Vascular Dementia Patterns and Protection by Antihypertensive Drugs
Vascular Dementia Patterns and Protection by Antihypertensive Drugs
Abstracts & Commentary
Sources: Looi JC, Sachdef PS. Differentiation of vascular dementia from AD on neuropsychological tests. Neurology 1999;53:670-678; Guo Z, et al. Occurrence and progression of dementia in a community population aged 75 years and older. Relationship of antihypertensive medication use. Arch Neurol 1999;56:991-996.
Looi and sachdef extracted a meta-analysis of 27 acceptable studies on vascular dementia (VaD) directed at the above title. These, and a larger number of anecdotal references, provide a number of clinical factors that may help to separate these diagnoses, although many experienced neurologists already recognize the difference in at least the advanced forms of either.
Fundamentally, Alzheimer’s disease (AD) undergoes an insidious but steadily progressive evolution, beginning mostly after 70 years of age. Often, the victim has one or more family members with similar memory losses. Short-term, episodic, verbal-event memory usually undergoes an early loss, followed by defects in semantic memory and eventually, long-term memory loss as well. Language degenerates, morsel by morsel, often developing into a progressive, general aphasia in later years. Motor dysfunction, if any, usually occurs late in the disease. Potential markers are the E3-4 alleles of the serum lipoproteins and an MRI brain scan that shows neither a large number of scattered white patches in the hemisphere nor consistently large ventricles. Hippocampal shrinkage may be defined by MRI in relatively late stages of the illness.
VaD occurs at roughly the same age or even younger than AD and usually develops one or more of four relatively consistent markers: similar VaD ancestral cases, but less consistently than with AD; a long history of even modest hypertension or other lipid-related arterial diseases; frontal lobe dysfunction in executive activities; and, early during the illness, a waxing and waning of memory as well as intentionality in behavior. As notedabove, MRI scanning usually defines multiple small and sometimes large demyelinated spots, mostly in the cerebrum, but consistent with focal ischemia, cerebral ventricular dilatation often occurs. Persons with vascular dementia tend to retain better language qualities than AD during the middle to late years of their problems. Many wander in and out of confusion, becoming incontinent and unsteady on their feet during the late stages.
Against the above background, Guo and colleagues describe a somewhat unexpected success in adding antihypertensive medication to the elderly dementia protection list.
Guo et al selected 1810 patients older than 74 years from the Stockholm area to conduct a dementia incidence study; 225 already had dementia, a prevalence of 12.4% at the time the study began. An additional 284 persons refused initial testing. This left 1307 without dementia for further testing after two years. Before the end of the two-year follow-up, 314 of the 1307 died, leaving 987 persons for detailed evaluation after 24 months. At the time of baseline assembly, subjects already taking diuretics with or without additional antihypertensive drugs had a higher score on the MMSE (P = 0.006) and a lower prevalence of dementia (P < 0.004). At the end of the two-year follow-up time another 199 of the baseline 987 had become demented (20%). Also, among a total of 314 deaths occurring before the full two years, 25 had become demented (8%). Overall, subjects taking antihypertension drugs had significantly less dementia than the remaining patients (P = 0.03).
Diuretics and other antihypertensive agents were taken by 484 persons at baseline. Despite the fact that they were a bit older and had more heart disease and stroke than persons not using antihypertensive drugs, the population receiving the drugs had significantly (P < 03) less dementia than did the remaining senescents.
In the 987 persons retested at two years (excluding deaths), subjects taking diuretics had an adjusted risk rate (RR) of 0.7 compared to the remaining population. Put another way, subjects not taking antihypertensive drugs declined into dementia at a rate of 17% per year. Persons taking the diuretics with or without other anti-hypertension agents had less than half that chance of becoming demented.
Comment by Fred Plum, md
Looi and Sachdef crystallize the major four clinical markers (exclusive of MRI film results) that best characterize the presence of cerebral-vascular dementia. As they emphasize, indicants of possible VaD should lead to suspicion of impaired clinical function but they lack firm, high probability. AD, on the other hand, by its absence of frontal lobe dysfunction and early characteristics of impaired short-term memory plus fractured language abilities, usually clinically characterizes itself. Identification of serum lipoprotein alleles E3 and/or E4 considerably increases the accuracy of diagnosing AD. As the following paragraph indicates, cerebral arterial sclerosis may have a lighter, treatable incidence than has previously been surmised.
Guo et al’s report expresses a major point, namely that even mild systemic hypertension apparently can independently cause dementia or accelerate the destruction resulting from several degenerative neurological illnesses. The message is clear: physicians treating patients of any age who develop blood pressure greater than 150/85-90 mmHg should consider prescribing permanent treatment with a diuretic or equivalent anti-hypertensive drug. AD, however, is not to be ignored as a subtle, additional factor to vascular dementia. First of all, the disease has no inexpensive laboratory tests that firmly identify the illness, and second, your editor knows of laboratory animal experiments that have found that cholinergic stimulants such as donepezil may improve the behavior of laboratory rodents following experimental obstruction of cerebral arteries. (Dr. Plum is Professor and Chairman of the Department of Neurology and Neuroscience at the Weill Medical College of Cornell University.)
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