CAN ANTIHYPERTENSIVES STAVE OFF AD?

Antihypertensive medication use may be associated with reduced incidence of Alzheimer’s disease, according to a report published March 13 in the online Archives of Neurology. However, Ara S. Khachaturian, PhD, and colleagues noted that "the effects with specific subclasses, primarily potassium-sparing diuretics, will require replication in new data."

The researchers found 355 persons with prevalent dementia during an initial multistage assessment in 5,092 persons 65 or older. Detailed drug inventory was obtained at baseline, and discrete time survival analyses were performed to examine the association between the use of antihypertensive medications at baseline with subsequent risk of Alzheimer’s disease. A second assessment of 3,308 remaining participants identified 185 persons with incident dementia, of whom 104 were diagnosed with Alzheimer’s disease. Among the 3,217 participants who provided medication information, 1,456 were using antihypertensive medications, including angiotensin-converting enzyme inhibitors, ß-blockers, calcium channel blockers, and diuretics.

The study results showed that users of antihypertensive medications were significantly older and less educated than nonusers and were also more likely to be women and to have a history of stroke, hypercholesterolemia, diabetes, or myocardial infarction. Use of any antihypertensive medication at baseline was associated with lower incidence of Alzheimer’s disease, and use of diuretics—specifically potassium-sparing diuretics—was associated with the greatest reduction in Alzheimer’s disease risk (more than a 70% reduction). While antihypertensive medication use was associated with an increased risk of death, use of potassium-sparing diuretics was not significantly associated with excess mortality.

Dr. Khachaturian and colleagues noted, "It is not clear why potassium-sparing diuretics in particular should be associated with a reduced risk of Alzheimer’s disease, but it is well known that both loop and thiazide diuretics reduce plasma potassium concentration while potassium-sparing diuretics ... typically lead to increased concentrations." In addition, they pointed out that low potassium concentrations are associated with oxidative stress, inflammation, platelet aggregation, and vasoconstriction, all possible contributors to the pathogenesis of Alzheimer’s disease.

"A subgroup analysis in which data on measured blood pressure were available showed that controlling for blood pressure did not appreciably change the findings," Dr. Khachaturian’s group stated. "Although the restricted sample size of the latter analysis limits definitive conclusions, the findings suggest that the protective effect of these antihypertensive medications may be independent of their ability to control blood pressure."

The researchers recommended further epidemiologic and basic sciences studies into the possible neuroprotective effects of potassium-sparing diuretics, dihydropyridine-type calcium channel blockers, and ß-blockers.

Khachaturian AS, Zandi PP, Lyketsos CG, et al. Antihypertensive medication use and incident Alzheimer disease: the Cache County Study. Arch Neurol. 2006 Mar 13; [Epub ahead of print].

NEUROBIOLOGIC LINK BETWEEN RISK TAKING AND LOWER PARKINSON’S DISEASE RATES?

There may be a neurobiologic link between low levels of sensation-seeking behavior—which may underlie the parkinsonian personality—and the hypothetical protective effect of smoking and coffee intake on Parkinson’s disease, as reported in the March Journal of Neurology, Neurosurgery, and Psychiatry.

Andrew H. Evans, FRACP, and colleagues examined 106 Parkinson’s disease patients matched by age and gender with 106 healthy controls. Participants completed a short version of Zuckerman’s Sensation Seeking Scale, the Geriatric Depression Scale, the Trait Anxiety Inventory, and food frequency questionnaires to determine current caffeine and alcohol intake. The researchers also collected data on past and current cigarette smoking.

Results showed that patients with Parkinson’s disease had lower sensation-seeking and higher depression and anxiety scores. They were less likely to have smoked, and they had lower caffeine and alcohol intake. In addition, the inverse association of Parkinson’s disease with sensation seeking also appeared to be independent of smoking and caffeine and alcohol intake. While low sensation seeking explained some of the apparent effect of caffeine and alcohol intake on Parkinson’s disease, the effect of smoking was weakened slightly when Zuckerman’s Sensation Seeking Scale was included in the regression model.

The researchers commented that brain dopamine systems might mediate particular behavioral and personality traits, such as a disinclination to take risks and reduced impulsive sensation-seeking traits, that sometimes precede the emergence of motor symptoms by decades. In Parkinson’s disease, impulsive sensation-seeking traits have been found to relate to dopaminergic function within cortical and striatal brain systems, they added.

That reduced sensation seeking appeared to predict Parkinson’s disease independently after adjustment for smoking, as well as for caffeine and alcohol intake, "raises the possibility that impulsive sensation-seeking traits may interact with smoking, and caffeine and alcohol intake behaviors and a biological vulnerability to Parkinson’s disease," Dr. Evans’ group stated, noting that low sensation seekers may also be more susceptible to environmental toxicants.

"Although these analyses support an effect of impulsive sensation-seeking traits on Parkinson’s disease risk, it does not necessarily prove a pattern of causation," noted the researchers, suggesting that reduced sensation-seeking scores "may simply reflect disease involvement of mesocorticolimbic dopamine systems leading to a suppression of linked behaviors in a protracted prodromal phase of Parkinson’s disease." However, the Zuckerman’s Sensation Seeking Scale scores related neither to the duration nor the severity of Parkinson’s disease in the study, stated Dr. Evans and colleagues.

Evans AH, Lawrence AD, Potts J, et al. Relationship between impulsive sensation seeking traits, smoking, alcohol and caffeine intake, and Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2006;77:317-321.

BRAIN TRAUMA SEVERITY A PREDICTOR OF PERSONALITY CHANGE IN YOUTH

Brain trauma injury severity and the presence of dorsal frontal damage in children and adolescents increase the occurrence of personality change, and preinjury adaptive function is a predictor of long-term personality change, as reported in the Winter 2006 Journal of Neuropsychiatry and Clinical Neurosciences.

Dr. Jeffrey E. Max, MBBCh, and colleagues consecutively recruited 177 participants ages 5 to 14 during their initial hospitalization following traumatic brain injury. The researchers assessed for injury and preinjury psychosocial variables six to 24 months after injury and followed the group prospectively for two years. Results showed that personality change occurred in 13% of the participants between six and 12 months after injury and in 12% during the second year after injury. Severity of injury consistently predicted personality change, and preinjury adaptive function predicted personality change only in the second year after injury.

In addition, after the researchers controlled for severity of injury and the presence of other brain lesions, lesions of the superior frontal gyrus were associated with personality change between six and 12 months following injury. Only lesions in the frontal lobe white matter were significantly related to personality change in the second year after injury. Furthermore, after childhood traumatic brain injury, neural correlates of personality change evolve between six and 12 months and 12 to 24 months after injury.

The new finding that preinjury adaptive function predicted personality change at the two-year assessment suggests that "even in this disorder, the behavioral manifestations of which are classically associated with the direct effect of brain damage, preinjury personal characteristics of the child may influence outcome," Dr. Max’s group reported.

The emerging relationship with frontal white matter lesions and the loss of the relationship with superior frontal gyrus lesions were additional changes in the pattern of predictors of personality change with the extended follow-up, the researchers pointed out. These findings "underscore the relevance of white matter damage to many adverse outcomes in childhood disorders of brain and behavior," noted Dr. Max and colleagues. "Personality change in the second postinjury year is related to severity of injury, diffuse frontal lobe white matter lesions and presumed resultant disrupted neuronal connectivity, in addition to preinjury adaptive function," the investigators concluded, pointing out the need for controlled pharmacological and psychosocial treatment trials for personality change following brain trauma injury.

Max JE, Levin HS, Schacher RJ, et al. Predictors of personality change due to traumatic brain injury in children and adolescents six to twenty-four months after injury. J Neuropsychiatry Clin Neurosci. 2006;18:21-32.

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