Simona Sacuiu

Secular changes in cognitive predictors of dementia and mortality in 70-year-olds

Background: Successive elderly birth cohorts improved in cognitive performance during the 20th century. It is not clear whether this influences cognitive predictors of dementia and mortality. Objective: In 2 longitudinal population studies, representing 2 cohorts of 70-year-olds examined 30 years apart, we investigated the relation between baseline cognitive function and 5-year occurrence of dementia and mortality. Methods: Two representative cohorts of 70-year-olds initially free from dementia born in 1901–1902 (cohort 1901–1902: n = 381) and 1930 (cohort 1930: n = 551) from Gothenburg, Sweden, were examined in 1971–1972 and 2000–2001 and after 5 years for the outcome of dementia and death. Recent memory was evaluated during psychiatric examinations, and nonmemory domains using psychometric tests. Results: At age 70, cohort 1930 performed better on psychometric tests, and had fewer recent memory problems compared to cohort 1901–1902. During 5-year follow-up, 5.0% in cohort 1901–1902 and 4.4% in cohort 1930 (p = 0.742) developed dementia, and 15.7% in cohort 1901–1902 and 4.4% in cohort 1930 died (p < 0.001). Recent memory was associated with incident dementia in both cohorts. Low scores in nonmemory tests were associated with incident dementia in cohort 1901–1902, but not in cohort 1930. Recent memory problems and lower scores in nonmemory tests were associated with 5-year mortality in cohort 1901–1902, but not in cohort 1930. Conclusions: Secular changes in cognitive performance may influence cognitive predictors of dementia and mortality, despite similar incidence of dementia. The findings should be taken cautiously due to differences between cohorts in refusal rates, quality of education, and dementia recognition in medical records.

Onset and rate of cognitive change before dementia diagnosis: findings from two Swedish population-based longitudinal studies.

We used data from two population-based longitudinal studies to estimate time of onset and rate of accelerated decline across cognitive domains before dementia diagnosis. The H70 includes an age-homogeneous sample (127 cases and 255 non-cases) initially assessed at age 70 with 12 follow-ups over 30 years. The Kungsholmen Project (KP) includes an age-heterogeneous sample (279 cases and 562 non-cases), with an average age of 82 years at initial assessment, and 4 follow-ups spanning 13 years. We fit mixed linear models to the data and determined placement of change points by a profile likelihood method. Results demonstrated onset of accelerated decline for fluid (speed, memory) versus crystallized (verbal, clock reading) abilities occurring approximately 10 and 5 years before diagnosis, respectively. Although decline before change points was greater for fluid abilities, acceleration was more pronounced for crystallized abilities after the change points. This suggests that onset and rate of acceleration vary systematically along the fluid-crystallized ability continuum. There is early onset in fluid abilities, but these changes are difficult to detect due to substantial age-related decline. Onset occurred later and acceleration was greater in crystallized abilities, suggesting that those markers may provide more valid identification of cases in later stages of the prodromal phase.

Nonlinear blood pressure effects on cognition in old age: separating between-person and within-person associations.

Midlife hypertension is associated with increased risk of cognitive impairment in later life. The association between blood pressure (BP) in older ages and cognition is less clear. In this study we provide estimates of between-person and within-person associations of BP and cognition in a population-based sample (N = 382) followed from age 70 across 12 occasions over 30 years. Between-person associations refer to how individual differences in BP relates to individual differences in cognition. Within-person associations refer to how individual and time specific changes in BP relate to variation in cognition. Hierarchical linear models were fitted to data from three cognitive measurements (verbal ability, spatial ability, and perceptual speed) while accounting for demographic and health-related covariates. We found consistent nonlinear between-person associations between diastolic BP (DBP) and cognition, such that both low (<75 mmHg) and high (>95 mmHg) pressure were associated with poorer cognition. Within-person decreases in systolic BP (SBP) and DBP were associated with decreases in perceptual speed. Notably, between-person and within-person estimates did not reveal similar associations, suggesting the need to separate the two effects in the analysis of associations between BP and cognition in old age.

A population-based study on the influence of brain atrophy on 20-year survival after age 85

Background: Individuals aged 80 years and older is the fastest growing segment of the population worldwide. To understand the biology behind increasing longevity, it is important to examine factors related to survival in this age group. The relationship between brain atrophy and survival after age 85 remains unclear. Methods: A population-based sample (n = 239) had head CT scans at age 85 and was then followed until death. Cortical atrophy and ventricular size were assessed. Statistical analyses included Cox proportional hazards models with time to death as the outcome and considering a large number of possible confounders, including baseline cognitive function, incident dementia, and somatic disorders. Results: Mean survival time (±SD) was 5.0 ± 3.6 years (range 0.10–19.8 years). Decreased survival was associated with temporal, and frontal atrophy, sylvian fissure width and a number of ventricular measures after adjustment for potential confounders. In participants without dementia at baseline (n = 135), decreased survival was associated with temporal lobe atrophy and bifrontal ratio. In those with dementia (n = 104), decreased survival was associated with third ventricle width, cella media ratio, and ventricle-to-brain and ventricle-to-cranial ratio. Conclusions: Several indices of brain atrophy were related to decreased survival after age 85, regardless of dementia status. Brain atrophy is rarely mentioned as a significant indicator of survival in the elderly, independent of traditional predictors such as cardiovascular disease or cancer. The biology behind the influence of brain atrophy on survival needs to be further scrutinized.

Modifiable risk factors for prevention of dementia in midlife, late life and the oldest-old: Validation of the LIBRA index

BACKGROUND Recently, the LIfestyle for BRAin health (LIBRA) index was developed to assess an individuals prevention potential for dementia. OBJECTIVE We investigated the predictive validity of the LIBRA index for incident dementia in midlife, late life, and the oldest-old. METHODS 9,387 non-demented individuals were recruited from the European population-based DESCRIPA study. An individuals LIBRA index was calculated solely based on modifiable risk factors: depression, diabetes, physical activity, hypertension, obesity, smoking, hypercholesterolemia, coronary heart disease, and mild/moderate alcohol use. Cox regression was used to test the predictive validity of LIBRA for dementia at follow-up (mean 7.2 y, range 1-16). RESULTS In midlife (55-69 y, n = 3,256) and late life (70-79 y, n = 4,320), the risk for dementia increased with higher LIBRA scores. Individuals in the intermediate- and high-risk groups had a higher risk of dementia than those in the low-risk group. In the oldest-old (80-97 y, n = 1,811), higher LIBRA scores did not increase the risk for dementia. CONCLUSION LIBRA might be a useful tool to identify individuals for primary prevention interventions of dementia in midlife, and maybe in late life, but not in the oldest-old.

The prevalence of psychotic symptoms and paranoid ideation in non-demented population samples aged 70–82 years

Recent populationQ3 studies have reported an approximate 10% prevalence of psychotic symptoms among elderly aged 85 years and older. Psychotic symptoms may be less prevalent among younger elderly. We examined the prevalence of psychotic symptoms in a population‐based sample of non‐demented elderly aged 70–82 years.

Cognitive Function in Older Suicide Attempters and a Population-Based Comparison Group

Objective: The aim was to compare cognitive function in older suicide attempters with a population-based comparison group. Methods: Hospitalized suicide attempters aged 70 years and older were assessed cognitively at baseline (n = 99) and 1-year follow-up (n = 59). Depression symptoms were rated with the Montgomery-Åsberg Depression Rating Scale (MADRS). Results of cognitive assessments in attempters were compared with results in nonattempter comparison subjects (n = 115) selected among participants in our population-based health studies to yield a similar distribution of MADRS scores. Results: Suicide attempters scored lower on Mini-Mental State Examination (MMSE) than comparison persons. Among attempters, the mean MMSE score was lower in those with medically serious attempts. Attempters displayed poorer performance on tests of pentagon drawing and abstract thinking compared to comparison persons, and the results remained also after exclusion of those with medically serious attempts. At 1-year follow-up, significant improvement in MADRS scores was observed in the attempters. No evidence of improvement could be shown regarding cognitive deficits. Conclusion: Older suicide attempters may have cognitive deficits, which may in part be related to the attempt itself. This needs to be taken into account when designing intervention strategies.

Cortical Atrophy is Associated with Accelerated Cognitive Decline in Mild Cognitive Impairment with Subsyndromal Depression

OBJECTIVES To investigate the association between cognitive decline and cortical atrophy in individuals with mild cognitive impairment (MCI) and chronic subsyndromal symptoms of depression (SSD) over a 4-year period. DESIGN Prospective cohort study. SETTING Multicenter, clinic-based. PARTICIPANTS Within the Alzheimers Disease Neuroimaging Initiative repository, the Neuropsychiatric Inventory was used to identify individuals with MCI and stable endorsement (SSD group N = 32) or no endorsement (non-SSD group N = 69) of depressive symptoms across time points. MEASUREMENTS Repeated measures of cognitive outcomes, cortical atrophy, and their associations were evaluated with mixed effects models adjusting for age, education, sex, and APOE genotype. RESULTS The SSD group demonstrated accelerated decline on measures of global cognition (Alzheimer Disease Assessment Scale; df = 421, t = 2.242, p = 0.025), memory (Wechsler Memory Scale-Revised Logical Memory II; df = 244, t = -2.525, p = 0.011), information processing speed (Trail Making Test Parts A [df = 421, t = 2.376, p = 0.018] and B [df = 421, t = 2.533, p = 0.012]), and semantic fluency (Category Fluency; df = 424, t = -2.418, p = 0.016), as well as accelerated frontal lobe (df = 341, t = -2.648, p = 0.008) and anterior cingulate (df = 341, t = -3.786, p < 0.001) atrophy. No group differences were observed for rate of decline on measures of attention, learning, and confrontation naming or for rate of atrophy in any other regions. Accelerated frontal lobe and anterior cingulate atrophy was associated with cognitive decline on measures of global cognition, information processing speed, and semantic fluency (all p < 0.05), but not memory. CONCLUSIONS Individuals with chronic SSD may represent an MCI subgroup that is highly vulnerable to accelerated cognitive decline, an effect that may be governed by frontal lobe and anterior cingulate atrophy.

Longitudinal evaluation of criteria for subjective cognitive decline and preclinical Alzheimer's disease in a memory clinic sample

Subjective cognitive decline (SCD) and biomarker‐based “at‐risk” concepts such as “preclinical” Alzheimers disease (AD) have been developed to predict AD dementia before objective cognitive impairment is detectable. We longitudinally evaluated cognitive outcome when using these classifications.

High Prevalence of Stress and Low Prevalence of Alzheimer Disease CSF Biomarkers in a Clinical Sample with Subjective Cognitive Impairment.

Background/Aims: Subjective cognitive impairment (SCI) is a trigger for seeking health care in a possible preclinical phase of Alzheimers disease (AD), although the characteristics of SCI need clarification. We investigated the prevalence of psychosocial stress, depressive symptoms and CSF AD biomarkers in SCI and MCI (mild cognitive impairment). Methods: Memory clinic patients (SCI: n = 90; age: 59.8 ± 7.6 years; MCI: n = 160; age: 63.7 ± 7.0 years) included in the Gothenburg MCI study were examined at baseline. Variables were analyzed using logistic regression with SCI as dependent variable. Results: Stress was more prevalent in SCI (51.1%) than MCI (23.1%); p < 0.0005. SCI patients had more previous depressive symptoms (p = 0.006), but showed no difference compared to MCI patients considering current depressive symptoms. A positive CSF AD profile was present in 14.4% of SCI patients and 35.0% of MCI patients (p = 0.001). Stress (p = 0.002), previous stress/depressive symptoms (p = 0.006) and a negative CSF AD profile (p = 0.036) predicted allocation to the SCI group. Conclusion: Psychosocial stress is more prevalent in SCI than previously acknowledged. The high prevalence and long-term occurrence of stress/depressive symptoms in SCI in combination with a low prevalence of altered CSF AD biomarkers strengthens the notion that AD is not the most likely etiology of SCI.