Amnestic MCI or prodromal Alzheimer's disease?

doi:10.1016/S1474-4422(04)00710-0

The Lancet Neurology

Volume 3, Issue 4, April 2004, Pages 246-248

https://doi.org/10.1016/S1474-4422(04)00710-0 Get rights and content

Summary

The concept of mild cognitive impairment (MCI) draws attention to cognitive changes not severe enough to warrant the diagnosis of dementia. As used today, it covers many pathological disorders and characterises a diverse population of patients who attend memory clinics. Our concern is the underlying heterogeneity. We suggest that it will soon be possible (if it is not already) to identify the underlying pathological disorders before the affected patients meet the criteria of dementia, thanks to specific neuropsychological assessments, neuroimaging, and biomarkers. In particular, patients with Alzheimer's disease (AD), the most important subgroup of patients with MCI, can already be identified before appearance of the fully developed clinical dementia syndrome. Accordingly, this paper proposes diagnostic criteria for “prodromal AD”.

Section snippets

Clinical relevance of the concept of MCI

The concept of MCI draws attention to cognitive disturbances that occur before the clinical diagnosis of dementia. The mild symptomatic phase of AD that precedes the fully developed clinical syndrome of dementia has no official clinical standing. For reasons not fully clarified, but possibly related to regulatory issues, the clinical onset of AD is only when patients meet the criteria for dementia—ie, when they have lost autonomy.⁸ Therefore, MCI characterises many patients at memory clinics

Clinical limitations of MCI

Neuropsychological tests and test scores for the diagnosis of MCI are not fully specified or generally agreed upon. As a consequence, studies of MCI done by different research groups have divergent results (for example, the number of patients with MCI who develop frank dementia of the Alzheimer's type in follow-up studies).3, 9, 10

Our main concern, however, is with the concept of MCI itself and its underlying heterogeneity. As used today, MCI is a syndrome; to have full clinical usefulness, an

What is the disease behind the syndrome?

Although the concept of MCI may be useful in large-scale epidemiological studies, it seems less beneficial when a clinician is facing a patient. In such a situation, the main question that the clinician must address is this: should we label a syndrome or should we try to identify the disease causing the syndrome? To establish, for example, that a person with high body temperature has a fever is only a first step toward the more important definition of the underlying disease, such as tonsillitis

MCI of Alzheimer-type or prodromal AD

By way of example, we comment on one of the subtypes of MCI, the one which leads to AD, because it is now possible to identify AD before the occurrence of the fully developed clinical dementia syndrome,¹⁴ thanks to neuropsychology and newly developed memory tests, neuroimaging, and biomarkers.17, 18

Long before the onset of clinical dementia, AD is already at work on the brain, following a rather predictable route. Neuropathological changes are already present in mesial temporal regions

Conclusion

We have no doubt that, in the future, the diagnosis of the predementia stage of AD will benefit from the combination of neuropsychology and structural and functional neuroimaging, focused on the hippocampal formations and related structures,27, 28, 29, 30 together with measurement of selected biomarkers, such as CSF concentration of the 42 amino-acid residue amyloid-β peptide, tau, and phosphorylated tau protein.31, 32 Such multimodal studies—involving clinical evaluation, neuropsychological

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The discovery of new biomarkers that can distinguish Alzheimer's disease (AD) from mild cognitive impairment (MCI) in the early stages will help to provide new diagnostic and therapeutic strategies and slow the transition from MCI to AD. Patients with AD may present with a concomitant metabolic disorder, such as diabetes, obesity, and dyslipidemia, as a risk factor for AD that may be involved in the onset of both AD pathology and cognitive impairment. Therefore, metabolite profiling, or metabolomics, can be very useful in diagnosing AD, developing new therapeutic targets, and evaluating both the course of treatment and the clinical course of the disease. In addition, studying the relationship between nutritional behavior and AD requires investigation of the role of conditions such as obesity, hypertension, dyslipidemia, and elevated glucose level. Based on this literature review, nutritional recommendations, including weight loss by reducing calorie and cholesterol intake and omega-3 fatty acid supplementation can prevent cognitive decline and dementia in the elderly. The underlying metabolic causes of the pathology and cognitive decline caused by AD and MCI are not well understood. In this review article, metabolomics biomarkers for diagnosis of AD and MCI and metabolic risk factors for cognitive decline in AD were evaluated.
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Personal ViewAmnestic MCI or prodromal Alzheimer's disease?

Summary

Section snippets

Clinical relevance of the concept of MCI

Clinical limitations of MCI

What is the disease behind the syndrome?

MCI of Alzheimer-type or prodromal AD

Conclusion

J Affect Disord

Neurosc Let

Mild cognitive impairment in the elderly: predictor of dementia

Neurology

Definition, course and outcome of mild cognitive impairment

Ageing Neuropsychol Cognition

Mild cognitive impairment: clinical characterization and outcome

Arch Neurol

Senescent forgetfulness: benign and malignant

Can Med Ass J

Age-associated memory impairment: proposed diagnostic criteria and measures of clinical change, report of a National Institute of Mental Health Work Group

Develop Neuropsychol

Ageing-associated decline

Psychogeriatrics

Diagnostic and statistical manual of mental disorders

Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease

Neurology

Classification criteria for mild cognitive impairment: a population-based validation study

Neurology

Incidence and outcome of mild cognitive impairment in a population-based prospective cohort

Neurology

A study of the Lund-Manchester research criteria for frontotemporal dementia: clinical and single-photon emission CT correlations

Neurology

Slowly progressive aphasia without generalized dementia

Ann Neurol

Sensitivity and specificity of three clinical criteria for dementia with Lewy bodies in an autopsy-verified sample

Int J Geriat Psychiatry

Prodromal Alzheimer's disease: a more useful concept than mild cognitive impairment?

Current Opinion in Neurology

Personal View
Amnestic MCI or prodromal Alzheimer's disease?