Cerebral blood flow in Alzheimer’s disease

Abstract

BackgroundAlzheimer’s disease (AD) dementia is a consequence of heterogeneous and complex interactions of age-related neurodegeneration and vascular-associated pathologies. Evidence has accumulated that there is increased atherosclerosis/arteriosclerosis of the intracranial arteries in AD and that this may be additive or synergistic with respect to the generation of hypoxia/ischemia and cognitive dysfunction. The effectiveness of pharmacologic therapies and lifestyle modification in reducing cardiovascular disease has prompted a reconsideration of the roles that cardiovascular disease and cerebrovascular function play in the pathogenesis of dementia.MethodsUsing two-dimensional phase-contrast magnetic resonance imaging, we quantified cerebral blood flow within the internal carotid, basilar, and middle cerebral arteries in a group of individuals with mild to moderate AD (n = 8) and compared the results with those from a group of age-matched nondemented control (NDC) subjects (n = 9). Clinical and psychometric testing was performed on all individuals, as well as obtaining their magnetic resonance imaging-based hippocampal volumes.ResultsOur experiments reveal that total cerebral blood flow was 20% lower in the AD group than in the NDC group, and that these values were directly correlated with pulse pressure and cognitive measures. The AD group had a significantly lower pulse pressure (mean AD 48, mean NDC 71; P = 0.0004). A significant group difference was also observed in their hippocampal volumes. Composite z-scores for clinical, psychometric, hippocampal volume, and hemodynamic data differed between the AD and NDC subjects, with values in the former being significantly lower (t = 12.00, df = 1, P = 0.001) than in the latter.ConclusionThese results indicate an association between brain hypoperfusion and the dementia of AD. Cardiovascular disease combined with brain hypoperfusion may participate in the pathogenesis/pathophysiology of neurodegenerative diseases. Future longitudinal and larger-scale confirmatory investigations measuring multidomain parameters are warranted.

Neurovascular unit impairment in early Alzheimer's disease measured with magnetic resonance imaging

“…The link between hypoperfusion and BBB leakage extent and strength complements the previous finding that hypoperfusion is correlated with cognitive decline and hippocampal volume decrease (Roher et al, 2012). Atrophy is one of the hallmarks of AD, but adding atrophy as a confounder did not change the (qualitative) results.…”

Dissecting the Contribution of Vascular Alterations and Aging to Alzheimer’s Disease

“…However, the relationship between reduced CBF and regional atrophy is not clear. In fact, no correlation between the two events was observed by Schuff and colleagues [71], while Roher and colleagues found that AD patients had a 20 % reduction in total CBF that was directly correlated with reduced pulse pressure, hippocampal volume, and cognitive measures, suggesting an association between brain hypoperfusion and dementia [72]. Similarly, a recent study reported significantly lower regional CBF bilaterally in both the frontal and temporal lobes in AD, whereas CBF was lower in left frontal and temporal white matter in vascular dementia patients [73].…”

Effect of metabolic abnormalities on cognitive performance and clinical symptoms in schizophrenia

“…While we cannot clearly explain the mechanisms linking metabolic abnormalities with cognitive dysfunctions, there are several hypothesis explaining this issue. Obesity and hypertension are wellestablished risk factors of atherosclerosis and this is one of the risk factors of age-related or neurodegenerative cognitive decline [19]. Antipsychotic-induced obesity is associated with leptin-resistance [20] and previous studies support a role of leptin in cognition [21].…”