Mary C. Tierney

Mild Cognitive Impairment

Mild cognitive impairment is a syndrome defined as cognitive decline greater than expected for an individuals age and education level but that does not interfere notably with activities of daily life. Prevalence in population-based epidemiological studies ranges from 3% to 19% in adults older than 65 years. Some people with mild cognitive impairment seem to remain stable or return to normal over time, but more than half progress to dementia within 5 years. Mild cognitive impairment can thus be regarded as a risk state for dementia, and its identification could lead to secondary prevention by controlling risk factors such as systolic hypertension. The amnestic subtype of mild cognitive impairment has a high risk of progression to Alzheimers disease, and it could constitute a prodromal stage of this disorder. Other definitions and subtypes of mild cognitive impairment need to be studied as potential prodromes of Alzheimers disease and other types of dementia.

The NINCDS‐ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer's disease A clinicopathologic study of 57 cases

Neuropathologic confirmation is required to validate the NINCDS-ADRDA Work Group criteria for the clinical diagnosis of Alzheimers disease (AD). Neuropathologic inclusion and exclusion criteria for AD, however, are not uniform. The purpose of this investigation was to examine the confirmation rate for the Work Group criteria against differing neuropathologic criteria for AD. The sample consisted of 57 cases, 22 of which had received a clinical diagnosis of AD. Nine neuropathologic criteria for AD were applied in a blind fashion to each of the 57 cases. Our results indicated that, depending on the neuropathologic criteria applied, the clinicopathologic agreement ranged from 64% to 86%. These findings demonstrate the need for universally accepted neuropathologic and clinical criteria for AD.

Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment.

Fatty acid differences, including docosahexaenoic acid (DHA; 22:6n-3) have been shown in the brains of Alzheimers patients (AD) as compared with normal age-matched individuals. Furthermore, low serum DHA is a significant risk factor for the development of AD. The relative concentration of DHA and other fatty acids, however, in the plasma of AD patients compared with patients with other kinds of dementias (other dementias; OD), patients who are cognitively impaired but nondemented (CIND), or normal patients is not known. In this study we analyzed the total phospholipid, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and lysophosphatidylcholine (lysoPC) fractions of plasma from patients diagnosed with AD, OD, or CIND and compared them with a group of elderly control subjects with normal cognitive functioning. Plasma phospholipid and PC levels of 20:5n-3, DHA, total n-3 fatty acids, and the n-3/n-6 ratio were lower in the AD, OD, and CIND groups. Plasma phospholipid 24:0 was lower in the AD, OD, and CIND groups as compared with the group of control patients, and total n-6 fatty acid levels were higher in the AD and CIND groups only. In the plasma PE fraction, levels of 20:5n-3, DHA, and the total n-3 fatty acid levels were significantly lower in the AD, OD, and CIND groups. DHA levels were lower in the lysoPC fraction of CIND individuals only. There were no other differences in the fatty acid compositions of the different phospholipid fractions. Therefore, in AD, OD, and CIND individuals, low levels of n-3 fatty acids in the plasma may be a risk factor for cognitive impairment and/or dementia. Interestingly, a decreased level of plasma DHA was not limited to the AD patients but appears to be common in cognitive impairment with aging.

Neuropsychological tests accurately predict incident Alzheimer disease after 5 and 10 years

Objective: To determine whether neuropsychological tests accurately predict incident Alzheimer disease (AD) after 5 and 10 years in participants of the Canadian Study of Health and Aging (CSHA) who were initially nondemented. Methods: The CSHA was conducted in three waves: CSHA-1 (1991 to 1992), CSHA-2 (1996 to 1997), and CSHA-3 (2001 to 2002). The 10-year prediction study included those who completed neuropsychological testing at CSHA-1 and received a diagnostic assessment at CSHA-3 (n = 263). The 5-year prediction study included those who completed neuropsychological testing at CSHA-2 and received a diagnostic assessment at CSHA-3 (n = 551). The diagnostic workup for dementia at CSHA-3 was formulated without knowledge of neuropsychological test performance at CSHA-1 or CSHA-2. The authors excluded cases with a baseline diagnosis of dementia or a prior history of any condition likely to affect the brain. Age and education were included in all analyses as covariates. Results: In the 10-year follow-up study, only one test (short delayed verbal recall) emerged from the forward regression analyses. The model with this test and two covariates was significant, χ2 (3) = 31.61, p < 0.0001 (sensitivity = 73%, specificity = 70%). In the 5-year follow-up study, three tests (short delayed verbal recall, animal fluency, and information) emerged from the forward logistic regression analyses. The model was significant, χ2 (5) = 91.34, p < 0.0001 (sensitivity = 74%, specificity = 83%). Both models were supported with bootstrapping estimates. Conclusions: In a large epidemiologic sample of nondemented participants, neuropsychological tests accurately predicted conversion to Alzheimer disease after 5 and 10 years.

Mild Cognitive Impairment: An Operational Definition and Its Conversion Rate to Alzheimer’s Disease

Objective: Because of discrepant findings regarding the accuracy of mild cognitive impairment (MCI) in predicting Alzheimer’s disease (AD), further study of this construct and conversion rates is essential before use in clinical settings. We aimed to develop an operational definition of MCI consistent with criteria proposed by the Mayo Alzheimer’s Disease Center, and to examine its conversion rate to AD. Methods: Patients were identified from an inception cohort of patients with at least a 3-month history of memory problems, and referred to a 2-year university teaching hospital investigation by primary care physicians. We classified 161 nondemented patients at baseline using MCI criteria. Diagnostic workups were completed annually, and patients were classified as meeting criteria for AD or showing no evidence of dementia after 1 and 2 years. Results: Of 161 patients, 35% met MCI criteria at baseline. Conversion rates to AD were 41% after 1 year, and 64% after 2 years. Logistic regression analyses to examine predictive accuracy of MCI after 1 and 2 years, with age and education as covariates, were significant (p < 0.0001). After 1 year, MCI showed an optimal sensitivity of 91% and specificity of 79%, and after 2 years, these values were 88 and 83%, respectively. Conclusions: MCI is an accurate predictor of AD over 1 and 2 years in patients referred by their primary care physicians. Discrepancies in conversion rates may be due to the manner in which patients are recruited to studies as well as the use of different measures to operationalize the construct.

Prediction of transition from cognitive impairment to senile dementia: a prospective, longitudinal study

Objective: The purpose of this investigation was to replicate the statistical approach used in a previous investigation (Toronto study) within a French population to determine the best predictive model for Alzheimers disease (AD).

Mapping the connections between education and dementia.

Explanations for the association between educational attainment and the risk of dementia fall into three main categories. It may arise as an artefact of study methods; education may predict broader socioeconomic circumstances and exposures, or education may reflect brain reserve or cognitive capacity that protect against dementia. Data from the Canadian Study of Health and Aging (N = 6646, giving 44,676 person-years of follow-up) are analyzed to test a series of hypotheses reflecting these explanations. Years of education showed a strong association with the risk of dementia (relative risk [RR] 2.1 for those with less than 6 years of education compared to those with 13 or more years; RR = 2.9 among survivors). Possible artefactual factors were detected, but were insufficient to invalidate the association. Adjustments for a range of other socioeconomic indicators, health problems and lifestyle factors reduced, but did not remove, the association. Adjustments for intelligence and for an indicator of lifetime mental activity also appeared to account for some but not all of the association. The conclusion is that there appears to be a real association between educational attainment and the risk of dementia 50 to 60 years later; this influence appears to run through a number of different, and sometimes complementary, pathways.

Risk Factors for Harm in Cognitively Impaired Seniors Who Live Alone: A Prospective Study

Objectives: To identify risk factors for harm due to self‐neglect or behaviors related to disorientation in cognitively impaired seniors who live alone that can be used in primary care.

Should older adults be screened for dementia

The question of whether to screen for dementia and Alzheimers disease (AD) has been discussed in many forums throughout the world. Generally, medical advisory groups and policy‐making groups have recognized the importance of early diagnosis but have uniformly avoided making recommendations to screen at‐risk populations. This presentation reflects the support for reconsidering the importance of screening individuals at risk or above a certain age. In this statement, the majority of the authors support the consideration of dementia risk factors in individuals at age 50, with routine yearly screening after 75. Other authors remain concerned that the benefits of treatments of early disease do not yet support a general screening recommendation. These statements are made to encourage progress toward the development of a consensus regarding the widespread institution of screening policy. Accordingly, members of the worldwide scientific community are invited to add their perspective by contributing short commentaries (1500 words) on this subject.

Should older adults be screened for dementia? It is important to screen for evidence of dementia!

Multiple arguments for considering routine dementia screening have been presented. Furthermore, dementia diagnoses are widely unrecognized. As a result, persons with dementia are missing important clinical care and treatment interventions. By distinction, the problems of defining, diagnosing, and treating mild cognitive impairment (MCI) are not yet resolved, and MCI is not ready for a screening recommendation. Dementia screening approaches, including cognitive testing and functional assessment, must be evaluated on their scientific merits, including sensitivity and specificity for recognizing affected individuals in at‐risk populations. Screening tests must be “cost‐worthy”, with the benefits of true‐positive test results justifying the costs of testing and resolving false‐positive cases, with due consideration for proper diagnostic evaluation and potential harms. With the tremendous number of new cases projected in the near future and the expected emergence of beneficial therapies, considerably more research is needed to develop more efficient screening systems.