Rate of MMSE score change in Alzheimer's disease: Influence of education and vascular risk factors

doi:10.1016/j.clineuro.2008.10.006

Clinical Neurology and Neurosurgery

Volume 111, Issue 4, May 2009, Pages 327-330

https://doi.org/10.1016/j.clineuro.2008.10.006 Get rights and content

Abstract

Objective

To test whether higher education accelerates Alzheimer's Disease (AD) progression rate through an effect on the cognitive reserve capabilities of an individual.

Methods

We investigated the influence of schooling and other demographic and clinical conditions (including age, sex, diabetes, arterial hypertension, and acetyl cholinesterase inhibitor – AcheI – therapy) on Mini Mental Status Examination (MMSE) score changes over time in 162 AD patients as well as the interaction of schooling with the above conditions using the Generalized Estimated Equation procedure.

Results

Generalized Estimated Equation procedure yielded an overall progression rate of 0.24 MMSE points per month. Patients with education ≥8 years showed a faster cognitive decline. Male sex, occurrence of arterial hypertension and type II diabetes, and lack of AcheI therapy were associated to faster decline. Stratifying by gender, vascular risk factors, and AcheI therapy, we observed a significant interaction between education and time in the subgroup of patients who had vascular risk factors, and in those who were not treated with AcheI.

Conclusion

These results confirm that schooling may be a significant predictor of cognitive decline as measured by MMSE in persons with AD and provide epidemiological support to “cognitive reserve” model.

Introduction

Alzheimer's disease (AD), is characterized by progressive impairment of cognitive abilities probably depending on both genetic and non-genetic factors. There is evidence suggesting an association between higher education, and faster rate of cognitive decline [1], [2], [3], [4], [5], [6], [7] even if some researchers have reported no such association [8], [9], [10], [11]. The mechanisms underlying such an association are not fully understood. Although it is possible that education is just a surrogate for some other unknown factor, it has also been suggested that education decreases the impact of AD pathology on cognitive function: better educated patients should have higher pathology burden than would have been predicted from their cognitive status, thus experiencing faster decline after disease onset [7]. The “cognitive reserve hypothesis” was supported by functional imaging studies (i.e. SPECT and PET), showing a more pronounced reduction of cerebral blood flow and metabolic rate of glucose utilization in patients with more years of schooling [12], [13].

However, the effect of education on the relationship between pathology burden and cognitive performance is not restricted to AD: individual decline in cognitive performance after brain infarct is higher in subjects with lower educational achievements [14]. On the other hand, vascular risk factors such as arterial hypertension and type II diabetes can contribute to a higher rate of cognitive decline not only increasing the risk of vascular brain injury but also directly affecting amyloid burden [15], [16], [17], [18]. Thus, the interplay between education and vascular risk factors in modulating the progression rate of cognitive decline in AD may be complex and has not been fully explored in epidemiological settings. Furthermore, several previous studies addressing this point relied on autopsy series or on serial MRI examination; thus, the usefulness of anamnestic parameters more readily available in general clinical settings (such as vascular risk factors and years of schooling) in predicting the prognosis of cognitive decline in AD has not been yet investigated. To investigate the role of vascular risk factors, education and their interaction on the progression rate of cognitive decline in AD, we compared the effect of years of schooling on MMSE score changes over time in AD patients with and without vascular risk factors such as arterial hypertension and type II diabetes.

Section snippets

Patients and methods

We retrospectively analyzed data of AD patients included in a longitudinal dataset of consecutive outpatients with dementia established in 2002 in the Department of Neurological and Psychiatric Sciences of the University of Bari, Italy. Dataset included baseline and follow up examinations during which patients and informants were interviewed together to maximize information.

Results

In July 2006 the database included 254 patients diagnosed with probable/possible AD, 162 of whom (121 women and 41 men) satisfied the eligibility criteria (22 had possible AD, 140 had probable AD). Mean (±SD) age at the first visit was 72.2 ± 8.6. Mean follow up was 20.9 ± 8.2 (range 6–39) during which the median number of follow-up visits was 4 (ranged 1–7) Mean MMSE score at baseline was 15.9 ± 5.8 (median 19, range 5–27, but only 22/162 had baseline MMSE score <10), but most patients were in the

Discussion

In this study, schooling, male sex and vascular risk factors were significantly associated to a faster rate of cognitive decline as measured by MMSE in persons with AD. No association was found for older age, whereas AcheI seemed to be associated with a slower rate of cognitive decline as measured by MMSE. It is of note that each association was independent of baseline MMSE, baseline CDR, and the other investigated variables. Overall, our findings were consistent with the results of prior

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Rate of MMSE score change in Alzheimer's disease: Influence of education and vascular risk factors

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Patients and methods

Results

Discussion

Neuroimage

Predicting the rate of cognitive decline in aging and early Alzheimer disease

Neurology

Factors affecting the age of onset and rate of progression of Alzheimer's disease

J Neurol Neurosurg Psychiatry

Rate of progression differs in frontotemporal dementia and Alzheimer disease

Neurology

Education and rate of cognitive decline in incident Alzheimer's disease

J Neurol Neurosurg Psychiatry

Rate of memory decline in AD is related to education and occupation: cognitive reserve?

Neurology

Rates of progression in mild cognitive impairment and early Alzheimer's disease

Neurology

Education modifies the relation of AD pathology to level of cognitive function in older persons

Neurology

Individual trajectories of cognitive decline in patients with dementia of the Alzheimer type

J Clin Exp Neuropsychol

Education provides no protection against Alzheimer's disease

Neurology

Comparison of rate of annual change of mental status score in four independent studies of patients with Alzheimer's disease

Ann Neurol

An autopsy-verified study of the effect of education on degenerative dementia

Brain

Schooling mediates brain reserve in Alzheimer's disease: findings of FDG PET

J Neurol Neurosurg Psychiatry

Education and the cognitive decline associated with MRI-defined brain infarct

Neurology

Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function

Arch Neurol

Hypertension and the rate of cognitive decline in patients with dementia of the Alzheimer type

Alzheimer Dis Assoc Disord

Vascular disease and risk factors, rate of progression, and survival in Alzheimer's disease

J Geriatr Psychiatry Neurol

The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons

JAMA

Diagnostic and statistical manual of mental disorders

Practice parameter: diagnosis of dementia (an evidence-based review). Report of the quality standards subcommittee of the American academy of neurology

Neurology