Dementia and depression in elders with mental retardation: a pilot study

A preliminary investigation of cognitive decline and depressive symptomatology is presented with older adults who have mental retardation. A series of different assessment instruments are reviewed and tested in a pilot study. A review of dementia and depression with respect to elders with mental retardation is presented to place the study in perspective. Findings reveal decreasing cognitive ability is associated with higher rates of observed depression and reported behavioral problems. Trends suggested those more elderly displayed more depressive behaviors, psychotropic medication was a common treatment, and cognitive decline was associated with lower initial intellectual levels. Dementia and depression is a complicated symptom complex to identify in aging adults with mental retardation.     

Normal ageing in adults with Down's syndrome: a longitudinal study

The ubiquitous presence of the neuropathoiogy of Alzheimer disease (AD) in individuals with Down's syndrome (DS) over 40 years of age suggests that this group of people will exhibit a high prevalence of dementia of the Alzheimer type (DAT) as they age. The present study indicates that there is a clear discrepancy between the presumed presence of AD neuropathoiogy and the clinical expression of DAT among older people with DS. In the first 6 years of a longitudinal study, the present authors compared 91 adults (31–63 years of age) with DS and mild or moderate mental retardation to 64 adults (3 l –76 years of age) with other forms of mental retardation (MR) on yearly measures of mental status, short-and long-term memory, speeded psychomotor function, and visuospatial organization. The results indicated that, over repeated testing on the verbal long–term memory test, younger participants with DS showed small increases in their scores, while older participants with DS showed very slight decreases. Overall performance scores on this test and a speeded psychomotor task were poorer for both diagnostic groups in individuals aged SO years and older. The magnitude and type of these selective changes in performance were consistent with performance profiles observed in older healthy adults without mental retardation on tests measuring similar cognitive functions. Only four out of the 91 people with DS in the present sample showed changes in funaioning that have led to a diagnosis of possible DAT. and in these individuals, alternative causes of performance declines were concurrently present (e.g, thyroid dysfunction). These findings indicate that some age–associated changes in funaioning are related to ‘normal’ but probably precocious ageing among adults with DS. Furthermore, these findings suggest that adults with DS and mild or moderate mental retardation may be at lower risk for dementia during their fourth and fifth decades of life than previous studies have suggested.     

Incidence of dementia in older adults with intellectual disabilities

Dementia may be more common in older adults with intellectual disability (ID) than in the general population. The increased risk for Alzheimer's disease in people with Down syndrome (DS) is well established, but much less is known about dementia in adults with ID who do not have DS. We estimated incidence rates from a longitudinal study of dementia in older adults with ID without DS and compared them to general population rates. 222 participants with ID without DS aged 60 years and older were followed up an average of 2.9 years later to identify those who had declined in functional or cognitive abilities. Those who screened positive had a comprehensive assessment for dementia, diagnosed using ICD 10 and DSM IV criteria. 134 participants who did not have dementia at initial assessment were alive and interviewed at follow up; 21 (15.7%) were diagnosed with dementia. Overall incidence rate for those aged ≥60 was 54.6/1000 person years (95% CI 34.1–82.3). The highest incidence rate (97.8/1000 person years) was in the age group 70–74. Standardised incidence ratio for those aged ≥65 was 4.98 (95% CI 1.62–11.67). Incidence of dementia in older people with intellectual disabilities are up to five times higher than older adults in the general population. Screening may be useful in this population given the high incident rates, particularly as more effective treatments become available. Studies to explore the underlying aetiological factors for dementia associated with intellectual disability could help to identify novel protective and risk factors.     

Incidence and temporal patterns of adaptive behavior change in adults with mental retardation

The age-associated incidence of significant decline in adaptive behavior and the temporal pattern of decline in specific functional skill domains were examined in 646 adults with mental retardation through 88 years of age. Cumulative incidence of significant decline for adults with Down syndrome increased from less than.04 at age 50 to.67 by age 72, whereas cumulative incidence of significant decline for adults with mental retardation without Down syndrome increased from less than.02 at age 50 to.52 at age 88. Among adults experiencing overall decline, four clusters of behaviors were identified based upon the sequence and magnitude of changes, suggesting a pattern of loss not unlike that noted in the population without mental retardation with dementia.     

Maladaptive behaviors related to adaptive decline in aging adults with mental retardation

Changes in patterns of maladaptive behavior related to age-associated adaptive declines were investigated in 529 adults with mental retardation. Although individuals with no significant adaptive decline displayed stable patterns of maladaptive behavior over a 3-year period, those with declines in function showed more variable patterns. Certain maladaptive behaviors were related to the onset of adaptive declines, with some becoming of increasing concern even before adaptive declines were noted (e.g., lack of boundaries). Other behaviors increased as adaptive declines developed (e.g., withdrawal). In general, findings suggest similarities in the course of age-associated dementia of adults with and without mental retardation and indicate that increases in selected areas of maladaptive behavior may be early indicators of concern for individuals at risk.     

Anticholinergic drugs in late life: adverse effects on cognition but not on progress to dementia

Impaired cognitive function associated with use of anticholinergic drugs may be partly attributed to underlying physical illness and exposure to factors that increase the risk of some physical disorders such as low socioeconomic status (SES) and less education. To estimate the extent of cognitive impairment and risk of progress to dementia associated with anticholinergic drug use and to estimate confounding by gender, APOE, family history of dementia, lower SES, less education, and lower childhood mental ability, we recruited 281 volunteers at age 77-78 without overt dementia who had taken part in the Scottish Mental Survey of 1932. Clinical histories, use of medications, self reported frequency of emotional symptoms and standardized tests of cognitive function were obtained. With and without adjustment for age and childhood IQ, there were significant between-group differences in tests of non-verbal reasoning and spatial ability. During 10 year follow-up, progress to overt dementia was not associated with anticholinergic drugs use on recruitment but female gender and a history of dementia in parent or sibling were associated with dementia. We concluded that anticholinergic drug use in this narrow age range sample was linked to cognitive impairment but not to subsequent dementia.     

Costs and benefits of alternative rehabilitation models

Adaptive behavior skills of 2,144 adults with Down syndrome aged 20–69 years were compared to those of a matched group of 4,172 developmentally disabled people without Down syndrome. Adaptive competence in eight skill domains was examined as a function of etiology, age-group and level of mental retardation. In all behavioural domains, and at all levels of mental retardation, individuals with Down syndrome displayed significantly more age-related deficits than did age-matched controls. In individuals with Down syndrome, substantial age-related deficits in adaptive competence were observed after 49 years of age and were most pronounced after 59 years of age. Our findings support previous suggestions of increased risk for Alzheimer disease among adults with Down syndrome. However, Alzheimer neuropathology is found in people with Down syndrome by 40 years of age; signs of regression in adaptive behavior occur 10–15 years after the presumed onset of pathological processes. These results may suggest that the processes underlying dementia in individuals with Down syndrome can have an extremely prolonged course.     

Dementia in adults with mental retardation: assessment at a single point in time

Dementia status of 273 adults with mental retardation was rated based upon two extensive evaluations conducted 18 months apart. Overall, 184 individuals did not have dementia, 33 had possible or definite dementia, and 66 had findings suggesting uncertain or questionable status. These ratings were compared to binary classifications (dementia vs. no dementia) generated from the Dementia Questionnaire for Persons With Mental Retardation (Evenhuis, 1995) and the IBR Mental Status Examination (Wisniewski & Hill, 1985). When performance was referenced to IQs (established earlier in adulthood), quantitative criteria effectively distinguished between individuals with and without dementia based upon assessment at a single point in time. Findings suggest that procedures of this type could soon contribute to more accurate and rapid diagnoses of dementia.     

Capacity of persons with mental retardation to consent to participate in randomized clinical trials

OBJECTIVE: Adults with mental retardation have histories of cognitive and adaptive deficits posing unique ethical challenges for research consent assessment. This study examined the capacity of persons with mental retardation to consent to participate in randomized clinical trials. METHOD: A total of 150 adults (50 each with mild and moderate mental retardation and 50 comparison subjects without mental retardation) responded to a set of consent questions for a hypothetical randomized clinical trial testing a medication for aggressive disorders. Intelligence, adaptive behavior, medical treatment history, and consent history were evaluated. Univariate and multivariate methods were used to compare performance across and within groups. RESULTS: Comparison subjects scored significantly higher on measures of consent capacity than participants with mild mental retardation, who scored higher than those with moderate mental retardation. Most subjects with mental retardation were able to make a participation choice, and many understood research methods and appreciated the protagonist's disorder and the consequences of participation. Almost half of those with mild mental retardation understood human subject protections. Performance was weakest on understanding the purpose of research and reasoning about whether to participate, suggesting vulnerability to the therapeutic misconception. Psychiatric and experiential factors did not predict consent capacity. CONCLUSIONS: While adults with mental retardation as a group showed consent deficits, many attained consent capacity scores comparable to those of comparison subjects. Investigators should consider individual differences and a consent format suited to deficits in language, memory, and attention before restricting consent opportunities for persons with mental retardation.     

Neuropsychological profiles of persons with mental retardation and dementia

This study examined the use of neuropsychological tests to assist in the differential diagnosis of dementia among persons with mental retardation. The author compared performances of persons with mental retardation and dementia (n = 10) to persons with mental retardation without dementia (n = 12). Participants were matched by IQ (mild or moderate mental retardation), age, presence of Down syndrome, and gender. In addition, all participants in the dementia group had corroborative medical tests (i.e., imaging, EEG, or high tau low AB42 protein testing) consistent with diagnosis of dementia. Test performance was compared on measures of attention and executive functions, language, memory and learning, and a dementia screening. Results from MANOVAs and nonparametric tests revealed significantly lower performance for persons with mental retardation and dementia in all areas assessed. Cut-off scores were also developed for the sample in order to maximize sensitivity and specificity for the test battery. Despite the small sample size, these findings suggest that there are significant measurable differences in several neurocognitive domains between the two groups.     

Atypical epilepsy symptomatology as cause of a dementia like state in a mentally and physically retarded patient

We report on a 50-year-old man with mental retardation and right-sided hemi-paresis. He seemed to be cured from epilepsy. In a short time a mental and physical deterioration developed which looked like a dementia, which was suggested by vascular risk factors. The EEG showed marked epileptic activity characterized by spikes appearing every 10 seconds over the left temporal lobe. After introduction of carbamazepine, a fast and long-term improvement of symptoms was noticed resulting in self sufficiency. The fast and marked effect of an antiepileptic drug being given to the patient with an non-typical reactivation of epilepsy in which the dementia-syndrome was caused by a transitory cognitive impairment due to sub-clinic electric seizures or non-convulsive status epilepticus.     

Prevention and early intervention for vascular dementia in community dwelling elderly: Findings from the Nakayama study

Cerebrovascular disease (CVD) may be the single most common risk factor for age‐associated dementia (in particular for vascular dementia (VaD)), and there is definite potential for prevention and treatment of CVD. After one of the most comprehensive and precise type‐specific prevalence surveys of dementia (first Nakayama study), we have continued the preventive and early interventional approaches to CVD and VaD, including treatment of cardiovascular risk factors. In this cohort study, 88% of patients with ‘vascular cognitive impairment without dementia’, who were alive at 3‐years follow up, were still diagnosed with ‘vascular cognitive impairment without dementia’ and only 12% progressed to dementia. Compared with the results of previous studies, active control of risk factors and prevention of recurrent stroke may reduce the incidence of dementia and slow the progression of cognitive impairment in patients with ‘vascular cognitive impairment without dementia’.     

Premature regression of adults with Down syndrome

Adaptive skills of 2,144 individuals with Down syndrome were compared to a similar group of 4,172 developmentally disabled people without Down syndrome. Activities of daily living and cognitive skills were examined across etiology, age group, and level of mental retardation. For individuals with Down syndrome at all levels of retardation, adaptive competence declined with increasing age to a greater extent than for retarded control subjects. Clear age-related deficits associated with Down syndrome were observed only in people older than 50 years of age. Findings support previous evidence of an increased risk for the clinical signs of Alzheimer's disease among people with Down syndrome; however, signs of dementia appeared later in life than would be predicted from available neuropathological data.     

Sydney Memory and Ageing Study: An epidemiological cohort study of brain ageing and dementia

Abstract

Non-demented community-dwelling older adults aged 70–90 years (n = 1,037) randomly recruited from the electoral roll completed neuropsychological and medical assessments over six years. The overall prevalence of mild cognitive impairment (MCI) at baseline was 36.7%. Risk factors for MCI include APOE ?4 allele carrier status, high homocysteine, heart disease, poor odour identification, low visual acuity and low mental activity, but notable age and sex differences were observed. Neuropsychiatric symptoms were rare; depression was the most common and was associated with cognitive impairment in at least one domain as well as subsequent dementia 2 years later. Poorer cognitively demanding functional abilities were associated with cognitive impairment.

Biomarkers for cognitive impairment and decline were identified. Inflammatory markers and plasma apolipoprotein levels were associated with poorer performance in the attention/processing speed domain. Measures of white matter lesions, white matter integrity, sulcal morphology and tractography were identified as novel biomarkers of early cognitive decline. Stronger deactivation in the posteromedial cortex with increasing memory load on functional MRI predicted future decline.

Compared to previous reports, our prevalence rates of MCI were higher but rates of progression to dementia and reversion to normal were similar, as were risk factors for progression to dementia.     

Connections Between Insomnia and Cognitive Aging

Insomnia is a common sleep disorder among older adults,and a risk factor for poor physical and mental health.However,the relationship between insomnia and cognitive health is not well understood.Here,we review observational studies that have investigated whether insomnia is associated with deficits in objective cognitive performance and an increased risk of dementia,magnetic resonance imaging studies that have assessed grey matter volumes and white matter micro structure,and interventional studies that have explored whether the treatment of insomnia can improve cognitive outcomes.There are inconsistent findings regarding impaired performance in objective cognitive tests and reduced grey matter volumes,and limited,emerging,evidence that suggests that insomnia is associated with an increased risk of dementia and reduced white matter integrity.Although the interventional literature is still in its infancy,there is some indication that treatment may have an impact on vigilance.Well-powered studies examining sources of heterogeneity are warranted.     

Vascular risk factors and cognitive disorders

Delaying the onset of dementia by just a few years could have a major impact on the prevalence of the disease at the population level. Vascular risk factors are modifiable and may offer an important opportunity for preventive approaches. Several studies have shown that diabetes, hypertension, obesity, and smoking are associated with an increased risk of cognitive decline and dementia, but other groups have not observed such a relation. Positive associations were observed mainly in studies where risk factors were assessed in midlife, suggesting that age is an important modulator in the relation between vascular risk factors and cognition. The population attributable risk of dementia is particularly high for hypertension. Associations of vascular risk factors with cognitive decline and dementia are probably mediated largely by cerebrovascular disease, including both stroke and covert vascular brain injury, which can have additive or synergistic effects with coexisting neurodegenerative lesions. To date, randomized trials have not convincingly demonstrated that treating vascular risk factors is associated with a reduction in cognitive decline or dementia risk. Of eight randomized trials testing the effect of antihypertensive agents on dementia risk, only one was positive, and another in a subgroup of individuals with recurrent stroke. In most trials, cognition and dementia were secondary outcomes, follow-up was short and treatment was initiated at an older age. No effect on cognitive decline or dementia could be demonstrated for statins and intensive glycemic control. Future areas of investigation could include differential class effects of antihypertensive drugs on cognitive outcomes and identification of high risk individuals as target population for clinical trials initiated in midlife.     

Hippocampal myo-inositol and cognitive ability in adults with Down syndrome: an in vivo proton magnetic resonance spectroscopy study

CONTEXT: Down syndrome (DS) is the most common genetic cause of mental retardation. However, the biological determinants of this are poorly understood. The serum sodium/myo-inositol cotransporter gene is located on chromosome 21, and myo-inositol affects neuronal survival and function. Nevertheless, few in vivo studies have examined the role of myo-inositol in DS. OBJECTIVE: To determine if people with DS have significant differences in brain myo-inositol concentration from controls and if, within people with DS, this is related to cognitive ability. DESIGN: A case-control study. SETTING: Outpatient. PARTICIPANTS: The sample was composed of 38 adults with DS without dementia (age range, 18-66 years) and 42 healthy controls (age range, 19-66 years). The DS and control groups did not differ significantly in age, sex, ethnic origin, apolipoprotein E status, or handedness. MAIN OUTCOME MEASURES: Hippocampal myo-inositol concentration and cognitive performance, as measured by the Cambridge Cognitive Examination. RESULTS: Hippocampal myo-inositol concentration was significantly higher in people with DS than in controls (P = .006), and within people with DS, increased myo-inositol concentration was significantly negatively correlated with overall cognitive ability (P = .04). CONCLUSIONS: Adults with DS have a significantly increased brain concentration of myo-inositol, and this is associated with reduced cognitive ability. Future studies are required to relate myo-inositol concentration in people with DS to brain development and increased risk for developing Alzheimer disease.     

Cognitive Trajectories in Comorbid Dementia With Schizophrenia or Bipolar Disorder: The South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Case Register

ObjectivesWe aimed to compare trajectories of cognitive performance in individuals diagnosed with dementia with and without severe mental illness (SMI).DesignRetrospective cohort study.SettingWe used data from a large longitudinal mental healthcare case register, the Clinical Record Interactive Search (CRIS), at the South London and Maudsley NHS Foundation Trust (SLaM) which provides mental health services to four south London boroughs.ParticipantsOur sample (N = 4718) consisted of any individual who had a primary or secondary diagnosis of dementia from 2007 to 2018, was 50 years old or over at first diagnosis of dementia and had at least 3 recorded Mini-Mental State Examination (MMSE) scores.MeasurementsCognitive performance was measured using MMSE. Linear mixed models were fitted to explore whether MMSE trajectories differed between individuals with or without prior/current SMI diagnoses. Models were adjusted by socio-demographics, cardiovascular risk, smoking, and medication.Results and conclusionsOur results showed differences in the rate of change, where individuals with comorbid SMI had a faster decline when compared with those that have dementia without comorbid SMI. However, this association was partially attenuated when adjusted by socio-demographics, smoking and cardiovascular risk factors; and more substantially attenuated when medication was included in models. Additional analyses showed that this accelerated decline might be more evident in individuals with bipolar disorders. Future research to detangle the potential biological underlying mechanisms of these associations is needed.     

A cross-sectional test of the similar-trajectory hypothesis among adults with mental retardation

The similar-sequence and the similar-structure hypotheses are the two mainstays of the developmental approach to mental retardation. In the present study, a third way, the similar-trajectory hypothesis, is described and illustrated using the WAIS-R results of adults with and without mental retardation aged from 20 to 54 years. The whole sample (N=633) comprised 306 participants with mental retardation and 327 without mental retardation. Hierarchical regression analyses comparing the two groups showed similar evolutions of scores with increasing age for verbal and performance scales. These results seem to validate the similar-trajectory hypothesis, at least for the present samples and for the aspects of cognitive development considered here. Some weaknesses and implications of the study are considered in the discussion.