Aging and Memory

by Dr. Lucy Nurek

One of the key concerns of older adults is the experience of memory loss. A frequent complaint of older adults is that thoughts are fleeting - they cannot revive information that was active only a second ago.(1)  For example, they have a thought as someone is speaking but cannot "pick up" the thought by the end of the speaker's sentence; or they cannot remember why they came into the kitchen.(1)

Older adults are slower to refresh words, in comparison to younger adults. Furthermore, older adults show intact perceptual processing but in contrast tere is an age-related deficit in the simple reflective operation of thinking of just-presented item (refreshing).(1) Impairment in such a process potentially has a wide-ranging impact on all higher-order cognition.(1-3) For most of the older adults, memory performance depends on the time of day, with performance being optimal early in the morning and declining during the late afternoon hours.(4)

Mild cognitive impairment a risk for dementia

Mild cognitive impairment (MCI) os defined as cognitive defects that do not interfere with daily living. It may include slower thinking, a reduced ability to learn, and impaired memory. People with MCI are at increased risk for deeveloping dementia or Alzheimer's disease (AD) when compared with similarly aged individuals in the general population.(5)

Dementia refers to a group of illnesses that involve memory, behavior, learning and communicating problems. The problems are progressive, which means they slowly get worse. The two major causes of non-reversible, degenerative dementia are vascular dementia (loss of brain function due to a series of small strokes) and Alzheimer's disease.

The two conditions often occur together. The pathophysiology of Alzheimer's disease is complex and involves several different biochemical pathways.(6) There is evidence that memory and cognitive disturbances results from reduced cholinergic transmission (related to neurotransmitter acetyl-choline). Wide-range evidence shows degeneration of the cholinergic projections in patients with Alzheimer's disease, as well as loss of cholinergic cell bodies and a reduction of the enzymes involved. Dementia in AD, that affects approximately 4.5 million people in the United States, results from progressive synaptic loss and neuronal death.(7)

Mild cognitive impairment represents a transitional state between the cognitive changes of normal aging and very early dementia and is becoming increasingly recognized as a risk factor for Alzheimer's disease.(8) Physical changes that occur in the aging brain and factors like chronic inflammation, vascular diseases, and even stress, are implicated in mild cognitive impairment.

How does aging change the brain?

Improved technology, like higher resolution magnetic resnonance imaging (MRI) and positron emission tomography (PET) scans, changed the way scientists view the aging brain. It was long known that from early adulthood onward, brain weight and volume decline. On average, the brain loses 5 to 10 percent of its weight between the ages of 20 and 90.

It was previously thought that this loss was caused by the loss of nerve cells (neurons). Now it is clear that if you don't have a specific disease that causes loss of nerve cells, the number of neurons does not decrease much with age. Nevertheless, the number of synaptic contacts between neurons declines.(9) New research suggests that brain aging and cognitive decline, like age-related memory loss, are related to chemical changes in the brain. (10-13)

The physical changes associated with the aging brain include:

Reduction of the elevations (gyri) on the surface of the brain, and widenint of the grooves (sulci) on the surface

Significant changes in white matter microstructure, most prominently in anterior (frontal) brain regions (14-16)

Increased formation of the "senile plaques," or abnormally hard clusters of damaged or dying neurons (17-19)

Increased number of the "neurofibrillary tangles," or insoluble twisted fibers that are found inside of the brains cells (19-21)

One of the basic mental acts is refreshing - briefly thinking of something just after it is no longer present. Using functoinal magnetic resonance imaging (MRI), researchers found that relative to young adults, older adults showed reduced refresh-related activity in some areas of the prefrontal cortex (let middle frontal gyrus), but not in the other refresh-related areas.(22) This provides strong evidence that a frontal component of the circuit that subserves this basic cognitive process is especially vulnerable to aging.(23) Researchers also found that presenting emotional information disrupted an anterior component of the refresh circuit.(24)

There is also evidence that brain regions associated with emotional processes deteriorate less with age than many other regions. In aging people without dementia, the significant reductions are noticeable in the volume of corpus callosum (bundle of nerve fibers connecting left and right hemispheres) with a front-to-back gradient.(25) In contrast, individuals with dementia and Alzheimer's disease show substantial reduction in volume of hippocampus (a region involved with conversion of short-term to long-term memories and the emotional states).(26)

Average life expectancy and the maximum life span

While there are genetic diseases of premature aging, there are no diseases causing immortality. Although many people today have lived past 100, none have lived to be 200. Chances for death are decreased by improvements in general living conditions.(27) As a result, during the last two millennia, average life expectancy has risen from 30 years in ancient Rome to almost 80 years today in the developed countries.(27) The inborn aging process in developed countries limits human average life expectancy at birth (a rough measure of the healthy life span) to about 85 years. (28) Few people live past 100 years, and only one is known to have lived to 122 years of age.*

Supporting Research

1. Johnson MK, et al. Second thoughts versus second looks: An age-related deficit in reflectively refreshing just-sctivated information. Psychological Science 2002;13:64-67

2. Johnson MK, et al. An Age-Related Deficit in Prefrontal Cortical Function Associated with Refreshing Information. Psychological Science 2004;15:2, 127-132

3. Johnson MK, et al. Using fMRI to investigate a component process of reflection: prefrontal correlates of refreshing a just-activated representation. Cogn Affect Behav Neurosci 2005 Sep;5(3):339-61 13(1),68-71

4. Ryan L, et al. Caffeine Reduces Time-of-Day Effects on Memory Performance in Older Adults. Psychological Science 2002; 13 (1), 68-71

5. Grundman M et al. Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials. Arch Neurol. 2004 Jan;61(1):59-66

6. Bozoki A et al. Mild cognitive impairments predict dementia in nondemented elderly patients with memory loss. Arch Neurol. 2001 Mar;58(3):411-6

7. Petersen RC et al. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the 14 Quality Standards Subcommittee of the
American Academy of Neurology. Neurology. 2001 May 8;56(9):1133-42

8. Morris JC et al. Mild cognitive impairment represents early-stage Alzheimer disease. Arch Neurol. 2001 Mar;58(3):397-405

9. Doraiswamy PM. Non-cholinergic strategies for treating and preventing Alzheimer's disease. CNS Drugs. 2002;16(12):811-24

10. Lleo A et al. Current pharmacotherapy for Alzheimer's disease. Annu Rev Med. 2006;57:513-33

11. Battaini F & Pascale A. Protein kinase C signal transduction regulation in physiological and pathological aging. Ann N Y Acad Sci. 2005 Dec;1057:177-92.

12. Racchi M et al. Dehydroepiandrosterone and the relationship with aging and memory: a possible link with protein kinase C functional machinery. Brain Res Brain Res Rev. 2001 Nov;37(1-3):287-93.

13. Racchi M et al. Dehydroepiandrosterone (DHEA) and the aging brain: flipping a coin in the "fountain of youth". CNS Drug Rev. 2003 Spring;9(1):21-40.

14. Head D et al. Differential vulnerability of anterior white matter in nondemented aging with minimal celeration in dementia of the Alzheimer type: evidence from diffusion tensor imaging. Cereb Cortex. 2004 Apr;14(4):410-23

15. Head D et al. Frontal-hippocampal double dissociation between normal aging and Alzheimer's disease. Cereb Cortex. 2005 Jun;15(6):732-9

16. Pfefferbaum A et al. Frontal circuitry degradation
marks healthy adult aging: Evidence from diffusion tensor imaging. Neuroimage. 2005 Jul 1;26(3):891-9

17. Giannakopoulos P et al. Cerebral cortex pathology in aging and Alzheimer's disease: a quantitative survey of large hospital-based geriatric and psychiatric cohorts. Brain Res Brain Res Rev. 1997 Oct;25(2):217-45

18. Hof PR et al. The neuropathological changes
associated with normal brain aging. Histol Histopathol. 1996 Oct;11(4):1075-88.

19. Knopman DS et all. Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol. 2003
Nov;62(11):1087-95

20. Harman D. Aging: overview. Ann N Y Acad Sci. 2001 Apr; 928:1-21

21. Trubiani O et al. Melatonin provokes cell
death in human B-lymphoma cells by mitochondrial-
dependent apoptotic pathway activation. Journal of Pineal Research 2005 Nov;39 (4):425-431.

22. Carrillo-Vico A et al. Evidence of melatonin synthesis by human lymphocytes and its physiological
significance: possible role as intracrine, autocrine, and/or paracrine substance. FASEB J. 2004 Mar;18(3):537-9

23. Lardone PJ. Et al. Melatonin synthesized by Jurkat human leukemic T cell line is implicated in IL-2 production. J Cell Physiol. 2006 Jan;206(1):273-9

24. Jou MJ et al. Visualization of the antioxidative effects of melatonin at the mitochondrial level during oxidative stress-induced apoptosis of rat brain astrocytes. J Pineal Res. 2004 Aug;37(1):55-70

25. Reiter, R. et al Pharmacological utility of melatonin in reducing oxidative cellular and molecular damage. Pol J Pharmacol. 2004 Mar-Apr;56(2):159-70

26. Reiter, R. et al. Melatonin in the context of the free radical theory of aging: Ann NY Acad Sci 1996;786: 362-78

27. Harman D., Aging: overview, Ann N Y Acad Sci 2001:Apr;928:1-21

28. Harman, D. Free radical theory of aging: an update: increasing the functional life span. Ann N Y Acad Sci. 2006 May;1067:10-21

* The oldest documented person, Jeanne Louise Calment, was born in Arles, France, on February 21, 1875. She died at 122 years on August 4, 1997. She rode a bicycle to the age of 100.