Many interesting papers and presentations given at the International Alzheimer's Disease Conference in Vienna, Austria in July offered information that is pertinent to practicing clinical neurologists. Below, I highlight a few of the studies* and their implications for clinicians.
Karin Yurko-Mauro, et al., presented the results of a paper entitled “The Effects of Docosa-Hexaenoic Acid On Physiological and Safety Parameters In Age Related Cognitive Decline.” DHA is the principle Omega 3 fatty acid in the brain. Four hundred eight-five subjects were enrolled in the randomized double blind placebo controlled multi-center study to determine whether 900mg of DHA produced any change from baseline in a visual spatial episodic memory test. The six-month study showed improved memory function in the DHAtreated patients as compared to placebo. The improvement shifted the treated patients to the normal cognitive function of a younger age group with an excellent safety profile. It is not quite clear from the study whether some of these patients might have had mild cognitive impairment of the amnestic type or just mild changes of normal aging. There was no evidence from a similar study that DHA was beneficial in Alzheimer's disease patients.
Synthesis: Currently there do not appear to be any specific vitamins or food supplements that are effective in slowing or preventing cognitive decline in the general population or in patients who are cognitively impaired. The use of 900mg of DHA appears to possibly have some benefit in the normal aging population in slowing cognitive decline. Further studies will likely be needed, but it seems that DHA is safe and without any side effects. It may be reasonable to recommend this to some of our elderly patients or perhaps to patients who have very mild cognitive decline. Another good source of DHA is salmon and tuna.
■ Norberg, A., et al., presented a paper entitled “PET Amyloid Imaging and Cognition in Patients with Alzheimer's Disease, Mild Cognitive Impairment and Healthy Controls,” which is a European multicenter study. In this study, there were 102 Alzheimer's patients with an MMSE of 23, 73 MCI patients with an MMSE of 27, and 52 controls with an MMSE of 29. The neuropsychological testing was done with special testing of verbal memory, attention, visual perception, and nonverbal memory. Age, gender, and education in all cases were similar. The studies showed that there was a statistical moderate increase in Pittsburg Compound B-binding in the frontal parietal area in the Alzheimer's cases compared to intermediate binding in the mild cognitively impaired patients. The binding in controls was very mild in five out of 52 normal subjects. There was an inverse correlation between the Pittsburg Compound B-binding in mild cognitive impairment and verbal and visual delayed memory scores. Forty-eight of the MCI patients were followed for one year; 15 converted clinically to Alzheimer's disease with evidence of increased PIB-binding. The study concluded that the Pittsburg Compound B PET imaging in six European Centers showed a significant difference in PIB-binding between mild cognitive impairment, Alzheimer's disease, and controls, and there was an inverse correlation between PIB-binding and cognition observed in the MCI and Alzheimer's disease cases.
Synthesis: This study showed that the amount of amyloid in the brain increased proportionally with worsening abnormalities on neuropsychological testing. This result is not surprising, since research has strongly suggested that more cognitive impairment in Alzheimer's disease should show more abnormal amyloid in the brain. This study further verifies this and will be very helpful in clinical practice once amyloid imaging is used in testing of cognitive impaired patients. This amyloid binding capability will be helpful in reducing the number of dementia cases that are diagnosed clinically with Alzheimer's disease but at autopsy are determined to have Lewy Body or frontal temporal dementia.
■ Foerster, and Stefan, et al., presented a paper entitled “Positive Effects of a Six-Month Stage Specific Cognitive Intervention Program on Brain Metabolism in Subjects with Amnestic Mild Cognitive Impairment and Mild Alzheimer's.” In the past it has been shown that cognitive intervention helps MCI and Alzheimer patients, but there has not been a study showing follow-up on brain PET scans to see if glucose metabolism changes. This study consisted of 21 patients with amnestic mild cognitive impairment, 15 with mild Alzheimer's, and controls. The cognitive intervention group had weekly seminars of specific cognitive intervention, while the other group received only a pencil and paper exercise for self-study. PET scans and neuropsychological baseline studies were done initially. At six-months, the controls showed a decreased decline in glucose in the parietal temporal, frontal, and posterior cingulate regions. The cognitive intervention group showed only discreet decreases in glucose metabolism in bilateral, prefrontal, left inferior temporal cortex, and less reduced glucose in the right parietal, cingulate, and frontal cortices regions. They showed that AMCI and Alzheimer's disease patients who participated in the six-month stage specific cognitive intervention as opposed to a self-study showed cognitive benefits by the neuropsychologist and delayed progression of reduced glucose metabolism in the brain and especially in regions affected by Alzheimer's disease. A longer study with larger population will likely need to be done.
Synthesis: This study adds further credence to the benefits of active cognitive rehabilitation in patients with mild cognitive impairment and Alzheimer's disease. This is important because cognitive intervention is under-utilized in patients with these disorders. Unlike medication, this is an active form of treatment and in my experience many patients are eager to take part in cognitive rehabilitation, and caregivers appear to be pleased with this intervention.
■ Another paper of interest was by Lincoln Dadina, B., et al., entitled “Driving Ability in People with Dementia.” They studied 118 dementia patients and 30 controls. They gave The Nottingham Neurodriving Assessment and a battery of neuropsychological testing. Of the 118 dementia patients, 27 were determined to be unsafe and 91 were safe. All the controls were safe and normal. The main problems with driving in dementia cases were: 1.) less likely to observe the rear of the car through the mirror, 2.) driving in the proper traffic lane, 3.) obedience to road signs. The problems that were determined on the road test of the dementia patients correlated strongly with a number of cognitive tests. These tests were: road sign recognition, mini mental test (MMSE), and a direct search test. Thirty percent of cases with dementia failed the driving test, and the failures directly correlated with poor performance on the cognitive tests. It appears that certain batteries of cognitive testing specifically predicted the ability of patients with dementia to drive safely.
Synthesis:We all know that some patients with Alzheimer's disease are able to drive reasonably safely, particularly in their own neighborhoods. This study is important in that there is a correlation between the outcome of a number of cognitive tests and the capabilities of many of our patients to drive. Many of our MCI and Alzheimer patients are sent for driver's evaluation. It would be useful for clinicians to do some of these tests in the office and determine ahead of time our patients' driving capabilities. Many of us in clinical practice use the driver's test to demonstrate to patients and their families that they should not be driving. Not uncommonly the driver's evaluation determines that the patient with dementia may drive, but only with supervision by the caregiver or only in small areas in the community. Many times caregivers are disappointed, because they were hoping that their loved ones would fail the test and the subject of driving and its conflicts would go away. An in-office test given by the neurologist, as suggested in this paper, might be a better prediction of which patients with Alzheimer's disease will pass or fail the drivers' test so we could counsel the caregivers accordingly.
■ Duran, E., et al., presented a paper entitled “The Effects of Anti-hypertensive Therapy in Cognitive Stability in Alzheimer's Disease.” They studied 290 Alzheimer's patients and followed them for three years. These patients averaged 78-yearsold, and 54 percent of these patients received antihypertensive therapy. The mini mental testing was done at year one. In year one the patients treated for hypertension had an MMSE score of 22 versus 20 for the non-hypertensive group. The MMSE score was 21 versus 19 at two years, and 19 versus 17 at three years. It appeared from the study that there were a high number of cognitively stable patients on antihypertensive therapy over time as shown by MMSE scores. In this study they used calcium channel blockers and ACE inhibitors.
Synthesis: This study suggested that patients with Alzheimer's disease who have hypertension and are treated appear to have more stability in cognitive function than patients who are not hyperten-sive and not on medication. Prior studies have suggested that the use of ACE inhibitors and some calcium channel blockers seems to have a possible effect on stability of brain function or slowing cognitive decline than other categories of anti-hypertensive agents. This could be the reason for the stability and less decline of treated hypertensive Alzheimer patients versus non-hypertensive Alzheimer's cases. This data, along with other studies, suggest that hypertension in cognitively impaired patients should be treated with antihypertensive medications in the ACE inhibitor or calcium channel blocker classes of medications.
■ Pecena, et al., had a paper entitled “The Association of Antipsychotic Drug Use and Mortality in the Very Old with Dementia, the Monzonio 80+ Study.” This is an ongoing study of all people 80- years-old or older in a province in Italy. At baseline, 34 percent of elderly participants had dementia. Nineteen percent of the dementia patients (618 participants)used antipsychotic medications. This included in-home or institutional care, and about three percent of the non-demented elderly population used antipsychotic medications as well. In both populations age and gender were similar. At a fouryear follow-up, the death rate in the antipsychotic use population was 64 percent and in the non-use group it was 67 percent. There were no differences noted in smoking, BMI, stroke, diabetes, hypertension, heart attack, and COPD. It appeared from this study that the use of antipsychotic medications in the very old with dementia did not seem to be associated with a higher mortality over four years.
Synthesis: This is an important finding since it appears that there is (in this limited study) no higher mortality with the use of antipsychotic medication. Antipsychotic medications have taken a hit from the FDA and interest groups because of the reported higher mortality in some studies and cardiovascular complications. This study does not mean we should be using antipsychotics indiscriminately, but in elderly patients who present with significant behavioral and psychotic features, it appears to be relatively safe to use these medications in appropriately small doses as necessary.
■ Norton, et al., had an interesting paper entitled “Spousal Dementia Care Giving as a Risk Factor for Incident Dementia.” This was part of the Cache County memory study, which enrolled 5,092 persons age 65 and older, beginning in 1995 and ongoing. This study looked at spouses who were caregivers for their demented spouses. There were 1,221 couples equaling 2,442 subjects. Incident dementia was documented for subjects and their spouses. Incident dementia was diagnosed in 255 subjects (221 had a dementia-free spouse and 34 whose spouse had incident dementia). They found that the caregiving spouse has a six-fold increase in the hazard for incidental dementia in relation to subjects whose spouses were dementia free. This risk was identical for men and women, and this conclusion was still present after the effect of other factors risking dementia was removed.
Synthesis: We have all known for years that the stress and burden on caregivers can often lead to a shortened life span with development of numerous other medical problems, such as depression, cardiovascular disease, and worsening hypertension. This study suggests that another risk of caregiver burden is the higher risk of developing Alzheimer's disease. This is an important message for clinical neurologists who treat dementia patients. We must do all we can to decrease caregiver burden and stress, which includes ongoing education about the disorder, encouraging caregivers to attend support groups or get individual counseling from a psychologist, home health care consultations, recommending antidepressant or anti-anxiety medication either through their family physician or under your care if they are also your patient, and encouraging reduction of Alzheimers risk factors, such as through increased exercise and aggressive treatment of hypertension, diabetes, high cholesterol, and smoking.
■ Colleen E. Jackson was author of a paper entitled “Dementia Literacy: Public Understanding of Known Risk Factors in Dementia.” Her team studied 676 adults in an on-line survey. The mean age of the public was 50, and 24 percent were male. Eightyseven percent were identified as well educated. The study found that there was a poor understanding of the relationship of dementia to a number of factors, including cardiovascular risks. Results showed that 61 percent of those surveyed stated there was no association of obesity or high blood pressure to dementia. Forty percent had no knowledge that physical exercise was protective for Alzheimer's disease. Only 50 percent believed that Alzheimer's disease reduces life span, and 95 percent believed that Alzheimer's disease was not related to aging and not curable.
Synthesis: For practicing neurologists this message that tells us that a goodly portion of the public have insufficient knowledge of Alzheimer's disease. I believe it is part of our duty as physicians to educate family members and older children about the risk factors that can worsen and be a contributing factor to the development of Alzheimer's disease. Despite the increasing public attention to Alzheimer's disease in the last 10 years, it is surprising that so many of the population have limited knowledge of this disorder. In my opinion, some of this lack of or misinformation on Alzheimers disease can be attributed to the media (see my comments in the callout box on p. 48).
*All abstracts and poster presentations are available in: The Journal of the Alzheimers Association; July 2009; 5(4)Supplement. They are also available online at: www.alzheimersanddementia.org/issues/contents (click the “next issue” arrow to view the supplement and articles).