Abstracts

Antioxidant intervention

Reactive oxygen metabolites (ROM), namely superoxide and hydroxyl free radicals and hydrogen peroxide, are produced as a consequence of the physiological metabolic reactions and functioning of the central nervous system. ROM have also been implicated in the aetiopathogenic processes of a number of pathological conditions of the brain; such as Parkinson's disease, Alzheimer's dementia, multiple sclerosis, and lipofuscinosis.

Therapeutic benefits are now being foreseen for a variety of antioxidant nutritional and pharmacological interventions.

Evans-PH Free radicals in brain metabolism and pathology. Br-Med-Bull. 1993 Jul; 49(3): 577-87

Body Weight

There are reports of weight loss and low body mass index (BMI) in patients with AD. The mesial temporal cortex (MTC) is involved in feeding behavior and memory and is preferentially involved in AD.

Low BMI correlates best and specifically with MTC atrophy. This finding supports a connection between limbic system damage and low body weight in AD.

Grundman-M et al: Low body weight in Alzheimer's disease is associated with mesial temporal cortex atrophy. Neurology. 1996 Jun; 46(6): 1585-91.

Chemosensory Perception

Chemosensory perception (1)

The elderly person's perception of foods and food flavor is affected by age-associated changes in the chemical senses (taste, smell, and trigeminal sensation).

Both normal elderly and patients with Alzheimer's disease show impairment in odor memory. Sensitivity to, familiarity with, and identifiability of the odors all play a role in odor memory performance. Flavor preference also changes over the lifespan. Older subjects, for instance, rate high concentration of sugar and salt as pleasanter than young subjects do. Multiple influences contribute to this phenomenon.

Elderly persons and those of lower nutritional status have shown preferences for higher concentrations of casein hydrolysate than young persons and those of higher nutritional status, suggesting that dietary preference can be related to chemosensory cues. There are significant age-associated changes in chemosensory perception that have the potential to interact with dietary selection and nutrition in the elderly. A better understanding of these phenomena may promote health and well-being in the elderly.

Murphy-C.: Nutrition and chemosensory perception in the elderly. Crit-Rev-Food-Sci-Nutr. 1993; 33(1): 3-15.

Chemosensory perception (2)

The design of foods for the elderly that could both compensate for these chemosensory losses and meet nutritional needs presents new challenges and opportunities for the food industry.

Schiffman-SS: Perception of taste and smell in elderly persons. Crit-Rev-Food-Sci-Nutr. 1993; 33(1): 17-26.

Energetics

Energy requirements

Energy intake and resting energy expenditure in relation to body composition were studied in female patients with Alzheimer's disease, multi-infarct dementia and in home-living non-demented elderly women.

Patients with Alzheimer's disease tended to have lower body weight and higher energy intake than control subjects or patients with multi-infarct dementia. Resting energy expenditure did not differ significantly between the groups (1089 +/- 129 kcal/day for patients with Alzheimer's disease, 1078 +/- 102 kcal/day for patients with multi-infarct dementia and 1188 +/- 143 kcal/day for control women; mean +/- SD).

Energy expenditure did not differ between the groups when calculated in relation to body weight or lean body mass. Resting energy expenditure was not increased in institutionalized female patients with long-standing Alzheimer's disease but they tended to have low body weight despite a high energy intake.

Niskanen-L. et al: Resting energy expenditure in relation to energy intake in patients with Alzheimer's disease, multi-infarct dementia and in control women. Age-Ageing. 1993 Mar; 22(2): 132-7.

Ethics

This article describes a situation in practice where the patient's difficulties in swallowing became an ethical dilemma for her family and the author. The incident caused the author to reflect on practice and look for ways to improve, by reviewing the relevant literature.

Clibbens R Eating, ethics and Alzheimer's. Nurs Times, 1996 Dec 11-17, 92:50, 29-30.

Genetic influences

Genetic influences on aluminum deposition

Aluminum is a known neurotoxin and has been suggested to play a role in the development of Senile Dementia of the Alzheimer's Type. The relationship between aluminum exposure and senile dementia cannot be a simple one, however, as not all exposure results in neurotoxic manifestations.

Findings suggest that there are genetic differences in the permeability of the blood brain barrier and lend support to the hypothesis that variability in aluminum toxicity may be, in part, genetically determined.

Fosmire-GJ et al: Genetic influences on tissue deposition of aluminum in mice. Biol-Trace-Elem-Res. 1993 May-Jun; 37(2-3): 115-21.

Glaucoma

Evidence is presented that the characteristic pattern of neuronal degeneration associated with glaucoma is due to a combination of the persistent physical damage to axons at the level of the lamina cribrosa and the associated neuronal reaction to this kind of trauma.

The class of neuronal cytoskeletal proteins known as the neurofilament triplet are crucially involved in the reaction to physical damage and the selective localization of these proteins to larger retinal ganglion cells may underlie their susceptibility to eventual degeneration.

The appearance of glaucoma-like neuronal pathology in Alzheimer's disease may follow the reaction of neurofilament-containing retinal ganglion neurons to persistent damage to their axons by beta-amyloid plaque formation in subcortical visual centers.

Vickers JC: The cellular mechanism underlying neuronal degeneration in glaucoma: parallels with Alzheimer's disease. Aust N Z J Ophthalmol, 1997 May, 25:2, 105-9.

Glucose metabolism

Glucose metabolism is depressed in the temporal and parietal regions of the cortex in patients with Alzheimer's disease. We measured the concentrations of two glucose transporters, GLUT1 and GLUT3, in six regions of brains from both control subjects and patients with Alzheimer's disease.

The concentrations of both transporters were reduced in the cerebral cortex, with larger and highly significant reductions observed for GLUT3, the putative neuronal glucose transporter.

The reductions in GLUT3 were greater than the loss of synapses, and should be considered as a potential cause of the deficits in glucose metabolism.

Simpson-IA et al: Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease [see comments]. Ann-Neurol. 1994 May; 35(5): 546-51

Brain iron

Iron in the brain

The location and function of iron in the central nervous system are reviewed with particular emphasis on human biology. Iron is distributed to different cell types in the brain in a heterogeneous fashion through the action of transferrin, transferrin receptors, and the metabolic needs of those cells. The function of this iron and its storage is documented in states of growth and development as well as during pathological states associated with aging. The information relating this biology to current observations of attention deficits in iron-deficient humans is also reviewed.

Beard-JL et al: Iron in the brain. Nutr-Rev. 1993 Jun; 51(6): 157-70.

Nutrition support

Alzheimer's disease is no longer considered an inevitable consequence of the aging process. The etiology is complex, involving several genes and possible environmental factors. Nutrition support is important in the treatment of people with Alzheimer's disease.

Folstein M Nutrition and Alzheimer's disease. Nutr Rev, 1997 Jan, 55:1 Pt 1, 23-5.

Phospholipids

Choline is involved in methyl group metabolism and lipid transport and is a component of a number of important biological compounds including the membrane phospholipids lecithin, sphingomyelin, and plasmalogen; the neurotransmitter acetylcholine; and platelet activating factor.

Disruptions in phospholipid metabolism can interfere with this process and may underlie certain disease states such as cancer and Alzheimer's disease. These recent findings may be appropriate in the consideration of choline as an essential nutrient for humans.

Canty-DJ & Zeisel-SH: Lecithin and choline in human health and disease. Nutr-Rev. 1994 Oct; 52(10): 327-39

Residence quality

Quality of residential care

The availability and an assessment of the nutritionally-relevant information from 100 medical records of ambulatory residents in ten special care units (SCU) for Alzheimer's patients was determined. Eight facilities had estimated calorie and fluid needs and four estimated protein needs of residents. Over 40% of the residents were underweight and significant weight loss was reported for 20%.

Hemoglobin, hematocrit and albumin were 8% lower and cholesterol was 24% higher than the levels associated with high death rates among institutionalized elderly. Many factors existed placing patients at high risk for malnutrition.

Facilities monitored the nutritional status of Alzheimer's patients to a variable extent.

Zahler-LP et al: Nutritional care of ambulatory residents in special care units for Alzheimer's patients. J-Nutr-Elder. 1993; 12(4): 5-19.

Weight loss

Weight loss (1)

Alzheimer's disease affects an estimated 2 million elderly in the U.S. and challenges primary care physicians to assist caregivers in dealing with the daily management of these patients. To support the clinical observation of weight loss in Alzheimer patients despite adequate food intake, we reviewed the existing literature.

Finally, some reports lead to speculation that nutritional strategies may improve cognitive function.

Wolf-Klein-GP & Silverstone-FA Weight loss in Alzheimer's disease: an international review of the literature. Int-Psychogeriatr. 1994 Fall; 6(2): 135-42

Weight loss (2)

Weight loss in Alzheimer's patients has been observed by many clinicians and reported in the international geriatric literature. It represents a puzzling challenge for clinicians and researchers, and it is an important issue for caregivers and nursing home staff concerned with state and federal requirements for nutrition and weight monitoring.

Compared with MID patients, Alzheimer's patients tended to weigh less (52.84 vs 56.4 kg; p = 0.20) but actually required more calories (1626 vs 1341 kcal, p < 0.011).(

Wolf-Klein-GP et al: Energy requirements in Alzheimer's disease patients. Nutrition. 1995 May-Jun; 11(3): 264-8

Erythrocytes

An increase in erythrocyte-bound IgG and enhanced breakdown of the erythrocyte anion exchanger band 3, characteristics of normal erythrocyte aging are observed in old, healthy individuals when compared with young donors. These findings indicate that the rate of cellular aging increases with organismal aging.

Results from previous studies on the same parameters have suggested that the erythrocyte aging process is disturbed in patients in advanced stages of Alzheimer type dementia, and in individuals with Down's syndrome who show no signs of dementia. In this study we find no changes in erythrocyte aging parameters in old individuals in beginning stages of dementia of various etiologies.

In general, characteristics of disturbed erythrocyte aging cannot serve as presymptomatic markers of Alzheimer-type dementia.

Bosman GJ Erythrocyte aging characteristics in elderly individuals with beginning dementia. Neurobiol Aging, 1997 May-Jun, 18:3, 291-5.

Vitamin E

Conducted a double-blind, placebo-controlled, randomized, multicenter trial in patients with Alzheimer's disease of moderate severity. A total of 341 patients received the selective monoamine oxidase inhibitor selegiline (10 mg a day), alpha-tocopherol (vitamin E, 2000 IU a day), both selegiline and alpha-tocopherol, or placebo for two years. The primary outcome was the time to the occurrence of any of the following: death, institutionalization, loss of the ability to perform basic activities of daily living, or severe dementia (defined as a Clinical Dementia Rating of 3).

After an average of 440 days, at least one of these things had happened to the people taking placebos. However, these events took 230 days longer to happen to those on vitamin E and 215 days longer for those taking selegiline.

For reasons that the researchers could not explain, the patients using the two drugs together fared considerably worse. Their slide was delayed by just 145 days.

"It reminds us that two drugs are not necessarily better than one," Sano said.

Sano M et al., A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. [see comments] NEJM, 1997 Apr, 336:17, 1216-22.

Increased Blood Mercury Levels

Increased Blood Mercury Levels

Alzheimer's patients exhibit blood mercury levels more than twofold higher than those of control groups.
In early onset Alzheimer's disease patients, the mercury levels were almost threefold higher as compared to controls. These results demonstrate elevated blood levels of mercury in Alzheimer's disease and suggest that the increase in mercury is associated with high cerebral spinal fluid levels of amyloid beta-peptide. The source of the elevated blood mercury may be an unidentified environmental source or mercury may be released from brain tissue with advanced neuronal death.

Hock, C., et al: Increased Blood Mercury Levels in Patients With Alzheimer's Disease, Journal of Neural Transmission, 1998;105:59-68.

Acetyl-L-Carnitine

Acetyl-L-Carnitine

Acetyl-L-Carnitine may have beneficial effects on the neurochemical aspects of Alzheimer's disease (AD). In a study, AD patients taking this agent had greater mental capability than in the placebo group as measured by Mini-Mental Status and Alzheimer's Disease Assessment Scale test scores. Also, phosphomonoester levels and high-energy brain phosphate levels were normalized in patients on acetyl-L-carnitine but not in placebo-treated patients. This is the first successful in vivo study of the beneficial effects of a drug on clinical and neurochemical parameters in Alzheimer's disease .

Pettegrew JW, Klunk WE, Panchalingam K, Kanfer JN, McClure RJ. Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease. Neurobiol Aging 1995 Jan-Feb;16(1):1-4.


Acetyl levocarnitine may slow the deterioration of some cognitive areas in patients with Alzheimer's disease. This double-blind, parallel design study observed 30 patients receiving either acetyl levocarnitine hydrochloride or placebo treatment for a total of 6 months. The acetyl levocarnitine group had significantly less deterioration in timed cancellation tasks and Digit Span (forward), and notably less deterioration in timed verbal fluency task. No differences between placebo and acetyl levocarnitine groups were found in any other neuropsychological test results. A subgroup with the lowest baseline scores showed significantly less deterioration on the verbal memory test and significantly increased levels of acetyl levocarnitine in the cerebrospinal fluid. A larger study of acetyl levocarnitine is strongly recommended.

Sano M, Bell K, Cote L, Dooneief G, Lawton A, Legler L, Marder K, Naini A, Stern Y, Mayeux R. Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's disease. Arch Neurol 1992 Nov;49(11):1137-41.


In a clinical trial, long-term acetyl-L-carnitine treatment slowed the rate of deterioration in 13 of 14 outcome measures of functional and cognitive impairment. After adjusting for initial scores with analysis covariance, the group treated with acetyl-L-carnitine Reported adverse events were mild, with no difference in incidence or severity between the treated and placebo groups.

Spagnoli A, Lucca U, Menasce G, Bandera L, Cizza G, Forloni G, Tettamanti M, Frattura L, Tiraboschi P, Comelli M, et al. Long-term acetyl-L-carnitine treatment in Alzheimer's disease. Neurology 1991 Nov;41(11):1726-32.

High Blood Pressure & High cholesterol

High blood pressure and high cholesterol

According to this random population based sample study, increases in systolic blood pressure and/or serum cholesterol concentrations during midlife may be related to an increased risk for developing Alzheimer's disease. The authors had 1,449 subjects from eastern Finland that had participated in past surveys and an average of 21 years worth of follow ups take part in a 1998 re-examination. Serum cholesterol levels and the systolic and diastolic blood pressures of the 67 to 79 year-old subjects were measured to determine if there was a correlation between increased blood pressure and/or cholesterol during midlife and increased risk of Alzheimer's. It was found that the participants who exhibited increased systolic blood pressure or serum cholesterol concentrations in midlife had a significantly higher risk of developing Alzheimer's disease. An increase in both of these factors led to an even greater risk of Alzheimer's. No correlation between changes in diastolic blood pressure and risk of Alzheimer's was found.

Kivipelto M, et al: Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study, BMJ 2001 Jun 16;322(7300):1447-51

HDL cholesterol

HDL cholesterol

High levels of HDL cholesterol in later life may correspond to greater incidence of Alzheimer's disease, according to this study on Japanese-American men. The cholesterol levels of 218 men involved in the Honolulu-Asia Aging Study were measured in late life (average age of death was 84.6 years) as well as in 89 men twenty years prior to late life. The number of neuritic plaques and neurofibrillary tangles, which are characteristic of Alzheimer's, were counted in the neocortex and the hippocampus of each participant postmortem. A strong correlation between increased late-life HDL cholesterol and higher numbers of neocortical neuritic plaques and hippocampal and neocortical neurofibrillary tangles was found after the data was controlled for several variables, including death, education, and blood pressure. This correlation was also found for midlife levels of HDL-cholesterol. These results indicate that HDL-cholesterol may play some role in developing the physiological markers of Alzheimer's disease.
        
Launer LJ, White LR, Petrovitch H, Ross GW, Curb JD: Cholesterol and neuropathologic markers of AD: a population-based autopsy study, Neurology 2001 Oct 23;57(8):1447-52