HomeLarge Type Edition
HOME ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text (PDF)
Services
Right arrow Download to citation manager
PubMed
Right arrow PubMed Citation
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 58:M314-M321 (2003)
© 2003 The Gerontological Society of America

EDITORIAL

Memories Are Made of This: Recent Advances in Understanding Cognitive Impairments and Dementia

William A. Banks and John E. Morley

Geriatric Research Education and Clinical Center, St. Louis VA Medical Center, Missouri, and Division of Geriatric Medicine, Saint Louis University, St. Louis, Missouri.

"... during the paroxysms of fever, patients are delirious and talk nonsense (desipere et loqui aliena). But insanity is really when a continuous dementia begins, when the patient, although up until then in his senses ... (continua dementia ess accepit)."

Celsius, 1st Century AD

COGNITIVE impairment becomes more common with advancing age. In a study of over 1000 physicians, there was an 18% decline in the total cognitive score between 40 to 70 years of age (1). However, variability within the group was 60% greater in the 70-year-olds compared to the 40-year-olds. Areas in which age-related declines are often more prominent are learning of new information with practice and the speed of motor performance. Cognitive decline represents a major factor involved in the pathogenesis of age-related frailty (2–6) and functional decline (7–12). Intellectual disability is associated negatively with life expectancy (13,14).

When a person has had a decline in cognitive dysfunction they become more vulnerable to the development of delirium when they develop physical illnesses. Persons with delirium often present with new-onset falls (15–17), and thus new-onset falls should be considered a delirium equivalent. Delirium is poorly recognized by health care professionals (18) and often has more than one cause (19–21), and, as such, requires the health care physician to carefully evaluate the patient with delirium for multiple possible etiological factors. Persons with delirium often have an elevated circulating level of anticholinergic activity (22). As acetylcholine is an important neurotransmitter involved in the genesis of learning and recall, this suggests that inhibition of acetylcholinergic pathways may be an important end pathway in the pathogenesis of delirium. Many drugs that are not classically considered to be anticholinergic, such as digoxin, theophylline, and amantidine, are highly anticholinergic in in vitro assays (23). This explains why polypharmacy, which remains a major problem in older persons (24,25), is such a potent cause of delirium. Infection produces its cognitive impairment predominantly by the release of cytokines. Cytokines produce cognitive impairment by inhibiting acetylcholine function in the central nervous system, both by directly crossing the blood–brain barrier and by stimulating ascending autonomic nervous system fibers (26,27). The major causes of delirium along with the causes of reversible dementia are listed in Table 1. Recent studies have suggested that an interdisciplinary team focused on delirium (28) or a delirium intensive care unit (29) can greatly improve the outcomes of patients with delirium.


View this table:
[in this window]
[in a new window]
  		Table 1. Mnemonics for the Conditions Causing Delirium and Reversible Dementia.

 
Over the last decade, the understanding that a number of persons have mild cognitive impairment (MCI) has become well established (30). These individuals have complaints and objective evidence of memory problems without deficits in activities of daily living. While classically these persons are not supposed to have depression, recent studies have suggested that neuropsychiatric complaints are not rare in MCI (31). Thus, treatment of depression is a key component of the management of MCI and early dementia (32). Patterns location association learning is a test that appears to be particularly sensitive to diagnosing MCI (33). Mild cognitive impairment is not benign, with death occurring in approximately one third of patients and another third progressing to dementia of the Alzheimer's type within 5 years of diagnosis (34). Persons with MCI who have a major event such as a hip fracture, myocardial infarction, or coronary artery bypass surgery tend to have poorer functional recovery than persons with normal age-related cognitive impairment. Figure 1 provides the Saint Louis University Mental Status (SLUMS) examination developed to help recognize MCI.



View larger version (68K):
[in this window]
[in a new window]
  		Figure 1. Rapid screening test for cognitive impairment

 
A number of attempts have been made to increase the diagnostic accuracy of persons with MCI who are going to progress to Alzheimer's disease (AD). Utilizing neuroimaging, persons with MCI who have smaller hippocampal volumes (35) or decreased blood flow to the posterior cingulated gyrus (36) are more likely to progress to AD. Persons with an increase in tau protein and a decrease in beta-amyloid [1–42] in the cerebrospinal fluid (CSF) have an increased likelihood of developing AD (37). The recent demonstration that tau levels in oral epithelium are reflective of CSF tau levels may provide an easy noninvasive method to detect those at risk for AD (38).

Treatment trials of MCI with acetylcholinesterase inhibitors are underway. Despite the generally negative associations of estrogen use with the development of AD, nevertheless biochemical and animal studies suggest a possible use of estrogen in slowing the progression of MCI (39–45). The gradual decline of testosterone in males with aging has been associated with cognitive decline (46–53). Testosterone replacement has resulted in improvement of age-related memory dysfunction in some (54–56), but not all, studies (57,58). Testosterone improved memory in the SAMP8 mouse, an animal model of cognitive decline associated with overproduction of beta-amyloid protein (59). Other hormones such as pregnenolone and dehydroepiandrosterone (DHEA) have produced dramatic improvement of memory in animals, but minimal effects in humans (60,61).

Alzheimer's Disease
The first descriptions of a disease similar to AD were published in the 18th century. However, it wasn't until Alois Alzheimer described the association of cognitive impairment with amyloid plaques in relatively young persons in 1907 that the disease became firmly established (62). These findings suggested that it was the amyloid plaque that was responsible for the disease and generated the amyloidocentric theories of AD. Modern thought processes have moved away from the concept that the amyloid plaque is neurotoxic to the concept that soluble oligomeric forms of beta-amyloid produce memory disturbance (63–65), and in complex with apolipoprotein E or by themselves, generate free radicals and are neurotoxic (66).

Three genes have been associated with early-onset AD. These are amyloid precursor protein (APP) on chromosome 21, presenilin 1 on chromosome 14, and presenilin 2 on chromosome 1. The mutations on presenilin 1 are the most common cause of familial AD. Presenilin mutations lead to altered processing of APP by activating gamma-secretase, resulting in a disproportionate production of beta-amyloid [1–42]. APP is a type 1 transmembrane glycoprotein that has a small cytoplasmic tail, a transmembrane portion, and a large extracellular region. Mutations that produce AD either reduce alpha-secretase activity or increase gamma-secretase activity, resulting in increased production of beta-amyloid [1–42] (67,68).

Apolipoprotein E is a lipid transport protein whose gene is located on chromosome 19. The E4 allele of apolipoprotein E increases the risk of late-onset AD and the E2 allele decreases the risk (69,70). The E4 allele is also associated with an increase in cardiovascular disease. Apolipoprotein E complexes with beta-amyloid, reducing its transport out of the brain and resulting in formation of insoluble plaques, neuroinflammation, and possibly phosphorylation of tau protein (66,71).

Aside from amyloid plaques, the pathological diagnosis of AD requires the presence of neurofibrillary tangles. In AD, these are produced by hyperphosphorylation of tau protein possibly secondary to overproduction of beta-amyloid. However, tauopathies with neurofibrillary tangles can be seen in other neurodegenerative disorders such as frontotemporal dementia with Parkinsonism linked to chromosome 17 (Pick's disease). It is characterized by personality changes, altered executive function, personality changes, bradykinesia, and rigidity (72).

There is increasing evidence that decreased clearance of beta-amyloid from the central nervous system plays an important role in the pathogenesis of AD (73). Thus, it is not surprising that genetic mutation of the genes for {alpha}2-macroglobuilins and lipoprotein-related protein, which are involved in clearance of proteins from the brain, have been associated with AD. At present, studies are ongoing examining the effectiveness of low-flow CSF drainage for the treatment of AD (74).

Animal Models of AD
Mouse models that either spontaneously overproduce beta-amyloid (SAMP8) or are transgenics that overproduce human beta-amyloid have allowed major advances in our understanding of the pathophysiology of AD. The 3 transgenic mice are the "Games mouse" (75), the "Hsiao mice" (76), and the "Novartis mouse" (77). Each of these transgenic models produced beta-amyloid plaques and neuritic changes. They do not develop tau-positive neurofibrillary tangles. Memory impairment occurred at 9 to 10 months. When mice that overexpress human amyloid precursor protein are mated with mice lacking apolipoprotein E, there is a marked decrease in beta-amyloid deposits (78).

The SAMP8 is a mouse model that spontaneously overproduces beta-amyloid (79–83). The SAMP8 mouse develops memory and learning deficits at 8 to 10 months of age. Beta-amyloid plaques develop late at 15 to 16 months. The memory deficits can be reversed by administration of antibodies to beta-amyloid (84) or by an antisense to the mRNA for amyloid precursor protein that reduces beta-amyloid production (85,86). SAMP8s show abnormalities in acetylcholine function and other neurotransmitters including glutamate, gamma aminobuteric acid, and serotonin (87). SAMP8s also have an increase in oxidative stress (88).

The data from animal models strongly support the concept that overproduction of beta-amyloid is key to the pathogenesis of AD. These models suggest that plaque formation occurs late and may be an epiphenomenon.

Nutrition and Dementia
Protein energy malnutrition is common in older persons and is associated with cognitive decline (89–91). Equally, persons with cognitive impairment are at high risk for decreasing food intake and weight loss (92–94). Thus, paying special attention to the nutritional needs of older individuals with dementia, such as recognizing the shifts in circadian rhythm of eating patterns (95,96), paying attention to alterations in taste and smell (97,98) [patients with AD develop anosmia (99)], and providing adequate amounts of time to allow them to feed adequately (100), are all key to maintaining cognitive function.

The reasons for cognitive decline associated with malnutrition are multifactorial and include not only vitamin and mineral deficiencies, but also the fact that food releases gastrointestinal hormones that enhance memory (101,102). Thus, cholecystokinin, a gut hormone, is a potent enhancer of memory that produces its effects by activating ascending vagal fibers that, through a number of relays, modulate the ability to recall memories in the amygdala and hippocampus (103–105).

Elevated homocysteine levels are associated with AD. There are a number of causes of elevated homocysteine levels, including vitamin B12 and B6 deficiency, folate deficiency, renal failure, hypothyroidism, estrogen deficiency, and congenital causes (106). Vitamin B12 replacement in persons with mild cobalamin deficiency improved verbal fluency and electrographic signs of cerebral function (107). These improvements were associated with a decline in homocysteine.

It is now recognized that lipid content of neuronal membranes plays a key role in the function of neurotransmitters. The SAMP8 mouse has a decrease in {Delta}9 desaturase activity, leading to an increase in brain saturated fatty acids compared to unsaturated fatty acids (108). A diet rich in polyunsaturated fatty acids enhances memory function in the SAMP8 mouse (109). Caloric restriction has been demonstrated in rodents to have a number of beneficial metabolic effects that extend life (110–113). In addition, caloric restriction enhances membrane fluidity (114), and this is associated with improved acquisition and memory (115).

Recent studies have demonstrated that treatment with 3-hydroxy-3-methylgluaryl-coenzyme A reductase inhibitors (statins) are associated with a lower prevalence of cognitive impairment (116). Whether these effects are due to enhanced membrane fluidity or secondary to a reduction in vascular disease remains to be determined (117,118). Apolipoprotein E is a cholesterol-lowering protein, and this provides a link between cholesterol lowering and AD.

Persons with diabetes mellitus have cognitive and functional impairment (119–121). While in many cases this is due to vascular disease, it has also been demonstrated both in animals (122) and humans (123,124) that elevated glucose levels per se can cause a decline in cognitive function.

Finally, much data has accumulated to implicate oxidative stress and free radical damage in the progression of dementia (72). Vitamin E slows progression of dementia (125). Alpha-lipoic acid is a particularly potent free radical scavenger that may prove of use in delaying progression of AD.

Management of AD
The majority of persons with dementia will have AD, with lesser numbers having reversible dementias (Table 1) and vascular dementia. It is likely that dementia of the frontal lobe type and Lewy-body dementia are underdiagnosed. Figure 2 gives a simple approach to the diagnosis of dementias. Persons with frontal lobe dementia, besides having more behavioral problems, perform worse on letter and category fluency and better on memory and clock drawing tests than do patients with AD. A number of tests to help confirm the diagnosis of AD show promise. These include hippocampal volume, elevated levels of tau in the CSF and lips, measurement of ALZAS (Alzheimer Associated Protein), imaging of beta-amyloid plaques, and PET (positron emission tomography) scan measurement of frontal lobe metabolic activity (38,126–129). Chan (130) has suggested that dementia could be recognized earlier if the rate of decline in cognitive function is taken into account.



View larger version (12K):
[in this window]
[in a new window]
  		Figure 2. Algorithm for diagnosis of dementia

 
Most of the drugs presently used to treat AD were developed in response to the cholinergic hypothesis as outlined in the article by Grossberg and Desai in this issue of the Journal (131). These drugs produce small improvements in cognition (somewhat less of an improvement than the gain seen when earwax is removed from a demented person), delay the progression of the disease, and possibly decrease behavior disturbances: It is important to recognize that although not tested with similar batteries, studies have consistently reported that ergot alkaloids such as nicergoline and hydergine appear to be equally effective in the treatment of dementia (132–136).

Memantine is a drug approved in Europe for the treatment of AD (137). This drug works by modulating the glutamate/n-methyl-D-aspartate system. Preliminary results suggest that it may function as well or slightly better than the acetylcholinesterase inhibitors. Trials of a vaccine against AD produced brain inflammation (138,139). A pilot study utilizing vagal nerve stimulation has reported a positive effect in persons with AD (140).

Many older persons utilize complementary medicines (141–145). One of these is gingko biloba, which appears to have positive effects according to an article in the Journal by Andrieu and colleagues (146). Wittstein, in a meta-analysis, concluded that gingko special extract is equivalent to donepezil and rivastigmine (147). Other studies have found efficacy for gingko (148).

As has been chronicled in the pages of the Journal, appropriate therapy for dementia includes not only treatment aimed at the dementia but also treatment of medical comorbid conditions (149), appropriate nutritional and exercise support (150–152), care of pain management (153,154), caregivers (155–157), and appropriate end-of-life care (155). Thus, hip fracture is classically associated with functional decline (158,159). However, a recent study showed that intensive therapy in hip fracture patients with dementia can result in a high proportion returning to the community (160). Finally, it is important to recognize that antipsychotic agents only have small effects on behavioral disturbances in demented individuals, and in many individuals have no effect at all on behavior (161–163). The appropriate first line of management of behavioral abnormalities is education of the caregivers and behavioral management. Programs such as the Eden Alternative and pet therapy can be far more effective in modifying behavior than antipsychotics (164–166).

References

  1. Powell DH. Profiles in Cognitive Aging. Cambridge, MA: Harvard University Press; 1994.
  2. Bortz WM, 2nd. A conceptual framework of frailty: a review. J Gerontol Med Sci.. 2002;57A:M283-M288.[Abstract/Free Full Text]
  3. Morley JE, Perry HM, III, Miller DK. Something about frailty. J Gerontol Med Sci.. 2002;57A:M698-M704.[Free Full Text]
  4. Lipsitz LA. Dynamics of stability: The physiologic basis of functional health and frailty. J Gerontol Biol Sci.. 2002;57A:B115-B125.[Abstract/Free Full Text]
  5. Gillick M. Pinning down frailty. J Gerontol Med Sci.. 2001;56A:M134-M135.[Free Full Text]
  6. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol Med Sci.. 2001;56A:M146-M156. Newman AB, Gottdiener JS, McBurnie MA, et al. Associations of subclinical cardiovascular disease with frailty. J Gerontol Med Sci.. 2001;56A:M158-M166.[Abstract/Free Full Text]
  7. Raji MA, Ostir GV, Markides KS, Goodwin JS. The interaction of cognitive and emotional status on subsequent physical functioning in older Mexican Americans: findings from the Hispanic established population for the epidemiologic study of the elderly. J Gerontol Med Sci.. 2002;57A:M678-M682.[Abstract/Free Full Text]
  8. Blaum CS, Ofstedal MB, Liang J. Low cognitive performance, comorbid disease, and task-specific disability: findings from a nationally representative survey. J Gerontol Med Sci.. 2002;57A:M523-M531.[Abstract/Free Full Text]
  9. Njegovan V, Man-Son-Hing M, Mitchell SL, Molnar FJ. The hierarchy of functional loss associated with cognitive decline in older persons. J Gerontol Med Sci.. 2001;56A:M638-M643.[Abstract/Free Full Text]
  10. Sands LP, Yaffe K, Lui LY, Stewart A, Eng C, Covinsky K. The effects of acute illness on ADL decline over 1 year in frail older adults with and without cognitive impairment. J Gerontol Med Sci.. 2002;57A:M449-M454.[Abstract/Free Full Text]
  11. Thomas DR. Focus on functional decline in hospitalized older adults. J Gerontol Med Sci.. 2002;57A:M567-M568.[Free Full Text]
  12. Miller DK, Lui LYL, Perry HM, Kaiser FE, Morley JE. Reported and measured physical functioning in older inner-city diabetic African Americans. J Gerontol Med Sci.. 1999;54A:M230-M236.[Abstract]
  13. Bittles AH, Petterson BA, Sullivan SG, Hussain R, Glasson EJ, Montgomery PD. The influence of intellectual disability on life expectancy. J Gerontol Med Sci.. 2002;57A:M470-M472.[Abstract/Free Full Text]
  14. Carlson MC, Brandt J, Steele C, Baker A, Stern Y, Lyketsos CG. Predictor index of mortality in dementia patients upon entry into long-term care. J Gerontol Med Sci.. 2001;56A:M567-M570.[Abstract/Free Full Text]
  15. Morley JE. A fall is a major event in the life of an older person. J Gerontol Med Sci.. 2002;57A:M492-M495.[Free Full Text]
  16. Redfern MS, Muller ML, Jennings JR, Furman JM. Attentional dynamics in postural control during perturbation in young and older adults. J Gerontol Biol Sci.. 2002;57A:B298-B303.[Abstract/Free Full Text]
  17. Fletcher PC, Hirdes JP. Risk factors for falling among community-based seniors using home care services. J Gerontol Med Sci.. 2002;57A:M504-M510.[Abstract/Free Full Text]
  18. Lewis LM, Miller DK, Morley JE, Nork MJ, Lasater LC. Unrecognized delirium in ED geriatric patients. Am J Emergency Med.. 1995;13:142-145.[Medline]
  19. Flacker JM, Lipsitz LA. Neural mechanisms of delirium: current hypotheses and evolving concepts. J Gerontol Biol Sci.. 1999;54A:B239-B246.[Abstract]
  20. McCusker J, Kakuma R, Abrahamowicz M. Predictors of functional decline in hospitalized elderly patients: a systematic review. J Gerontol Med Sci.. 2002;57A:M569-M577.[Abstract/Free Full Text]
  21. Dolan MM, Hawkes WG, Zimmerman SI, et al. Delirium on hospital admission in aged hip fracture patients: prediction of mortality and 2-year functional outcomes. J Gerontol Med Sci.. 2000;55A:M527-M534.[Abstract/Free Full Text]
  22. Flacker JM, Wei JY. Endogenous anticholinergic substances may exist during acute illness in elderly medical patients. J Gerontol Med Sci.. 2001;56A:M353-M355.[Abstract/Free Full Text]
  23. Tune L, Carr S, Hoag E, Cooper T. Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium. Am J Psychiatr.. 1992;149:1393-1394.[Abstract/Free Full Text]
  24. Flaherty JH, Perry HM, Lynchard GS, Morley JE. Polypharmacy and hospitalization among older home care patients. J Gerontol Med Sci.. 2000;55A:M554-M559.[Abstract/Free Full Text]
  25. Morley JE. Drugs, aging and the future. J Gerontol Med Sci.. 2002;57A:M2-M6.[Free Full Text]
  26. Banks WA, Farr SA, La Scola ME, Morley JE. Intravenous human interleukin-1 alpha impairs memory processing in mice: dependence on blood-brain barrier transport into posterior division of the septum. J Pharmacol Exp Ther.. 2001;299:536-541.[Abstract/Free Full Text]
  27. Banks WA, Moinuddin A, Morley JE. Regional transport of TNF-alpha across the blood-brain barrier in young ICR and young and aged SAMP8 mice. Neurobiol Aging.. 2001;22:671-676.[Medline]
  28. Inouye Sk, Bogardus ST, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med.. 1999;340:669-676.[Abstract/Free Full Text]
  29. Flaherty JH, Tariq S, Raghavan S, Bakshi S, Moinuddin A, Morley JE. A model for managing delirious older inpatients. J Am Geriatr Soc. In press.
  30. Larrieu S, Letenneur L, Orgogozo JM, et al. Incidence and outcome of mild cognitive impairment in a population-based prospective cohort. Neurology.. 2002;59:1594-1599.[Abstract/Free Full Text]
  31. Lyketsos CG, Lopez O, Jones B, Fitzpatrick AL, Breitner J, DeKosky S. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment—results from the Cardiovascular Health Study. JAMA.. 2002;288:1475-1483.[Abstract/Free Full Text]
  32. Blazer DA. Depression in late life: review and commentary. J Gerontol Med Sci.. 2003;58A:249-265.
  33. Collie A, Maruff P, Currie J. Behavioral characterization of mild cognitive impairment. J Clin Exp Neuropsychol.. 2002;24:720-733.[Medline]
  34. Bennett DA, Wilson RS, Schneider JA, et al. Natural history of mild cognitive impairment in older persons. Neurology.. 2002;59:198-205.[Abstract/Free Full Text]
  35. Grundman M, Sencakova D, Jack CR, et al. Brain MRI hippocampal of clinical status in a mild volume and prediction cognitive impairment trial. J Mol Neurosci.. 2002;19:23-27.[Medline]
  36. Killiany RJ, Hyman BT, Gomez-Isla T, et al. MRI measures of entorhinal cortex vs hippocampus in preclinical AD. Neurology.. 2002;58:1188-1196.[Abstract/Free Full Text]
  37. Riemenschneider M, Lautenschlager N, Wagenpfeil S, Diehl J, Drzezga A, Kurz A. Cerebrospinal fluid tau and beta-amyloid 42 proteins identify Alzheimer disease in subjects with mild cognitive impairment. Arch Neurol.. 2002;59:1729-1734.[Abstract/Free Full Text]
  38. Hattori H, Matsumoto M, Iwai K, et al. The tau protein of oral epithelium increases in Alzheimer's disease. J Gerontol Med Sci.. 2002;57A:M64-M70.[Abstract/Free Full Text]
  39. Petitti DB, Buckwalter JG, Crooks VC, Chiu V. Prevalence of dementia in users of hormone replacement therapy as defined by prescription data. J Gerontol Med Sci.. 2002;57A:M532-M538.[Abstract/Free Full Text]
  40. Ott BR, Belazi D, Lapane KL. Cognitive decline among female estrogen users in nursing homes. J Gerontol Med Sci.. 2002;57A:M594-M598.[Abstract/Free Full Text]
  41. Asthana S. Estrogen and cognition: the story so far. J Gerontol Med Sci.. 2003;58A:322-323.
  42. Whitmer RA, Haan MN, Miller JW, Yaffe K. Hormone replacement therapy and cognitive performance: the role of homocysteine. J Gerontol Med Sci.. 2003;58A:324-330.
  43. Watkins RA, Guariglia R, Kaye JA, Janowsky JS. Informants: knowledge of reproductive history and estrogen replacement. J Gerontol Med Sci.. 2001;56A:M176-M179.[Abstract/Free Full Text]
  44. Farr SA, Flood JF, Scherrer JF, Kaiser FE, Taylor GT, Morley JE. Effect of ovarian steroids on footshock avoidance learning and retention in female mice. Physiol Behav.. 1995;58:715-723.[Medline]
  45. Farr SA, Banks WA, Morley JE. Estradiol potentiates acetylcholine and glutamate-mediated post-trial memory processing in the hippocampus. Brain Res.. 2000;864:263-269.[Medline]
  46. Matsumoto AM. Andropause: clinical implications of the decline in serum testosterone levels with aging in men. J Gerontol Med Sci.. 2002;57A:M76-M99.[Free Full Text]
  47. Morley JE. Androgens and aging. Maturitas.. 2001;38:61-71.[Medline]
  48. Yaffe K, Lui LY, Zmuda J, Cauley J. Sex hormones and cognitive function in older men. J Am Geriatr Soc.. 2002;50:707-712.[Medline]
  49. Barrett-Connor E, Goodman-Gruen D, Patay B. Endogenous sex hormones and cognitive function in older men. J Clin Endocrinol Metab.. 1999;84:3681-3685.[Abstract/Free Full Text]
  50. Morley JE, Kaiser F, Raum WJ, et al. Potentially predictive and manipulable blood serum correlates of aging in the healthy human male—progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone. Proc Natl Acad Sci U S A.. 1997;94:7537-7542.[Abstract/Free Full Text]
  51. Moffat SD, Zonderman AB, Metter EJ, Blackman MR, Harman SM, Resnick SM. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab.. 2002;87:5001-5007.[Abstract/Free Full Text]
  52. Morley JE. Andropause: is it time for the geriatrician to treat it? J Gerontol Med Sci.. 2001;56A:M263-M265.[Free Full Text]
  53. Morley JE, Kaiser FE, Perry HM, et al. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metab Clin Exp.. 1997;46:410-413.
  54. Cherrier MM, Asthana S, Plymate S, et al. Testosterone supplementation improves spatial and verbal memory in healthy older men. Neurology.. 2001;57:80-88.[Abstract/Free Full Text]
  55. Janowsky JS, Chavez B, Orwoll E. Sex steroids modify working memory. J Cogn Neurosci.. 2000;12:407-414.[Medline]
  56. Wolf OT, Preut R, Hellhammer DH, Kudielka BM, Schurmeyer TH, Kirschbaum C. Testosterone and cognition in elderly men: a single testosterone injection blocks the practice effect in verbal fluency, but has no effect on spatial or verbal memory. Biol Psychiatr.. 2000;47:650-654.[Medline]
  57. Sih R, Morley JE, Kaiser FE, Perry HM, Patrick P, Ross C. Testosterone replacement in older hypogonadal men—a 12-month randomized controlled trial. J Clin Endocrinol Metab.. 1997;82:1661-1667.[Abstract/Free Full Text]
  58. Kenny AM, Bellantonio S, Gruman CA, Acosta RD, Prestwood KM. Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels. J Gerontol Med Sci.. 2002;57A:M321-M325.[Abstract/Free Full Text]
  59. Flood JF, Farr SA, Kaiser FE, Laregina M, Morley JE. Age-related decrease of plasma testosterone in SAMP8 mice—replacement improves age-related impairment of learning and memory. Physiol Behav.. 1995;57A:669-673.[Medline]
  60. Flood JF, Morley JE, Roberts E. Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it. Proc Natl Acad Sci U S A.. 1992;89:1567-1571.[Abstract/Free Full Text]
  61. Flood JF, Morley JE, Roberts E. Pregnenolone sulfate enhances post-training memory processes when injected in very low doses into limbic system structures—the amygdala is by far the most sensitive. Proc Natl Acad Sci U S A.. 1995;92:10806-10810.[Abstract/Free Full Text]
  62. Alzheimer L. Uber eine eigenastige. Erkangkung der Himrinde. All 2. Psychiatri.. 1907;64:146-148.
  63. Flood JF, Morley JE, Roberts E. An amyloid Beta-protein fragment, a beta[12–28], equipotently impairs post-training memory processing when injected into different limbic system structures. Brain Res.. 1994;663:271-276.[Medline]
  64. Flood JF, Morley JE, Roberts E. Amnestic effects in mice of four synthetic peptides homologous to amyloid beta protein from patients with Alzheimer disease. Proc Natl Acad Sci U S A.. 1991;88:3363-3366.[Abstract/Free Full Text]
  65. Flood JF, Roberts E, Sherman MA, Kaplan BE, Morley JE. Topography of a binding site for small amnestic peptides deduced from structure activity studies—relation to amnestic effect of amyloid beta-protein. Proc Natl Acad Sci U S A.. 1994;91:380-384.[Abstract/Free Full Text]
  66. Bales KR, Dodart JC, DeMattas RB, Hotzman DM, Paul SM. Apolipoprotein E, amyloid and Alzheimer disease. Mol Pharmacol.. 2002;2:363-375.
  67. Maiorini AF, Gaunt MJ, Jacobsen TM, McKay AE, Waldman LD, Raffa RB. Potential novel targets for Alzheimer pharmacotherapy: I. Secretases. J Clin Pharm Ther.. 2002;27:169-183.[Medline]
  68. Selkoe DJ. Deciphering the genesis and fate of amyloid ß-protein yields novel therapies for Alzheimer disease. J Clin Invest.. 2002;110:1375-1381.[Medline]
  69. McNeal MC, Zreparsi S, Camicioli R, et al. Predictors of healthy brain aging. J Gerontol Biol Sci.. 2001;56A:B294-B301.[Abstract/Free Full Text]
  70. Blazer DG, Fillenbaum G, Burchett B. The APOE-E4 allele and the risk of functional decline in a community sample of African American and white older adults. J Gerontol Med Sci.. 2001;56A:M785-M789.[Abstract/Free Full Text]
  71. Lovell MA, Xie CS, Markesbery WR. Acrolein is increased in Alzheimer's disease brain and is toxic to primary hippocampal cultures. Neurobiol Aging.. 2001;22:187-194.[Medline]
  72. Rascovsky K, Salmon DP, Ho GJ, et al. Cognitive profiles differ in autopsy-confirmed frontotemporal dementia and AD. Neurology.. 2002;58:1801-1808.[Abstract/Free Full Text]
  73. Holtzman DM, Bales KR, Tenkova T, et al. Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A.. 2000;97:2892-2897.[Abstract/Free Full Text]
  74. Silverberg GD, Levinthal E, Sullivan EV, et al. Assessment of low-flow CSF drainage as a treatment for AD: results of a randomized pilot study. Neurology.. 2002;59:1139-1145.[Abstract/Free Full Text]
  75. Games D, Adams D, Alessandrini R, et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F [beta]-amyloid precursor protein. Nature.. 1995;373:523-527.[Medline]
  76. Hsiao K, Chapman P, Nilsen S, et al. Correlative memory deficits, A beta elevation, and amyloid plaques in transgenic mice. Science.. 1996;274:99-102.[Abstract/Free Full Text]
  77. Sturchler-Pierrat C, Abramowski D, Duke M, et al. Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc Natl Acad Sci U S A.. 1997;94:13287-13292.[Abstract/Free Full Text]
  78. Bales KR, Verina T, Dodel RC, et al. Lack of apolipoprotein E dramatically reduces amyloid [beta]-peptide deposition. Nat Genet.. 1997;17:263-264.[Medline]
  79. Morley JE. The SAMP8 mouse: a model of Alzheimer disease? Biogerontol.. 2002;3:57-60.
  80. Morley JE, Farr SA, Kumar VB, Banks WA. Alzheimer's disease through the eye of a mouse—acceptance lecture for the 2001 Gayle A. Olson and Richard D. Olson prize. Peptides.. 2002;23:589-599.[Medline]
  81. Morley JE, Kumar VB, Barnardo AE, et al. Beta-amyloid precursor polypeptide in SAMP8 mice affects learning and memory. Peptides.. 2000;21:1761-1767.[Medline]
  82. Flood, JF, Morley JE. Learning and memory in the SAMP8 mouse. Neurosci Biobehav Rev.. 1998;22:1-20.[Medline]
  83. Spangler EL, Patel N, Speer D, et al. Passive avoidance and complex maze learning in the senescence accelerated mouse (SAM): age and strain comparisons of SAM P8 and R1. J Gerontol Biol Sci.. 2002;57A:B61-B68.[Abstract/Free Full Text]
  84. Morley JE, Farr SA, Flood JF. Antibody to amyloid beta protein alleviates impaired acquisition, retention, and memory processing in SAMP8 mice. Neurobiol Learn Mem.. 2002;78:125-138.[Medline]
  85. Kumar VB, Farr SA, Flood JF, et al. Site-directed antisense oligonucleotide decreases the expression of amyloid precursor protein and reverses deficits in learning and memory in aged SAMP8 mice. Peptides.. 2000;21:169-1775.
  86. Banks WA, Farr SA, Butt W, Kumar VB, Franko MW, Morley JE. Delivery across the blood-brain barrier of antisense directed against amyloid beta: reversal of learning and memory deficits in mice overexpressing amyloid precursor protein. J Pharmacol Exp Ther.. 2001;297:1113-1121.[Abstract/Free Full Text]
  87. Flood JF, Farr SA, Uezu K, Morley JE. Age-related changes in septal serotonergic, GABAergic and glutamatergic facilitation of retention in SAMP8 mice. Mech Ageing Dev.. 1998;105:173-188.[Medline]
  88. Farr SA, Poon HF, Dogrukol-Ak D, et al. The antioxidants {alpha}-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. J Neurochem. In press.
  89. Hamerman D. Molecular-based therapeutic approaches in treatment of anorexia of aging and cancer cachexia. J Gerontol Med Sci.. 2002;57A:M511-518.[Abstract/Free Full Text]
  90. Morley JE. Decreased food intake with aging. J Gerontol Biol Sci Med Sci.. 2001;56:(Spec Issue 2): 81-88.[Abstract/Free Full Text]
  91. de Castro JM. Age-related changes in the social, psychological, and temporal influences on food intake in free-living, healthy, adult humans. J Gerontol Med Sci.. 2002;57A:M368-M377.[Abstract/Free Full Text]
  92. Morley JE. Dementia is not necessarily a cause of undernutrition. J Am Geriat Soc.. 1996;44:1403-1404.[Medline]
  93. Reynish W, Andrieu S, Nourhashemi F, Vellas B. Nutritional factors and Alzheimer's disease. J Gerontol Med Sci.. 2001;56A:M675-M680.[Abstract/Free Full Text]
  94. Arai Y, Hirose N, Yamamura K, et al. Serum insulin-like growth factor-1 in centenarians: Implications of IG-1 as a rapid turnover protein. J Gerontol Med Sci.. 2001;56A:M79-M82.[Abstract/Free Full Text]
  95. Young KWH, Binns MA, Greenwood CE. Meal delivery practices do not meet needs of Alzheimer patients with increased cognitive and behavioral difficulties in a long-term care facility. J Gerontol Med Sci.. 2001;56A:M656-M661.[Abstract/Free Full Text]
  96. Young KWH, Greenwood CE. Shift in diurnal feeding patterns in nursing home residents for Alzheimer's disease. J Gerontol Med Sci.. 2001;56A:M700-M706.[Abstract/Free Full Text]
  97. Suzuki Y, Critchley HD, Suckling J, et al. Functional magnetic resonance imaging of odor identification: the effect of aging. J Gerontol Med Sci.. 2001;56A:M756-M760.[Abstract/Free Full Text]
  98. Mathey MF, Siebelink E, de Graaf C, van Staveren WA. Flavor enhancement of food improves dietary intake and nutritional status of elderly nursing home residents. J Gerontol Med Sci.. 2001;56A:M200-M205.[Abstract/Free Full Text]
  99. Royall DR, Chiodo LK, Polk MS, Jaramillo CJ. Severe dysosmia is specifically associated with Alzheimer-like memory deficits in nondemented elderly retirees. Neuroepidemiol.. 2002;21:68-73.[Medline]
  100. Simmons SF, Osterweil D, Schnelle JF. Improving food intake in nursing home residents with feeding assistance: a staffing analysis. J Gerontol Med Sci.. 2001;56A:M790-M794.[Abstract/Free Full Text]
  101. Flood JF, Smith GE, Morley JE. Modulation of memory processing by cholecystokinin: dependence on the vagus nerve. Science.. 1987;236:832-834.[Abstract/Free Full Text]
  102. Flood JF, Morley JE. Effects of bombesin and gastrin-releasing peptide on memory processing. Brain Res.. 1988;460:314-322.[Medline]
  103. Flood JF, Merbaum MO, Morley JE. The memory enhancing effects of cholecystokinin octapeptide are dependent on an intact stria terminalis. Neurobiol Learn Mem.. 1995;64:139-145.[Medline]
  104. Flood JF, Garland JS, Morley JE. Evidence that cholecystokinin-enhanced retention is mediated by changes in opioid activity in the amygdala. Brain Res.. 1992;585:94-104.[Medline]
  105. Flood JF, Morley JE. Cholecystokinin receptors mediate enhanced memory retention produced by feeding and gastrointestinal peptides. Peptides.. 1989;10:809-813.[Medline]
  106. Lokk J. News and views on folate and the elderly. J Gerontol Med Sci.. 2003;58A:354-361.
  107. van Asselt DZ, Pasman JW, van Lier JH, et al. Cobalamin supplementation improves cognitive and cerebral function in older, cobalamin-deficient persons. J Gerontol Med Sci.. 2001;56A:M775-M779.[Abstract/Free Full Text]
  108. Kumar VB, Vyas K, Buddhiraju M, Alshaher M, Flood JF, Morley JE. Changes in membrane fatty acids and delta-9 desaturase in senescence accelerated (SAMP8) mouse hippocampus with aging. Life Sci.. 1999;65:1657-1662.[Medline]
  109. Hung MC, Shibasaki K, Yoshida R, Sato M, Imaizumi K. Learning behaviour and cerebral protein kinase C, Antioxidant status, lipid composition in senescence-accelerated mouse: influence of a phosphatidylcholine-vitamin B12 diet. Br J Nutr.. 2001;86:163-171.[Medline]
  110. Roberts SB, Pi-Sunyer X, Kuller L, et al. Physiologic effects of lowering caloric intake in nonhuman primates and nonobese humans. J Gerontol Med Sci.. 2001;56A:(Spec Issue 1): 66-75.[Abstract/Free Full Text]
  111. Allison DB, Miller RA, Austad SN, et al. Genetic variability in responses to caloric restriction in animals and in regulation of metabolism and obesity in humans. J Gerontol Biol Med Sci.. 2001;56A:(Spec Issue 1): 55-65.
  112. Hadley EC, Dutta C, Finkelstein J, et al. Human implications of caloric restriction's effects on aging in laboratory animals: an overview of opportunities for research. J Gerontol Biol Med Sci.. 2001;56A:(Spec Issue 1): 5-6.
  113. Mobbs CV, Bray GA, Atkinson RL, et al. Neuroendocrine and pharmacological manipulations to assess how caloric restriction increases life span. J Gerontol Biol Med Sci.. 2001;56A:(Spec Issue 1): 34-44.
  114. Yehuda S, Rabinovitz S, Carasso RL, Mostofsky DI. The role of polyunsaturated fatty acids in restoring the aging neuronal membrane. Neurol Aging.. 2002;23:843-853.
  115. Idrobo F, Nandy K, Mostofsky DI, Blatt L, Nandy L. Dietary restriction: effects of radial maze learning and lipofuscin pigment deposition in the hippocampus and frontal cortex. Arch Gerontol Geriatr.. 1987;6:355-362.[Medline]
  116. Hajjar I, Schumpert J, Hirth V, Wieland D, Eleazer GP. The impact of the use of statins on the prevalence of dementia and the progression of cognitive impairment. J Gerontol Med Sci.. 2002;57A:M414-M418.[Abstract/Free Full Text]
  117. Aronow WS. Should hypercholesterolemia in older persons be treated to reduce cardiovascular events? J Gerontol Med Sci.. 2002;57A:M411-M413.[Free Full Text]
  118. Aronow WS, Ahn C, Gutstein H. Incidence of new atherothrombotic brain infarction in older persons with prior myocardial infarction and serum low-density lipoprotein cholesterol >=125 mg/dl treated with statins versus no lipid-lowering drug. J Gerontol Med Sci.. 2002;57A:M333-M335.[Abstract/Free Full Text]
  119. Nguyen HT, Black SA, Ray LA, Espino DV, Markides KS. Predictors of decline in MMSE scores among older Mexican Americans. J Gerontol Med Sci.. 2002;57A:M181-M185.[Abstract/Free Full Text]
  120. Morley JE. Diabetes mellitus: a major disease of older persons. J Gerontol Med Sci.. 2000;55A:M255-M256.[Free Full Text]
  121. Meneilly GS, Tessier D. Diabetes in elderly adults. J Gerontol Med Sci.. 2001;56A:M5-M13.
  122. Flood JF, Mooradian AD, Morley JE. Characteristics of learning and memory in streptozocin-induced diabetic mice. Diabetes.. 1990;39:1391-1398.[Abstract]
  123. Morley JE, Flood JF. Psychosocial aspects of diabetes mellitus in older persons. J Am Geriatr Soc.. 1990;38:605-606.[Medline]
  124. Meneilly GS, Cheung E, Tessier D, Yakura C, Tuokko H. The effect of improved glycemic control on cognitive functions in the elderly patient with diabetes. J Gerontol Med Sci.. 1993;48:M117-M121.
  125. Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med.. 1997;336:1216-1222.[Abstract/Free Full Text]
  126. Herholz K, Salmon E, Perani D, et al. Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. Neuroimage.. 2001;17:302-316.
  127. Klunk WE, Bacskai BJ, Mathis CA, et al. Imaging A beta plaques in living transgenic mice with multiphoton microscopy and methoxy-X04, a systemically administered Congo red derivative. J Neuropathol Exp Neurol.. 2002;61:797-805.[Medline]
  128. Buerger K, Zinkowski R, Teipel SJ, et al. Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231. Arch Neurol.. 2002;59:1267-1272.[Abstract/Free Full Text]
  129. Kienzl E, Jellinger K, Jametzky B, Steindl H, Bergmann J. A broader horizon of Alzheimer pathogenesis: ALZAS—an early serum biomarker? J Neural Transm.. 2002;62:(Suppl): 87-95.
  130. Chan DKY. A new hypothesis (concept) of diagnosing Alzheimer's disease. J Gerontol Med Sci.. 2002;57A:M645-M647.[Abstract/Free Full Text]
  131. Grossberg GM, Desai AK. Management of Alzheimer's disease. J Gerontol Med Sci.. 2003;58A:331-353.
  132. Battaglia A, Bruni G, Ardia A, Sacchetti G. Nicergoline in mild to moderate dementia. A multicenter, double-blind, placebo-controlled study. J Am Geriatr Soc.. 1989;37:295-302.[Medline]
  133. Saletu B, Paulus E, Linzmayer L, et al. Nicergoline in senile dementia of Alzheimer type and multi-infarct dementia: a double-blind, placebo-controlled, clinical and EEG/ERP mapping study. Psychopharmacol.. 1995;117:385-395.[Medline]
  134. Olin J, Schneider L, Novit A, Luczak S. Hydergine for dementia. Cochrane Datab Syst Rev.. 2001;2:CD000359.
  135. Waegemans T, Wilsher CR, Danniau A, Ferris SH, Kurz A, Winblad B. Clinical efficacy of piracetam in cognitive impairment: a meta-analysis. Dementia Geriatr Cogn Disord.. 2002;13:217-224.
  136. Fioravanti M, Flicker L. Efficacy of nicergoline in dementia and other age associated forms of cognitive impairment. Cochrane Datab Syst Rev.. 2001;4:CD003159.
  137. Schmitt F, Crager D, Ashford JW, et al. Measuring cognition in advanced Alzheimer's disease for clinical trials. J Neural Transm.. 2002;62:(Suppl): 135-148.
  138. Birmingham K, Frantz S. Set back to Alzheimer vaccine studies. Nat Med.. 2002;8:199-200.[Medline]
  139. Dodel R, Hampel H, Depboylu C, et al. Human antibodies against amyloid beta peptide: a potential treatment for Alzheimer's disease. Ann Neurol.. 2002;52:253-256.[Medline]
  140. Sjogren MJ. Vagal nerve stimulation and cognitive function. J Clin Psychiatr.. 2002;63:972-979.[Medline]
  141. Flaherty JH, Takahashi R, Teoh J, et al. Use of alternative therapies in older outpatients in the United States and Japan: prevalence, reporting patterns, and perceived effectiveness. J Gerontol Med Sci.. 2001;56A:M650-M655.[Abstract/Free Full Text]
  142. Cohen RJ, Ek K, Pan CX. Complementary and alternative medicine (CAM) use by older adults: a comparison of self-report and physician chart documentation. J Gerontol Med Sci.. 2002;57A:M223-M227.[Abstract/Free Full Text]
  143. Honda S, Itoh F, Yoshimoto M, Ohno S, Hinoda Y, Imai K. Association between complement regulatory protein factor H and AM34 antigen, detected in senile plaques. J Gerontol Med Sci.. 2000;55A:M265-M269.[Abstract/Free Full Text]
  144. Fisher A, Morley JE. Antiaging medicine: the good, the bad, and the ugly. J Gerontol Med Sci.. 2002;57A:M636-M639.[Free Full Text]
  145. Loera JA, Black SA, Markides KS, Espino DV, Goodwin JS. The use of herbal medicine by older Mexican Americans. J Gerontol Med Sci.. 2001;56A:M714-M718.[Abstract/Free Full Text]
  146. Andrieu S, Gillette S, Amouyal K, et al. Association of Alzheimer's disease onset with Ginkgo biloba and other symptomatic cognitive treatments in a population of women over 75 years old from the EPIDOS Study. J Gerontol Med Sci.. 2003;58A:372-377.
  147. Wettstein A. Cholinesterase inhibitors and Gingko extracts—are they comparable in the treatment of dementia? Comparison of published placebo-controlled efficacy studies of at least six months' duration. Phytomed.. 2000;6:393-401.
  148. Mix JA, Crews WD. A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract Egb 761 in a sample of cognitively intact older adults: neuropsychological findings. Hum Psychopharmacol.. 2002;17:267-277.[Medline]
  149. Doraiswamy PM, Leon J, Cummings JL, Marin D, Neumann PJ. Prevalence and impact of medical comorbidity in Alzheimer's disease. J Gerontol Med Sci.. 2002;57A:M173-M177.[Abstract/Free Full Text]
  150. Thomas DR, Ashmen W, Morley JE, Evans WJ. Nutritional management in long-term care: Development of a clinical guideline. J Gerontol Med Sci.. 2000;55A:M725-M734.[Abstract/Free Full Text]
  151. Singh MA. Exercise comes of age: rationale and recommendations for a geriatric exercise prescription. J Gerontol Med Sci.. 2002;57A:M262-M282.[Free Full Text]
  152. Drewnowski A, Evans WJ. Nutrition, physical activity, and quality of life in older adults—Introduction. J Gerontol Med Sci.. 2001;56A:(Spec Issue 2): 5.[Free Full Text]
  153. Flaherty JH, Perry HM, Lynchard GS, Morley JE. Polypharmacy and hospitalization among older home care patients. J Gerontol Med Sci.. 2000;55A:M554-M559.
  154. Kamel HK, Phlavan M, Malekgoudarzi B, Gogel P, Morley JE. Utilizing pain assessment scale increases the frequency of diagnosing pain among elderly nursing home residents. J Pain Symptom Manage.. 2001;21:450-455.[Medline]
  155. Michel JP, Pautex S, Zekry D, Zulian G, Gold G. End-of-life care of persons with dementia. J Gerontol Med Sci.. 2002;57A:M640-M644.[Abstract/Free Full Text] King AC, Baumann K, O'Sullivan P, Wilcox S, Castro C. Effects of moderate-intensity exercise on physiological, behavioral, and emotional responses to family caregiving: a randomized controlled trial. J Gerontol Med Sci.. 2002;57A:M26-M36.[Abstract/Free Full Text]
  156. Hebert R, Dubois MF, Wolfson C, Chambers L, Cohen C. Factors associated with long-term institutionalization of older people with dementia: data from the Canadian study of health and aging. J Gerontol Med Sci.. 2001;56A:M693-M699.[Abstract/Free Full Text]
  157. Covinsky KE, Eng C, Lui LY, et al. Reduced employment in caregivers of frail elders: impact of ethnicity, patient clinical characteristics, and caregiver characteristics. J Gerontol Med Sci.. 2001;56A:M707-M713.[Abstract/Free Full Text]
  158. Davis FM, Woolner DF, Frampton C, et al. Prospective, multi-centre trial of mortality following general or spinal anaesthesia for hip fracture surgery in the elderly. Br J Anaesthesia.. 1987;59:1080-1088.[Abstract/Free Full Text]
  159. Ottenbacher KJ, Ostir GV, Peek MK, Goodwin JS, Markides KS. Diabetes mellitus as a risk factor for hip fracture in Mexican American older adults. J Gerontol Med Sci.. 2002;57A:M648-M653.[Abstract/Free Full Text]
  160. Huusko TM, Karppi P, Avikainen V, Kautiainen H, Sulkava R. Randomised, clinically controlled trial of intensive geriatric rehabilitation in patients with hip fracture: subgroup analysis of patients with dementia. Br Med J.. 2000;321:1107-1111.[Abstract/Free Full Text]
  161. Barnes R, Veith R, Okimoto J, Raskind M, Gumbrecht G. Efficacy of antipsychotic medications in behaviorally disturbed dementia patients. Am J Psychiatr.. 1982;139:1170-1174.[Abstract/Free Full Text]
  162. Schneider LS, Pollock VE, Lyness SA. A metaanalysis of controlled trials of neuroleptic treatment in dementia. J Am Geriatr Soc.. 1990;38:553-563.[Medline]
  163. Lonergan E, Luxenberg J, Colford J. Haloperidol for agitation in dementia. Cochrane Datab Syst Rev.. 2002;:CD002852.
  164. Banks MR, Banks WA. The effects of animal-assisted therapy on loneliness in an elderly population in long-term care facilities. J Gerontol Med Sci.. 2002;57A:M428-M432.[Abstract/Free Full Text]
  165. Coleman MT, Looney S, O'Brien J, Ziegler C, Pastorino CA, Turner C. The Eden Alternative: findings after 1 year of implementation. J Gerontol Med Sci. 202;57A:M422–M427.
  166. Morley JE, Flaherty JH. Putting the "home" back in nursing home. J Gerontol Med Sci.. 2002;57A:M419-M421.[Free Full Text]




This Article
Right arrow Full Text (PDF)
Services
Right arrow Download to citation manager
PubMed
Right arrow PubMed Citation

HOME ARCHIVE SEARCH TABLE OF CONTENTS