Parahippocampal volume deficits in subjects with aging-associated cognitive decline

OBJECTIVE: Neuropathological evidence suggests that the earliest changes in Alzheimer's disease selectively affect the parahippocampal regions of the brain. This study was conducted to determine if otherwise healthy elderly subjects with mild cognitive impairment had structural volume deficits affecting the parahippocampal gyrus. METHOD: Magnetic resonance imaging (MRI) was used to compare global and regional brain volumes in 21 subjects with mild cognitive deficits defined according to the criteria for aging-associated cognitive decline, 22 cognitively intact comparison subjects, and 12 patients with Alzheimer's disease. RESULTS: Compared with the cognitively intact subjects, the subjects with aging-associated cognitive decline had a significantly smaller mean volume of the right parahippocampal gyrus. The subjects with aging-associated cognitive decline had a mean parahippocampal volume that was intermediate between that of the Alzheimer's disease patients and that of the cognitively intact subjects. CONCLUSIONS: Parahippocampal atrophy underlies the observed cognitive deficits in aging-associated cognitive decline. These findings support the hypothesis that aging-associated cognitive decline represents a preclinical stage of Alzheimer's disease.     

Prevalence of mild cognitive impairment: a population-based study in elderly subjects

OBJECTIVES: Mild cognitive impairment (MCI) has been suggested as a term for a boundary area between normal aging and dementia, especially Alzheimer's disease (AD). In follow-up studies, more than 50% of MCI subjects have been converted to dementia in 3-4 years. However, the epidemiology of MCI is not well known. This study was designed to determine the prevalence of MCI in an elderly population. METHODS: A total of 806 subjects (60-76 years of age) from a population-based random sample of 1150 subjects living in the city of Kuopio in eastern Finland were evaluated. Neuropsychological tests and a structured interview including the modified Clinical Dementia Rating (CDR) were used to apply the diagnostic criteria of MCI as proposed by Mayo Clinic Alzheimer's Disease Research Centre. Thus, subjects having a test score more than 1.5 SDs below the age appropriate mean in memory tests and a CDR score of 0.5 but no dementia, were diagnosed as having MCI. RESULTS: A total of 43 subjects, 5.3%, met the MCI criteria. MCI was more prevalent in older and less-educated subjects, but no difference was found between men and women. The CDR appeared to be the most important part of the criteria. The memory tests had less impact on prevalence variables. CONCLUSIONS: The low prevalence of MCI indicate that in a population-based study design its criteria may identify a more homogeneous group of subjects at the lower end of the cognitive continuum as contrasted with various other criteria of cognitive impairment in the elderly population. This is compatible with follow-up studies showing a high probability of dementia in the MCI group. Thus, probable candidates for trials of preventive intervention for dementia can be screened from the elderly population using these diagnostic criteria.     

Risk factors for dementia of Alzheimer type and aging-associated cognitive decline in a Spanish population based sample, and in brains with pathology confirmed Alzheimer's disease

We investigated the environmental and genetic factors for Alzheimer's disease (AD) in Spain and performed a door to door study of a cohort of more than 500 subjects, over 70 years old, from Leganés, a suburban area near Madrid. The cohort was followed for 6 years by neurologists and other health workers and was divided in three groups: normal controls, subjects with aging-associated cognitive decline (AACD) and probable AD or dementia of Alzheimer's type (DAT). Biological variables and polymorphisms of different genes, important in neurodegeneration or reported to be associated with AD, were investigated as putative risk modifiers. These polymorphisms have also been analyzed in 94 brains, 39 from patients with pathologically confirmed AD and 55 controls. The statistical investigation included the evaluation of different individual risks and a multinomial logistic regression analysis to detect predictive factors. The risk of AACD and AD increased with age, feminine gender and history of stroke and decreased with education. The allele ApoE4 increased the risk of AD but not of AACD. When the impact of ApoE4 was added to the model, the effect of education and stroke disappeared as risk modifiers.     

The course of cognitive impairment in preclinical Alzheimer disease: three- and 6-year follow-up of a population-based sample

OBJECTIVES: To examine the ability of the total score and individual items from the Mini-Mental State Examination in predicting the development of Alzheimer disease (AD) across a 3- and 6-year period in a population-based sample, and to describe the longitudinal changes in these measures across the same follow-up periods. DESIGN: Prospective follow-up of a community-based cohort, with 3 times of testing across a 6-year period. At each time of measurement, participants were clinically examined by physicians to identify demented and nondemented participants according to Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, criteria. PARTICIPANTS: The study population consisted of all participants who were nondemented at the first follow-up and participated in the second follow-up examination. Among those, 459 remained nondemented and 73 developed AD during the second follow-up period. RESULTS: Baseline differences in the total Mini-Mental State Examination score and the delayed memory item were seen 6 years before eventual dementia diagnosis (P<.01). Analysis of the longitudinal changes showed no differences in the rate of decline for the incident AD or nondemented group between time 1 and time 2 (P>.10). However, the incident AD group exhibited precipitous declines in 8 of the 10 subscales between time 2 and time 3, the point at which they were clinically diagnosed (P<.01). Logistic regression analyses showed that only the delayed memory item was a significant predictor of who would develop AD, independent of age, sex, and years of education, at both of the first 2 times of measurement (P<.001). CONCLUSIONS: The diagnosis of AD is preceded by a long preclinical phase in which deficits in memory performance are most common. These deficits remain relatively stable up until the time that a dementia diagnosis can be rendered. Arch Neurol. 2000.     

Head injuries and cognitive decline among older adults: a population-based study

OBJECTIVE: To examine the relationship between minor and major head injuries caused by fall accidents and cognitive decline among a cohort of adults age 70 years or older (n = 588). BACKGROUND: Even a mild brain injury may affect cognitive functions. Among older adults, results from case-control studies suggest that the occurrence of head injury is positively associated with the onset of AD. METHODS: The shortened version of the Mini-Mental State Examination (sMMSE) was performed and a set of demographic and clinical variables were collected at the beginning of the study. All falls were recorded during a period of 2.5 years, after which the sMMSE tests were repeated. The risk of falls causing head injury in terms of a defined cognitive decline was examined during another follow-up period of approximately 2.5 years. RESULTS: There was no association between the occurrence of minor head injuries and decline in sMMSE scores. A positive relationship existed between the occurrence of major head injuries and a decline in sMMSE scores. The risk of cognitive decline increased linearly as higher cut-off points were used to define the decline in sMMSE scores-with relative risks (95% CI) of 0.94 (0.47 to 1.90), 1.35 (0.64 to 2.85), 1.75 (0.78 to 3.91), 2.38 (1.02 to 5.52), and 3.72 (1.64 to 8.44)-for a decline of > or =1, > or =2, > or =3, > or =4, and > or =5 points in the sMMSE score. The high risk remained unchanged after adjustment for other potential factors contributing to cognitive decline or dementia. The risk factors associated with falls causing major head injury during the second follow-up period were high age, OR (95% CI) 3.58 (1.87 to 6.85); use of psychotropic medication, 2.04 (1.09 to 3.83); diagnosis of hypertension, 1.80 (0.96 to 3.37); and decline in sMMSE score of >5 points, 2.41 (0.86 to 6.76). CONCLUSIONS: Our results suggest that the occurrence of major head injury increases the risk of cognitive decline. The cause of cognitive decline may be dementia, but this assumption remains to be elucidated in future studies.     

Prevalence of ADHD in a sample of Italian students: A population-based study

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common diagnosis for children and adolescents, although the reported estimates for prevalence are extremely variable worldwide. In the present work we investigate the prevalence of ADHD in a sample of Italian students in a study divided in two phases. In Phase I, a total of 6183 schoolchildren (3178 males and 3005 females, aged range 5–15 years) were screened using the SDAI rating scale for teachers. In Phase II, the parents of children and adolescents who met high screen criteria according to SDAI (cut-off > 14; n = 471, 7.3%) were invited to complete a specific clinical-diagnostic assessment for ADHD with the help of an experienced clinician. Within the entire sample, 107 children dropped out and 12 had mental retardation, whereas 332 subjects (278 males and 54 females, age range 5–14 years) completed the Phase II of the study. One hundred ninety subjects (163 males and 27 females, male: female ratio 6:1, mean age 8 years) were diagnosed with ADHD, indicating a prevalence of 3%. ADHD subtypes included the following: combined (n = 108; 56.8%), inattentive (n = 48; 25.2%) and hyperactive/impulsive (n = 33; 17.3%).Our findings are in line with other reports of ADHD prevalence in the European Countries, and may contribute to underline the impact of this phenomenon in the population, and the need of achieving an improvement in the quality of the public health mental service for the prevention and treatment of ADHD.     

CSF tau protein and FDG PET in patients with aging-associated cognitive decline and Alzheimer’s disease

Introduction

In Alzheimer’s disease (AD), accelerated neurofibrillary tangle formation occurs which is associated with increased tau protein release into the cerebrospinal fluid (CSF). Recent studies found significantly increased CSF tau already in patients at risk of developing AD, indicating its potential as a biochemical marker of AD. Cerebral glucose metabolism is reduced in frontotemporoparietal and cingulate cortices in patients with mild AD. However, few studies have investigated CSF tau protein and cerebral glucose metabolism changes in patients at risk to develop AD.

Methods

48 patients with AD, 88 patients with aging-associated cognitive decline (AACD), and 39 healthy controls were included. In all participants, CSF levels of tau were determined by ELISA at baseline and compared between the diagnostic groups. 14 AACD patients and 14 controls underwent ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET).

Results

AD patients showed the highest CSF tau levels compared with AACD patients and controls. AACD patients had significantly higher tau levels than the controls but lower than the AD patients. AACD patients were characterized by reduced glucose metabolism in bilateral middle temporal cortex, left posterior cingulate cortex, right angular gyrus, and right precuneus compared with controls.

Conclusion

In conclusion, our findings reflect and confirm the clinical judgment of an incipient neurodegenerative disorder in a considerable portion of AACD patients. In patients with AACD, CSF tau levels and cerebral glucose metabolism show an altered pattern comparable with that found in AD and thus may facilitate early diagnosis.     

Symptoms of anxiety and depression in the course of cognitive decline

BACKGROUND/AIMS: Anxiety and depression are common inpatients with cognitive decline and Alzheimer's disease (AD), and recognition and treatment of these symptoms can improve their quality of life. The present study investigates anxiety and depression in different phases of cognitive decline. METHODS: The sample consisted of five groups of elderly people in different phases of cognitive decline; four from a community-based sample (Longitudinal Aging Study Amsterdam), and one group of elderly people diagnosed with AD. ANOVAs were performed to investigate group differences in the severity and prevalence of anxiety and depression, and comorbid anxiety and depressive symptoms. RESULTS: The prevalence rates of anxiety, comorbid anxiety and depressive symptoms and depressive symptoms follow a pattern of an increasing prevalence as cognitive performance declines and a decrease in the prevalence when cognitive functioning is severely impaired. AD patients report fewest anxiety symptoms. CONCLUSION: We found that the prevalence of anxiety symptoms, depressive symptoms and comorbid anxiety and depressive symptoms seems to increase in the early phase of cognitive decline, and decreases as cognitive functioning further declines. Elderly diagnosed with AD report less anxiety as expected, probably due to lack of insight caused by AD.     

Quantitative electroencephalographic correlates of cognitive decline in normal elderly subjects

We obtained a topographic computer analysis of the electroencephalogram in 53 normal elderly subjects. Normal aging was not associated with an increase in slow (delta) activity. However, cognitive performance correlated positively with fast (beta) activity particularly in frontal leads, even after controlling for age, education, occupation, and medication. Five subjects who showed early signs of cognitive decline, had all a marked reduction in beta activity suggesting that this may be an early indication of intellectual loss.     

Severe and persistent regressive behaviour in three elderly subjects without cognitive decline

The appearance of regressive behaviours in the elderly is relatively common. Among these regressive attitudes, there is a relatively high frequency of situations which mimic dementia in the absence of demonstrable organic alterations that justify the presence of a neurodegenerative profile. These generally stem from a primary psychiatric disorder and are referred to as 'pseudodementia'. All these conditions, which are generally accompanied by a marked increase in dependency on the environment, are distinguished by the presence of cognitive impairment and behavioural traits typical of dementia but which are fully reversible on treatment of the primary psychiatric disorder. Here we describe three cases, characterized by their striking discrepancy between clinical profile, with pronounced behavioural alterations similar to dementia-related conduct disorders, culminating in almost complete dependency on the environment, and almost stably intact cognitive performance (assessed through the MMSE), over a mean observation period of approximately five years.     

Diminution of context association memory structure in subjects with subjective cognitive decline

Alzheimer's disease (AD) progresses insidiously from the preclinical stage to dementia. While people with subjective cognitive decline (SCD) have normal cognitive performance, some may be in the preclinical stage of AD. Neurofibrillary tangles appear first in the transentorhinal cortex, followed by the entorhinal cortex in the clinically silent stage of AD. We expected the earliest changes in subjects with SCD to occur in medial temporal subfields other than the hippocampal proper. These selective structural changes would affect specific memory subcomponents. We used the Family Picture subtest of the Wechsler Memory Scale‐III, which was modified to separately compute character, activity, and location subscores for episodic memory subcomponents. We recruited 43 subjects with SCD, 44 subjects with amnesic mild cognitive impairment, and 34 normal controls. MRI was used to assess cortical thickness, subcortical gray matter volume, and fractional anisotropy. The results demonstrated that SCD subjects showed significant cortical atrophy in their bilateral parahippocampus and perirhinal and the left entorhinal cortices but not in their hippocampal regions. SCD subjects also exhibited significantly decreased mean fractional anisotropy in their bilateral uncinate fasciculi. The diminution of cortical thickness over the mesial temporal subfields corresponded to brain areas with early tangle deposition, and early degradation of the uncinate fasciculus was in accordance with the retrogenesis hypothesis. The parahippocampus and perirhinal cortex contribute mainly to context association memory while the entorhinal cortex, along with the uncinate fasciculus, contributes to content‐related contextual memory. We proposed that context association and related memory structures are vulnerable in the SCD stage.     

Prevalence of psychiatric disorders among subjects exposed to a natural disaster

A general practice study was carried out in 3 areas of the province of Naples, in southern Italy: Pozzuoli (PZ), a town exposed to significant seismic events in 1983, Monte Ruscello (MR), a village built to accommodate the victims of the earthquake, and Monte di Procida (MP), a town selected as a control since it is situated near PZ and was not significantly affected by the earthquake. The sociodemographic characteristics of the subjects examined were comparable in the 3 areas. The estimate of the real prevalence of psychiatric disorders according to Diamond & Lilienfeld was found to be higher in PZ and MR than in MP. Neurotic depression was the most frequent psychiatric diagnosis. The relative risk of mental disorders in subjects who reported none one or more social problems compared with those who reported none was more than 4 times greater in PZ and MR than in MP. Social problems also differed qualitatively, being more frequently related to living conditions in PZ and MR and to the primary social network in MP.     

Prevalence and associations of co-morbid insomnia and sleep apnoea in an Australian population-based sample

IntroductionInsomnia and obstructive sleep apnoea (OSA) are the two most prevalent sleep disorders, and frequently co-occur (COMISA) in sleep clinic samples. However, few studies have investigated the prevalence or associations of COMISA in the general population.MethodsWe used population-based online survey data from 2044 Australian adults. The prevalence and associations of insomnia, OSA and COMISA were investigated according to symptom-level, and disorder-level definitions. Insomnia was defined according to chronic difficulties initiating and/or maintaining sleep (DIMS; symptom-level), and ICSD-3 chronic insomnia disorder (disorder-level). OSA was defined according to self-reported frequent obstructive events, snoring or doctor-diagnosed OSA (symptom-level), and doctor-diagnosed OSA (disorder-level). COMISA was defined if both conditions were met (for symptom-level, and disorder-level threshold). Associations with other conditions, and general health were investigated with Poisson regression analyses.ResultsChronic insomnia occurred more frequently among participants with doctor-diagnosed OSA (22.3%), compared to those without (14.3%, p = 0.010). Doctor-diagnosed OSA was more common among participants with chronic insomnia (10.2%) compared to those without (6.2%; p = 0.010). DIMS also occurred more frequently among participants with OSA symptoms (66.6%), compared to those without (47.2%; p < 0.001). Participants with symptom-level COMISA reported increased co-morbid conditions, and worse general health compared to participants with symptoms of insomnia-alone, OSA-alone, or neither insomnia/OSA.ConclusionsCOMISA at symptom and disorder level were common and associated with increased medical and psychiatric co-morbidity, as well as poor general health. More investigation is required to understand bi-directional associations underpinning the high co-morbidity, and improve diagnostic and treatment approaches for COMISA to reduce associated morbidity.     

Longitudinal course of insomnia: Age-related differences in subjective sleepiness and vigilance performance in a population-based sample

Objective

The present study utilized a population-based sample investigating the following aims: (1) compare the longitudinal course of insomnia in middle-aged and older adults and (2) examine age-related differences on subjective complaint and objective performance in middle-aged and older adults based on the course of insomnia.

Methods

1657 middle-aged adults (48.16% male, mean age = 55.35 ± 4.03 years) and 405 older adults (48.40% male, mean age = 70.13 ± 3.88 years) from the Korean Genome and Epidemiology Study (KoGES) were classified into 4 groups — no insomnia (NI), single episode insomnia (SEI), remitted persistent insomnia (PI-R), and ongoing persistent insomnia (PI-O) based on their course of insomnia over 5 time points spaced two years apart. Their performance on the psychomotor vigilance task (PVT) and subjective daytime sleepiness were compared across different insomnia groups, and the results were compared between middle-aged adults and older adults.

Results

Analysis of covariance indicated that subjective daytime sleepiness was significantly different across the insomnia groups in middle-aged adults based on insomnia group (P = < .0001), but, did not affect objective vigilance performance. In contrast, older adults displayed significantly different PVT response time, but not daytime sleepiness, based on insomnia group (P = 0.03).

Conclusion

Insomnia impacts psychomotor performance and subjective sleepiness differently, based on age group. There may be underlying processes associated with the aging that amplifies the impact of insomnia on vigilance performance, yet lessens perceived sleepiness in older adults.