placed infarcts involving, for example, the thalamus, frontal white matter, basal ganglia, or angular gyrus. VAD type 3 is caused by multiple, subcortical lacunar infarctions due to arteriosclerosis within the walls of the deep penetrating vessels. VAD type 4 is arteriosclerotic subcortical leukoencephalopathy of Binswangers type. VAD type 5 consists of admixtures of large and small infarcts giving rise to dementias having mixed cortical and subcortical features. VAD type 6 is due to large hemorrhagic lesions. The intracranial hematomas may be due to uncontrolled hypertension, small cryptic or large arteriovenous malformations, and ruptured intracranial aneurysms with or without vasospasm. VAD type 7 has similar clinical and neuroimaging features to type 3 except that in these rare cases the subcortical dementia with multiple lacunar infarctions of white matter and basal ganglia are caused by “cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.” VAD type 8 is a mixture of dementias of both the vascular and Alzheimers types occurring in the same individual. It is shown that cognitive impairments in VAD correlate directly with total volumes of impaired cerebral glucose metabolism. Longitudinal trials have shown that in nonhemorrhagic, ischemic VAD, control of risk factors, and antiplatelet therapy stabilized cognitive declines; cerebral infarctions, atrophy, and perfusion measured by computed tomography, which correlated with improved serial cognitive testing.

Testing Xe/CT CBF cerebrovascular reserve for identifying migraine and differentiating Alzhemer's from vascular dementia

Local Cerebral blood flow (LCBF) was measured by Xe/CT before and after 1 g of oral acetazolamide among 72 subjects (43 men, 29 women; age 66.32 15.8 years (mean2SD) which included neurologically normal volunteers (n= 14; 6 min, 8 women; 68.35 12.4 years), migraine patients (n= 11; 1 man, 10 women; 45.8213.7 years), DAT (n= 19; 13 men, 6 women; 76.257.5 years), IVD (n= 20; 17 men, 3 women; 67.1 ? 17.0 years), and cognitively intact stroke patients (n=8; 6 men, 2 women; 67.123.2 years). Plain and 14 serial xenon-enhanced CT scans were obtained at one minute intervals, at two levels to include all cortex, basal ganglia, and white matter during 26% stable xenon inhalation for 8 minutes. CT CBF measurements were repeated before and 50 minutes after acetazolamide. LCBF and local Hounsfield Unit densities (LHU) were calculated in cerebral cortex (frontal, temporal, parietal, and occipital), subcortical gray matter (caudate, putamen, and thalamus), and John Stirling Meyer, Toshitaka Shirai, Karl F. Mortel, Kazuhiro Muramatsu, Hisanao Akiyama

Management of Acute Stroke with Hyperosmolar Agents

This chapter discusses the treatment of acute stroke with hyperosmolar agents. Patients with the diagnosis of acute stroke require immediate and emergent medical treatment because cerebral edema begins within minutes after acute ischemic stroke and progresses during the first week, becoming maximal around the fourth day with high risk of fatal outcome. The majority of clinical trials, supplemented by abundant experimental studies utilizing animal models of acute stroke, report beneficial effects of hyperosmolar agents on cerebral edema due to acute cerebral infarction. Hyperosmolar agents commonly administered include: hypertonic glucose, sucrose, urea, mannitol, and glycerol. The clinical effectiveness of glycerol administration has been confirmed by a number of investigators utilizing controlled clinical trials and double-blind evaluations of clinical outcome among patients with acute cerebral infarction. Glycerol combined with dexamethasone also lowers intracranial pressure and decreases brain edema among patients with acute stroke as does the combination of glycerol plus low-molecular-weight dextran. Intravenous administration of mannitol has also been shown to reduce brain edema and intracranial pressure and to increase cerebral perfusion among patients with brain trauma, acute cerebral infarction, and hemorrhage. Mannitol, like glycerol, increases plasma levels of atrial natriuretic factor among patients with cerebral infarction and hemorrhage.