Inflammation and Alzheimer's disease.

The idea of reserve against brain damage stems from the repeated observation that there does not appear to be a direct relationship between the degree of brain pathology or brain damage and the clinical manifestation of that damage. This paper attempts to develop a coherent theoretical account of reserve. One convenient subdivision of reserve models revolves around whether they envision reserve as a passive process, such as in brain reserve or threshold, or see the brain as actively attempting to cope with or compensate for pathology, as in cognitive reserve. Cognitive reserve may be based on more efficient utilization of brain networks or of enhanced ability to recruit alternate brain networks as needed. A distinction is suggested between reserve, the ability to optimize or maximize normal performance, and compensation, an attempt to maximize performance in the face of brain damage by using brain structures or networks not engaged when the brain is not damaged. Epidemiologic and imaging data that help to develop and support the concept of reserve are presented.

/pdf/what-is-cognitive-reserve-theory-and-research-application-of-4bek0o9s8b.pdf

What is cognitive reserve? Theory and research application of the reserve concept.

Background Cognitive decline complicates early recovery after coronary-artery bypass grafting (CABG) and may be evident in as many as three quarters of patients at the time of discharge from the hospital and a third of patients after six months. We sought to determine the course of cognitive change during the five years after CABG and the effect of perioperative decline on long-term cognitive function. Methods In 261 patients who underwent CABG, neurocognitive tests were performed preoperatively (at base line), before discharge, and six weeks, six months, and five years after CABG surgery. Decline in postoperative function was defined as a drop of 1 SD or more in the scores on tests of any one of four domains of cognitive function. (A reduction of 1 SD represents a decline in function of approximately 20 percent.) Overall neurocognitive status was assessed with a composite cognitive index score representing the sum of the scores for the individual domains. Factors predicting long-term cognitive decline we...

https://www.nejm.org/doi/pdf/10.1056/NEJM200102083440601

Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery.

Background The e4 allele of the apolipoprotein E gene (APOE) is the chief known genetic risk factor for Alzheimer's disease, the most common cause of dementia late in life. To determine the relation between brain responses to tasks requiring memory and the genetic risk of Alzheimer's disease, we performed APOE genotyping and functional magnetic resonance imaging (MRI) of the brain in older persons with intact cognition. Methods We studied 30 subjects (age, 47 to 82 years) who were neurologically normal, of whom 16 were carriers of the APOE e4 allele and 14 were homozygous for the APOE e3 allele. The mean age and level of education were similar in the two groups. Patterns of brain activation during functional MRI scanning were determined while subjects memorized and recalled unrelated pairs of words and while subjects rested between such periods. Memory was reassessed in 14 subjects two years later. Results Both the magnitude and the extent of brain activation during memory-activation tasks in regions affe...

/pdf/patterns-of-brain-activation-in-people-at-risk-for-alzheimer-164a4pgy30.pdf

Patterns of brain activation in people at risk for Alzheimer's disease

OBJECTIVES: To develop a self-report screening tool to identify older people in the emergency department (ED) of a hospital at increased risk of adverse health outcomes, including: death, admission to a nursing home or long-term hospitalization, or a clinically significant decrease in functional status.

DESIGN: Prospective (6-month) follow-up study of a cohort of ED patients aged 65 and older.

SETTING: The EDs of four acute-care hospitals in Montreal, Quebec, Canada.

PARTICIPANTS: Community-dwelling patients aged 65 and older who came to the EDs during the weekday shift over a 3-month recruitment period. Patients were excluded if they could not be interviewed either because of their medical condition or because of cognitive impairment and no other informant was available.

MEASUREMENTS: Measures ascertained at the ED visit included: 27 self-report screening questions on social, physical, and mental risk factors; medical history; use of hospital services, medications, and alcohol; and the Older American Resources and Services (OARS) activities of daily living (ADL) scale. At follow-up, the OARS scale was readministered by telephone, and other adverse health outcomes were ascertained.

RESULTS: Among 1673 patients who completed the follow-up measures, 488 (29.2%) had an adverse health outcome. Scale development and selection methods included logistic regression, receiver operating characteristic curves, and expert judgment. The proposed screening tool (ISAR) comprises six self-report questions on functional dependence (premorbid and acute change), recent hospitalization, impaired memory and vision, and polymedication. The tool performed well in the total cohort aged 65 and older, and in sub-groups defined by disposition (admitted or released from ED), language of questionnaire administration (French or English), information source (patient or other), and other characteristics.

CONCLUSIONS: The ISAR is a short self-report questionnaire that can quickly identify older patients in the ED at increased risk of several adverse health outcomes and those with current disability.

Detection of older people at increased risk of adverse health outcomes after an emergency visit: the ISAR screening tool.

OBJECTIVE This study investigated whether the Apolipoprotein (APOE) epsilon4 allele was associated with cognitive decline in community-dwelling older adults. DESIGN Longitudinal cognitive performance of older adults with the epsilon3/epsilon4 genotype was compared with that of older adults with the epsilon3/epsilon3 genotype. SETTING Aging Clinical Research Center, Stanford University. PARTICIPANTS One hundred community-dwelling older adults were recruited from a pool of 531 individuals who had participated in a memory training study 4 to 5 years earlier. These individuals were concerned about their memory functioning and were recruited through newspaper advertisements and contacts with local senior centers. The 100 individuals who agreed to participate in the follow-up investigation were between 59 and 95 years of age. MEASUREMENTS At both baseline and follow-up, subjects were administered a battery of seven cognitive tests that examined verbal and spatial memory, attention, speed-of-processing, and language abilities. APOE genotype was determined at follow-up. RESULTS Individuals with the epsilon3/epsilon4 APOE genotype were significantly younger than individuals with the APOE epsilon3/epsilon3 genotype. No significant differences were observed between the two groups on measures of attention, speed-of-processing, vocabulary, immediate verbal memory, and immediate spatial memory. However, those older adults with the epsilon3/epsilon4 genotype exhibited significantly greater decline in performance on delayed recall of verbal material than did those with the epsilon3/epsilon3 APOE genotype. CONCLUSION These findings are consistent with previous studies, which suggest that the APOE epsilon4 allele predicts decline on measures of delayed recall.

The APOE ∍4 allele Is Associated with Decline on Delayed Recall Performance in Community-Dwelling Older Adults

We investigated the relationship between basal cortisol and dehydroepiandrosterone (DHEA) levels and impairment in different cognitive and noncognitive measures and the possible interaction of DHEA with hypercortisolemia in dementia in 27 patients diagnosed with Alzheimer's disease (AD). There were 17 men and 10 women. Patients were mildly to moderately cognitively impaired at the time of the initial cortisol measures. Patients were administered the Alzheimer's Disease Assessment Scale (ADAS) and Folstein Mini-Mental State Examination (MMSE) at approximately 6-month intervals. Cortisol and DHEA were determined using conventional 125I radioimmunoassay procedures. Pearson product-moment correlations among cortisol and DHEA measures and both initial and longitudinal clinical measures were calculated. There was a relationship between baseline 8 a.m. cortisol levels and cognitive function at the initial testing as measured by the ADAS cognitive measure, with higher cortisol levels being associated with a greater level of impairment. We did not document a relationship between cortisol or DHEA levels and noncognitive measures. There was a significant correlation between both the initial MMSE and ADAS cognitive measures and initial DHEA level, with lower DHEA levels unexpectedly being associated with better performance on these measures. The initial DHEA levels did not predict decline in cognitive function over time. These findings bring into question the potential usefulness of DHEA as a therapeutic agent.

Cognitive and noncognitive symptoms in dementia patients: relationship to cortisol and dehydroepiandrosterone.

The Apolipoprotein-E (APOE) ɛ4 allele is a risk factor for Alzheimer's disease (AD) and cognitive decline in older adults. Depression may also be a risk factor for dementia, and depression is important in the differential diagnosis of dementia. The authors performed a 5-year longitudinal study of APOE genotype and change in Geriatric Depression Scale scores in 113 community-dwelling older adults. No association was observed between APOE genotype and change in depressive symptoms. These results do not support the hypothesis that the APOE ɛ4 allele is associated with depression. Important objections have been raised to APOE genotyping in the diagnosis of AD. However, the specificity of APOE genotyping in AD diagnosis would not appear to be compromised by an association with depression.

A Longitudinal Study of Apolipoprotein-E Genotype and Depressive Symptoms in Community-Dwelling Older Adults

OBJECTIVE: A classification tree analysis identifies patient groups at varying risk for decline in physical performance 1 year after hospitalization.



DESIGN: Prospective cohort study.



SETTING: Tertiary care VAMC.



PARTICIPANTS: A total of 507 acutely ill hospitalized male veterans aged 65 years and older.



MEASUREMENTS: Eighteen admission characteristics were considered as potential predictors: demographic data, medical diagnoses, functional status (e.g., ADL and IADL), geriatric conditions (e.g., incontinence, vision impairment, weight change), mental status, depression, and physical functioning (measured by self-report (MOS-PFR) and the Physical Performance and Mobility Examination (PPME)). Outcome measure was change in PPME status at 12-months post-admission.



RESULTS: Patients with the greatest risk for decline had both high baseline physical performance (PPME ≥ 9) and at least moderate self-report limitations on physical functioning (MOS-PFR ≤ 36, mean = 30.8). Patients with the lowest risk of decline had impaired baseline physical performance (PPME ≤ 8) but fewer self-report limitations on physical functioning (MOS-PFR ≥ 31, mean = 37.4) and two or less geriatric conditions.



CONCLUSIONS: The predictive role of self-report functioning suggests that perception of the impact of health on one's own physical functioning is associated with future performance. The number of geriatric conditions is also an important predictor of physical performance change. By identifying patient risk groups based on geriatric conditions, physical performance, and self-report physical functioning, future targeting strategies may improve physical performance outcomes for hospitalized older adults.

Maritess Mauricio

Papers

The APOE ∍4 allele Is Associated with Decline on Delayed Recall Performance in Community-Dwelling Older Adults

Cognitive and noncognitive symptoms in dementia patients: relationship to cortisol and dehydroepiandrosterone.

A Longitudinal Study of Apolipoprotein-E Genotype and Depressive Symptoms in Community-Dwelling Older Adults

Identifying hospitalized older patients at varying risk for physical performance decline : A new approach