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Clinical Crossroads | Clinician's Corner

A 60-Year-Old Woman With Mild Memory Impairment Review of Mild Cognitive Impairment

James M. Ellison, MD, MPH, Discussant
JAMA. 2008;300(13):1566-1574. doi:10.1001/jama.300.9.jrr80008.
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Many older individuals experience or demonstrate cognitive impairment that is significantly abnormal for their age and education yet beneath the threshold for a diagnosis of dementia. This mild cognitive impairment causes minimal functional impairment and is often overlooked in clinical settings, yet affected individuals are at heightened risk for a range of adverse outcomes including conversion to dementia. The case of Ms E, a 60-year-old woman with mild memory impairment and white matter lesions on magnetic resonance imaging, provides an opportunity to consider the questions that face patient, family, and clinicians when mild cognitive symptoms prompt a search for diagnosis and management options. Discussion of her case reviews mild cognitive impairment with emphasis on an evidence-based approach to evaluation and treatment, including management of comorbid medical conditions, lifestyle changes, and pharmacotherapy.

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Figure. T2-Weighted Fluid-Attenuated Inversion Recovery Magnetic Resonance Image of Ms E's Brain
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Clinical and Ethical Response to the Case of "A 60-Year-Old Woman With Mild Memory Impairment
Posted on September 24, 2008
J.S. Swindell Ph.D. and Joseph S. Kass M.D., J.D., Ph.D., M.D., J.D.
Baylor College of Medicine
Conflict of Interest: None Declared
We would like to comment on the case of "A 60-Year-Old Woman With Mild Memory Impairment" from both a clinical and an ethical perspective, because in this case the issues are inextricably intertwined. Mild cognitive impairment (MCI) is an abnormal process that is thought to represent the earliest clinically apparent transition from normal aging to dementia.(1) While normal elderly may feel that their memory is not as sharp as it was when they were younger, they are able to maintain a level of cognitive function relatively unchanged from their baseline. On cognitive testing they perform in line with their age cohort. Patients with MCI report a decline from their cognitive baseline and have evidence of difficulty in one or more cognitive domains on cognitive testing.(2) Ms E initially presented with an isolated memory complaint suggestive of amnestic MCI. However, subsequent testing a year later demonstrated both a subjective and objective decline from baseline involving multiple cognitive domains. Approximately 10%-15% of patients with MCI progress to dementia annually (with about 40%-80% of patients progressing to Alzheimer's disease within 5 years),(3) and this is likely Ms E's prognosis.
Although Ms E's history and examination suggest the diagnosis of MCI, further work-up is warranted. Common co-morbidities that may adversely affect cognitive function include depression, kidney and liver disease, basic electrolyte abnormalities, vitamin B12 deficiency, thyroid function and when appropriate syphilis. Structural imaging of the brain with either an unenhanced CT or MRI is also important. Such imaging may reveal extensive cerebrovascular disease, a chronic subdural hematoma, normal pressure hydrocephalus, or a neoplasm that may be the cause of the patient's cognitive decline. Additionally, this imaging may suggest a pattern of cerebral atrophy such as hippocampal atrophy that suggests a higher risk of progression to a neurodegenerative dementia. (4)
We recommend that Ms E's physicians:
(a) Consider ordering more extensive neuropsychological testing to qualify and quantify the cognitive impairment. Having this baseline may improve identification of Ms E's potential progression to dementia if follow-up testing is performed. Also, neuropsychological testing may aid the physician in categorizing the type of MCI pattern: amnestic single domain or multi-domain or non-amnestic single domain or multi-domain. These characterizations may have implications for the type and risk of dementia progression.(5,6) Furthermore, this testing may untangle the impact of depression on a patient's cognitive decline.(7)
(b) Consider prescribing her donepezil. Although there is no FDA approved medication for MCI, the Alzheimer's Disease Cooperative Study looked at the effect of Vitamin E and donepezil on progression from amnestic MCI to dementia, and the authors felt that individualized counseling about the medication would be appropriate. (8)
(c) Optimize management of vascular risk factors, given (i) the burden of cerebrovascular disease seen on her brain MRI, and (ii) epidemiological studies suggest an association between these risk factors and cognitive impairment.(9)
(d) Encourage Ms E to engage in social activities as much as possible, engage in both physical and mental exercises, and keep a diet rich in fruits, vegetables, and foods that contain omega-3 fatty acids because non-pharmocological interventions are important too. A number of longitudinal studies of normal elderly have demonstrated the positive effects of physical activity and intellectual stimulation on preserving cognitive function.(10)
(e) Strive to optimize treatment of Ms E's depression.
(f) Help Ms E talk with her family members to develop a support plan in the event that her condition worsens. This conversation should include plans for where she will live should her condition decline, and necessary legal and financial arrangements should be made.
(g) Have Ms E draft an advance directive and communicate to her family her values and preferences regarding medical care during the various stages of dementia. This will prevent future conflicts among her family members and extend patient autonomy.
(h) Put Ms E in contact with her local Alzheimer's Association to find an early-stage support group.
We thank Ms E for sharing her story with us.
1. Peterson RC, Morris JC. Mild cognitive impairment as a clinical entity and treatment target. Arch Neurol. 2005; 1160-1163.
2. Nelson AP, O'Connor MG. Mild cognitive impairment: a neuropsychological perspective. CNS Spectr. 2008;13(1):56-64.
3. Peterson RC, Thomas RG, Grudman M et al. Vitamin E and donepezil in the treatment of mild cognitive impairment. N Engl J Med 2005; 352: 2379-2388.
4. Jack CR Jr, Shiung MM, Weigand SD et al. Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI. Neurology 2005 65:1227-1231.
5. Peterson RC, Negash S. Mild cognitive impairment: an overview. CNS Spectr. 2008 13(1):45-53.
6. Palmer K, Backman L, Winblad B et al. Mild cognitive impairment in the general population: occurrence and progression to Alzheimer disease. Am J Geriatr Psychiatry 2008; 16:603-611.
7. Nelson AP, O'Connor MG. Mild cognitive impairment: a neuropsychological perspective. CNS Spectr. 2008;13(1):56-64.
8. Peterson RC, Thomas RG, Grudman M et al. Vitamin E and donepezil in the treatment of mild cognitive impairment. N Engl J Med 2005; 352: 2379-2388.
9. Yaffe K., Kanaya A., Lindquist K, et al. The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA 2004;292:2237-42.
10. Chertkow H, Massoud F, Nasreddine Z et al. Diagnosis and treatment of dementia: 3. Mild cognitive impairment and cognitive impairment without dementia. CMAJ 2008;178(10):1273-85.
*No relevant financial interests*
A 60-year-old Woman with Multiple Domain Amnestic Vascular Cognitive Impairment
Posted on September 17, 2008
Rufus O Akinyemi, MBBS, MSc, FMCP
Institute for Ageing and Health, Newcastle University,Newcastle upon Tyne, UK.
Conflict of Interest: None Declared
In my opinion, 60-year- old Ms E has a multiple domain amnestic mild cognitive impairment (MCI) of probable vascular origin[1]. The history of memory loss, cognitive assessment findings of significant memory deficits and executive dysfunction, her late-onset depression, MRI features of sub-cortical and periventricular white matter lesions, dyslipidaemia, apoe3/e4 genotype, and positive ANA with speckling, all point to a small vessel disease (possibly an autoimmune microangiopathy) as the aetiology of this vascular cognitive impairment. Small vessel diseases currently account for up to 25% of cases of VCI with lesions ranging from lacunes, microinfarcts, demyelination, gliosis and microangiopathic changes[2]. Progression to full blown vascular dementia may depend on how well the predisposing risks are managed. Distinguishing MCI from normal cognitive aging may be difficult because of lack of precise knowledge of cognitive changes in normal aging[3]. However, historical details coupled with neuropsychological assessment may help when the subject's performance is worse compared to population- derived normative data, although this may be contaminated. Neuroimaging including volumetric assessment of medial temporal lobe, hippocampus and entorhinal cortex is valuable,[4,5] while use of biomarkers including CSF measures of B amyloid and tau is still in its infancy[6]. The checklist for cognitive decline in an older adult will include degenerative (AD, FTD, PD, CBD), vascular, traumatic (TBI, SDH), psychiatric, medical illness-related (heart failure, chronic kidney disease, liver disease) or nutrition-related conditions(Vit B12 deficiency). Detailed history, mental state and neurological examination, relevant laboratory investigations, neuropsychological assessment and neuroimaging will help in teasing out the differentials. The literature[7,8] suggests a possible role of diet in age-related cognitive decline, and cognitive impairment of both degenerative (AD) or vascular origin. The typical Mediterranean diet, high monounsaturated fatty acids energy intake has been associated with protection against cognitive decline. Also, fish consumption and cereals reduce the prevalence of AD in European and North American countries. Aluminium-containing additives or aluminium from drinking water and vitamin deficiencies, especially vitamin B6, B12 and folates, and antioxidant deficiencies (vitamins E and C) could also influence the memory capabilities and have an effect on cognitive decline. Living with others appears to be protective against cognitive decline, and donepezil may be useful in vascular MCI[9]. Concerns about driving, employment, financial issues and residential arrangements need individualized and multi-party discussions including the patient, family/care givers and the health care professional. Necessary adjustments in any of these functional activities will be determined by the nature and degree of impairment in cognition and other faculties, with alternatives adequately provided for.
For Ms E, it is necessary to adequately establish her diagnosis, the aetiology and the predisposing conditions. This provides the template for appropriate intervention to, at least, slow down the progression of her dementing illness. Her manifest helplessness and fear of the unknown require appropriate psychosocial intervention including techniques such as reality orientation. This will improve her sense of control and self- esteem. Anti-lipidaemic agents may be useful; and in the light of the recently published Cache County study[10] showing better cognitive performance in elderly subjects taking antioxidant vitamins E and C supplements in combination with nonsteroidal anti-inflammatory drugs, I will recommend these for Ms E in addition to managing any other risk factors identified.
1.Petersen RC. Mild cognitive impairment as a diagnostic entity. Journal of Internal Medicine 2004; 256: 183 – 194.
2. Roman GC, Erkinjuntti T, Wallin A, Pantoni L, Chui HC. Subcortical ischaemic vascular dementia. Lancet Neurol 2002; 1: 426 – 436.
3.Ivnik RJ, Smith GE, Lucas JA, et al. Testing normal older people three or four times at 1- to 2-year intervals: Defining normal variance. Neuropsychology 1999; 13: 121 – 127.
4.Jack CR Jr, Petersen RC, Xu YC, et al. Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease. Neurology 1997; 49: 786 – 794.
5.Xu Y, Jack CR, Jr., O'Brien PC, et al. Usefulness of MRI measures of entorhinal cortex versus hippocampus in AD. Neurology 2000; 54: 1760 – 1767.
6.Growdon JH. Biomarkers of Alzheimer disease. Arch Neurol 1999; 56: 281 - 283.
7.Panza F, Solfrizzi V, Colacicco AM, et al. Mediterranean diet and cognitive decline. Public Health Nutr. 2004; 7 (7); 959 – 963.
8.Solfrizzi V, Panza F, Caparso A. The role of diet in cognitive decline. J Neural Transm. 2003; 110(1): 95 -110.
9.Malouf R, Birks J. Donepezil for vascular cognitive impairment. Cochrane Database Syst Rev. 2004; (1): CD004395.
10.Fotuhi M, Zandi PP, Hayden KM, et al. Better cognitive performance in elderly taking antioxidant vitamins E and C supplements in combination with nonsteroidal anti-inflammatory drugs: the Cache County Study. Alzheimers Dement. 2008 May; 4(3):223-227.
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