Cerebral embolism and Alzheimer's disease

Until recently, advanced age and genes were the only well established risk factors for Alzheimer's disease; hence it has not been possible to develop preventive strategies. Now, evidence of modifiable risk factors for Alzheimer's disease is increasing. On p 1119, Purandare and colleagues report an association between spontaneous cerebral emboli and dementia.¹ This case-control study provides evidence for the longlasting debate on the causes of Alzheimer's disease versus those of vascular dementia.

Purandare and colleagues used transcranial Doppler to detect spontaneous cerebral emboli, monitoring patients with Alzheimer's disease, patients with vascular dementia, and age and sex matched controls for an hour. These emboli were detected significantly more frequently in patients with dementia, and the frequency was similar in Alzheimer's disease and vascular dementia. This study thus joins a series of articles that have pointed out a necessary shift from the concept of two sharply separated types of dementia to a dementia spectrum, with pure Alzheimer's disease and pure vascular dementia at the extremes and a mixture of the two in various degrees as the rule rather than the exception.

One of the main characteristics of research on dementia has been the tendency to separate neurodegenerative and vascular pathology. However, the complexity of the relation between the two main subtypes is now obvious, as more and more research data show considerable overlap in risk factors, neuropathology, and clinical features. Several epidemiological studies have suggested an association between Alzheimer's disease and vascular risk factors including hypertension, hypercholesterolemia, obesity, diabetes mellitus, dietary fat intake, and physical inactivity.²,³ Moreover, carotid atherosclerosis⁴ and atrial fibrillation,⁵ two important sources of spontaneous cerebral emboli, have also been suggested as risk factors for dementia.

The coexistence of Alzheimer's-type changes and vascular neuropathological changes seems to be more common than would be expected by chance alone, and the two types of pathology have a synergistic effect, rather than simply additive effect, on the expression of dementia.⁶ In addition, studies comparing neuropathological findings at autopsy with clinical diagnoses of dementia indicate important discrepancies between clinical labels and pathological reality.⁷

The typical clinical picture of Alzheimer's disease includes a long preclinical phase with an insidious onset of dementia, while the classical description of cognitive decline due to vascular causes comprises a stepwise onset and course. While there are cases that match this classical representation, in many situations identifying a date of onset proves impossible.⁸ For example, large emboli may cause clinically visible strokes and lead to textbook cases of multi-infarct dementia, but small and clinically silent emboli occurring repeatedly over several months or years tend to cause slowly progressive brain damage and cognitive deficits.

The study by Purandare and colleagues is cross sectional and cannot draw a definite conclusion about cause and effect. The authors did not find any direct association between spontaneous cerebral emboli and cardiovascular risk factors (including carotid atherosclerosis and atrial fibrillation) in patients with dementia, implying that spontaneous cerebral emboli may be a universal phenomenon in dementia. But what mechanisms would lie behind an association between such emboli and dementia? It has to be kept in mind that factors such as blood pressure, serum cholesterol concentration, and body mass index often decline before dementia becomes obvious,³ perhaps as a consequence of the disease, which may attenuate their effect in a cross sectional design. Indeed, Purandare and colleagues mention that body mass index was lower in both groups of patients with dementia than in the control group.

Even if this study leaves the question of mechanisms unanswered, it emphasises one very important issue related to preventing and treating dementia. The classical view of dementia has strongly influenced therapeutic approaches, making it difficult to tailor treatments to patients' various needs. If the diagnosis is vascular dementia, treatment aimed at cognitive impairment is sometimes overlooked, and if the diagnosis is Alzheimer's disease, vascular factors may be overlooked. Artificially labelling patients with one single diagnosis is less helpful than trying to identify and treat all possible aetiopathogenic factors. Early and effective treatment of vascular risk factors may have positive effects not only for cardiac health but may also help in preventing or postponing the onset of dementia.