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PubMed2003

Testing correlation of cognitive decline at adjacent stages of dementia.

This paper studies the correlation of cognitive progression for subjects whose dementia has made a transition from a milder stage of severity to the next stage of impairment. We model the progression of cognitive decline at adjacent stages of dementia by using a general linear mixed model. We also propose a three-step procedure to detect the best configuration of the covariance matrices for the random components in the model. After the best configuration of covariance matrices for the random components in the model is determined, we then recommend another two-step process to test whether there exists a significant correlation between the rate of cognitive decline before the transition, the cognitive status at the transition time, and the rate of cognitive decline after the transition. In addition, we present asymptotic confidence interval estimates for the correlations associated with a transition. This method is applied to several composite psychometric factor scores in the longitudinal database from the Alzheimer's Disease Research Center (ADRC) at Washington University in St. Louis.

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PubMed1997

Psychometric considerations when measuring cognitive decline in Alzheimer's disease.

Measuring cognitive decline is important for both clinical and basic research purposes, but to do so is a complicated methodologic and statistical exercise. Some promising predictive measures have been identified, such as baseline severity of disease, early language deterioration, other early behavioral disturbance and extrapyramidal signs. Nevertheless, investigations of demographic, cognitive and biologic variables have not consistently identified factors affecting differences in the course or rate of decline. Moreover, contradictory results using similar measures are common. Such contradictory results may be attributed, in part, to differences among samples, cognitive tests selected, research design, and methods of statistical analysis. Large samples of patients with dementia examined repeatedly for long time periods are needed. However, tests developed for initial screening, diagnosing and categorizing Alzheimer's disease are not necessarily the most appropriate for longitudinal studies of disease course. New instruments with a broader range of item difficulty, and less susceptibility to floor and ceiling effects must be developed. Also, standardized ways of defining cognitive decline are needed which are more sophisticated than simple change scores. Standardization will improve the ability to compare investigations and perhaps reconcile apparent differences in results.

Alzheimer Disease↗

PubMedDate not supplied

Is depression a risk factor for dementia or cognitive decline? A review.

BACKGROUND: It is generally accepted that depression can be associated with significant cognitive deficits and that depression can be comorbid with dementia. OBJECTIVE: This review seeks to go further and ask whether depression earlier in life can be a risk factor for subsequent dementia or for cognitive decline. METHODS: A review was made of the epidemiological evidence from case-control and prospective studies that depression is a risk factor. The literature was also reviewed in relation to six hypotheses that might explain an association: (1) depression treatments are a risk factor for dementia, (2) dementia and depression share common risk factors, (3) depression is a prodrome of dementia, (4) depression is an early reaction to cognitive decline, (5) depression affects the threshold for manifesting dementia, and (6) depression is a causal factor in dementia. RESULTS: A meta-analysis found that depression was associated with an increased risk of subsequent dementia in both case-control studies (95% CI for relative risk: 1.16-3.50) and prospective studies (95% CI: 1.08-3.20). There was little support for hypotheses 1 and 2. The other hypotheses have limited support, but warrant further research. CONCLUSION: There is sufficient evidence to take seriously the possibility that depression is a risk factor for dementia and cognitive decline. Further work is needed to examine depression as a prodrome of vascular dementia, depression as an early reaction to perceived cognitive decline, the effects of depression on the threshold for manifesting dementia, and depression as a source of hippocampal damage through a glucocorticoid cascade.

Case-Control Studies↗

PubMed2005

Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons.

BACKGROUND: Deficiencies in folate and vitamin B12 have been associated with neurodegenerative disease. OBJECTIVE: To examine the association between rates of age-related cognitive change and dietary intakes of folate and vitamin B12. DESIGN: Prospective study performed from 1993 to 2002. SETTING: Geographically defined biracial community in Chicago, Ill. PARTICIPANTS: A total of 3718 residents, 65 years and older, who completed 2 to 3 cognitive assessments and a food frequency questionnaire. MAIN OUTCOME MEASURE: Change in cognitive function measured at baseline and 3-year and 6-year follow-ups, using the average z score of 4 tests: the East Boston Tests of immediate and delayed recall, the Mini-Mental State Examination, and the Symbol Digit Modalities Test. RESULTS: High folate intake was associated with a faster rate of cognitive decline in mixed models adjusted for multiple risk factors. The rate of cognitive decline among persons in the top fifth of total folate intake (median, 742 microg/d) was more than twice that of those in the lowest fifth of intake (median, 186 microg/d), a statistically significant difference of 0.02 standardized unit per year (P = .002). A faster rate of cognitive decline was also associated with high folate intake from food (P for trend = .04) and with folate vitamin supplementation of more than 400 microg/d compared with nonusers (beta = -.03, P<.001). High total B12 intake was associated with slower cognitive decline only among the oldest participants. CONCLUSIONS: High intake of folate may be associated with cognitive decline in older persons. These unexpected findings call for further study of the cognitive implications of high levels of dietary folate in older populations.

Age Factors↗

PubMed2000

Cognitive decline is associated with systemic oxidative stress: the EVA study. Etude du Vieillissement Artériel.

OBJECTIVE: To determine whether systemic oxidative stress status is associated with cognitive decline. DESIGN: A longitudinal population-based study. SETTING: A cohort study of older subjects in Nantes, France. PARTICIPANTS: A total of 1166 high cognitive functioning subjects aged 60 to 70 in the Etude du Vieillissement Arteriel (EVA) cohort with a 4 year follow-up. MEASUREMENTS: Subjects completed a baseline interview and a global cognitive test (Mini-Mental Status Examination (MMSE)). Blood samples were obtained at baseline to determine plasma levels of selenium, carotenoids, thiobarbituric acid reactant substances (TBARS), an indicator of lipoperoxidation, and red blood cell vitamin E. Risk of cognitive decline, defined as a loss of 3 points in MMSE score between baseline and the 4 year follow-up, was assessed by oxidative stress level. RESULTS: Subjects with the highest levels of TBARS show an increased risk of cognitive decline (adjusted odds ratio (OR) = 2.25; confidence interval (CI) 95% = 1.26-4.02). This result is reinforced in the lower antioxidant status subgroup. Subjects with low levels of selenium have an increased risk of cognitive decline (OR = 1.58; CI 95% = 1.08-2.31) after adjustment for various confounding factors. CONCLUSIONS: These results suggest that increased levels of oxidative stress and/or antioxidant deficiencies may pose risk factors for cognitive decline. The direct implication of oxidative stress in vascular and neurodegenerative mechanisms that lead to cognitive impairment should be further explored.

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PubMed1998

Occupation type as a predictor of cognitive decline and dementia in old age.

OBJECTIVE: To assess whether an individual's main occupation predicts cognitive decline or dementia. METHODS: The data were taken from a longitudinal study of 518 men aged 70 or over. Main occupation was coded into one of John Holland's six occupational categories. The subjects completed four cognitive tests and were diagnosed for dementia on two occasions three and a half years apart. The cognitive tests were the Mini-Mental State Examination, Episodic Memory Test, Symbol-Letter Modalities Test and National Adult Reading Test. Informants also completed the Informant Questionnaire on Cognitive Decline in the Elderly. Dementia was diagnosed by the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised (DSM-III-R) and ICD-10 criteria using the Canberra Interview for the Elderly. RESULTS: Cross-sectional analysis of the wave 1 data showed that the realistic occupations, which include trade, technical and some service occupations, had poorer cognitive performance and a higher prevalence of DSM-III-R dementia. These differences held even when age, education and native English were statistically controlled. The greatest occupational difference was on the National Adult Reading Test, which estimates pre-morbid ability. By contrast, there were no occupational differences in longitudinal change in cognitive test performance, informant reports of cognitive decline or incident cases of dementia over three and a half years. CONCLUSION: Cross-sectional occupational differences on cognitive tests and in dementia prevalence are due to differences in pre-morbid ability rather than to differences in rate of cognitive decline.

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PubMed2004

Thought disorder, pragmatic language impairment, and generalized cognitive decline in schizophrenia.

BACKGROUND: Schizophrenia is associated with pragmatic language impairment (PLI), a reduced ability to communicate intention in a rule-governed fashion. Two explanations for PLI include that PLI is equivalent to thought disorder and that PLI is secondary to generalized cognitive decline. OBJECTIVES: The aims of this study were to demonstrate PLI in schizophrenia and to test which of these explanations best accounts for the relationships among thought disorder, PLI, and generalized cognitive decline. METHOD: Schizophrenia (n=20) and control (n=26) participants provided speech samples that were scored for thought disorder (type-token ratio and Cloze procedure) and PLI [Profile of Pragmatic Impairment in Communication (PPIC)]. Generalized cognitive decline was determined from discrepancies between current and premorbid verbal IQ. RESULTS: Patients with schizophrenia exhibited significant PLI and generalized cognitive decline. There was no evidence of an association between thought disorder and PLI. Moreover, generalized cognitive decline predicted PLI (r(2)=0.33 to 0.59) but not thought disorder (r(2)=0.02 to 0.06). CONCLUSIONS: The results conformed to a predicted pattern of associations based on the notion that PLI in schizophrenia is secondary to generalized cognitive decline.

Adult↗

PubMedDate not supplied

Postural hypotension and EEG variables predict cognitive decline: results from a 5-year follow-up of healthy elderly women.

Quantified electroencephalographic activity (EEG) has been used to study normal ageing and dementia. Few studies have described longitudinal changes in the very old. A cognitive decline has been described in subjects with white-matter lesions and hypertension but the association with hypotension is unclear. Our aim was to study the predictive value of quantified EEG for the development of cognitive decline and associations with postural hypotension. Participants. Thirty-three healthy women aged 75-95 years, with no signs of cerebrovascular disease, dementia or acute illness at baseline examination took part in a longitudinal 5-year follow-up study. The women were recruited from a random selection using the Municipal Registry. Quantified EEG was assessed twice and recorded on a Siemens-Elema connected to a Biological Banker. The medical and neuropsychological examination was conducted twice. Dementia was classified according to DSM criteria. The assessment included Mini-Mental Scale Examination (MMSE), spatial and vocabulary tests. Blood pressure was measured in supine position and an orthostatic test was performed with continuous ECG recording. Seven women (cases) developed cognitive decline at the 5-year follow-up, defined as newly developed MMSE < 27 and dementia symptoms. Low beta activity at baseline predicted development of cognitive decline. The women who remained healthy at follow-up showed an increase of alpha and theta activity. The cases had a higher orthostatic blood pressure fall during tilting at baseline (16 mm Hg) than the controls (1 mm Hg, p < 0.01). The orthostatic reaction was correlated with increased levels of theta and alpha activity at follow-up (r = -0.47 to -0.52; p < 0.01). Low beta activity predicts for cognitive decline in the elderly and an orthostatic blood pressure reaction is a risk factor for cognitive decline.

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PubMed2005

Is benzodiazepine use a risk factor for cognitive decline and dementia? A literature review of epidemiological studies.

BACKGROUND: A major public health issue is to determine whether long-term benzodiazepine use may induce cognitive deficits persisting after withdrawal. The aim of the present review was to examine findings from prospective studies carried out in general population samples exploring whether exposure to benzodiazepines is associated with an increased risk of incident cognitive decline. METHOD: Using a MEDLINE search and a hand-search of related references in selected papers, we retrieved original studies published in peer-reviewed journals that explored in general population samples the association between benzodiazepine exposure and change in cognitive performance between baseline and follow-up assessment. RESULTS: Six papers met the inclusion criteria. Two studies reported a lower risk of cognitive decline in former or ever users, two found no association whatever the category of user, and three found an increased risk of cognitive decline in benzodiazepine users. CONCLUSIONS: The discrepant findings obtained by studies examining the link between benzodiazepine exposure and risk of cognitive decline may be due to methodological differences, especially regarding the definitions of exposure and cognitive outcome. As a large proportion of subjects are exposed to benzodiazepines, a small increase in the risk of cognitive decline may have marked deleterious consequences for the health of the general population. This issue needs to be explored further by pharmaco-epidemiological studies.

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PubMed1995

Temporal lobe perfusion on single photon emission computed tomography predicts the rate of cognitive decline in Alzheimer's disease.

OBJECTIVE: To examine the ability of relative regional cerebral blood flow as measured by single photon emission computed tomography to predict longitudinal course of cognitive decline in Alzheimer's disease. DESIGN: Single photon emission computed tomography using the blood flow tracer 123I-N-isopropyl-p-iodoamphetamine was performed at initial evaluation and was used to predict the rate of cognitive decline over a follow-up period from 1 to 4 years. SETTING: Outpatient university dementia clinic and center for functional imaging. PARTICIPANTS: Twenty-nine patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probably or possible AD. RESULTS: Temporal lobe regional cerebral blood flow ratio at initial evaluation correlated with rate of decline in Mini-Mental State Examination over the longitudinal follow-up. Temporal regional cerebral blood flow ratio also predicted rate of decline of specific memory measures on the California Verbal Learning Test. Neither parietal nor frontal ratios predicted rate of cognitive decline. Dorsolateral frontal hypoperfusion was associated with the emergence of perseverative behaviors over time. Age, prior dementia duration, estimated prior rate of decline, and initial severity did not predict rate of cognitive decline. CONCLUSION: Results suggest that regional perfusion on single photon emission computed tomography may predict cognitive decline in Alzheimer's disease better than these demographic and course variables.

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PubMed2005

APOE genotype and cognitive decline in a middle-aged cohort.

BACKGROUND: Most longitudinal studies of nondemented persons have reported greater cognitive decline among APOE epsilon4 carriers vs noncarriers. However, most studies involved elderly samples (aged 65+) and were not large enough to examine the three APOE alleles separately. METHODS: Change in cognitive function was examined over a 6-year period using three neuropsychological tests among four APOE genotype groups (epsilon2/2 + epsilon2/3, epsilon3/3 (referent), epsilon4/2 + epsilon4/3, epsilon4/4). The population-based sample included 1,693 African Americans and 6,202 Caucasians initially ages 47 to 68. RESULTS: There was increasingly greater cognitive decline from the epsilon2 group to the epsilon4/4 group in Caucasians for two of the three tests. The combination of APOE epsilon4 with hypercholesterolemia or diabetes showed the greatest cognitive decline. Among African Americans, only the test measuring psychomotor speed showed associations with APOE genotype. CONCLUSIONS: APOE epsilon4 is associated with greater cognitive decline in middle-aged Caucasian individuals, with a reduced decline among epsilon2 carriers. This suggests that the processes by which APOE genotype mediates dementia risk are operative well in advance of overt dementia.

Black or African American↗

PubMed1994

Cognitive declines correlate with decreased cortical volume and perfusion in dementia of Alzheimer type.

Cerebral CT changes are correlated with cognitive declines among 18 patients with probable dementia of Alzheimer type (DAT) (7 men, 11 women, mean age 75.4 years) and are compared for control purposes with similar measures among 18 age-matched normal volunteers (8 men, 10 women, mean age 73.7 years). Mean follow-up intervals are 28.6 months for DAT and 27.0 months for controls. For DAT, annual rates for ventricular volume enlargement are +9.2% and for cortical atrophy are -2.1%. Annual reductions in regional cerebral perfusions per 100 g brain/min, are: total cortex -1.1 ml, frontal -1.2 ml, temporal and parietal -0.9 ml, basal ganglia -1.6 ml, thalamus -2.5 ml, total white matter -0.6 ml, frontal white matter -0.7 ml. At entry evaluation, compared to normals, DAT patients had reduced CT densities in white matter, but not in cortex. Nevertheless, cortical CT densities declined progressively at annual rates of -0.72 Hounsfield units (HU), but remained constant in white matter. Annual point score declines for Cognitive Capacity Screening Examinations were -2.0 and for Mini Mental State: -2.8. Controls showed no cognitive change. Multiple regression analyses correlate cognitive declines with: (1) reductions in perfusion within parietal cortex (p = 0.015), (2) decreases in cortical volume (p = 0.019), and (3) decreases in HU within subcortical gray matter (p = 0.007).

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PubMed2003

[Factors related to discrepancy in evaluation on functional capacity between reports by community-dwelling older people with cognitive decline and their family members].

Overestimation or underestimation of functional capacity in community-dwelling older people with cognitive impairment was evaluated between the responses of subjects and family members (proxies) by cognitive function level. Out of all the residents aged 65 years and over living in Yoita town, Niigata Prefecture in 2000 (n = 1,673), 1,544 voluntarily participated in the interview survey held at community halls or at home (92.3% response). They underwent the Mini-Mental State Examination (MMSE) for assessment of cognitive function and answered questionnaires comprising socio-demographic, psychological, physical and medical, and social activity items (2000/11). According to the age of the subject and MMSE score, we defined cognitive decline (MMSE scores < 1 SD below age-specific means, n = 371). 158 pairs among 371 subjects with cognitive decline and their proxies participated in a follow-up survey (2001/11). The subjects themselves underwent MMSE again. 136 subject-proxy pairs reported any complaints of memory-related problem and evaluated higher-level functional capacity (TMIG-IC, Tokyo Metropolitan Institute of Gerontology Index of Competence). We established criteria at follow-up survey as follows: control (n = 29), MMSE scores > 1 SD below age-specific means and CDR (Clinical Dementia Rating) = 0: mild cognitive decline (MCD) (n = 54), 21 < or = MMSE scores < 1 SD below age-specific means or CDR = 0.5); and severe cognitive decline (SCD) (n = 53), MMSE scores 20 < or = CDR > 0.5. SCD subjects significantly overestimated total and Instrumental Self-Maintenance scores in TMIG-IC more than control or SCD subjects. Multiple logistic regression analyses indicated that complaints of memory by the proxy, response by spouse, and higher levels of education were extracted as significantly independent variables affecting overestimation for functional capacity. On the other hand, aging affected underestimation.

Activities of Daily Living↗

PubMed2003

A systematic review of cognitive decline in the general elderly population.

BACKGROUND: The public health impact of cognitive decline and dementia is increasing as the population ages. Studies exploring therapies or risk factors for cognitive impairment require understanding of expected age-related decline. OBJECTIVE: To establish the rate of age-related cognitive decline in the general elderly population. DESIGN: Systematic review of studies of cognitive decline in the general elderly population. Medline, Embase and PsycINFO databases were searched using an adapted version of McMaster's aetiology, causation and harm strategies and the Cochrane Dementia and Cognitive Impairment Group strategy. Grey literature was explored and experts contacted. A second observer was involved at all stages and quality appraisal of included studies was performed. Included studies were representative, community-based, cohort studies of people aged over 60, incorporating individuals with dementia. RESULTS: Identification of 5990 abstracts and retrieval of 163 full texts led to inclusion of 19 papers. Heterogeneity made narrative review the appropriate method of data synthesis. Some degree of cognitive impairment with increasing age was found in all studies, although the extent varied. The prevalence of cognitive impairment and the rate of decline increased with age. Studies were of variable quality. CONCLUSIONS: Cognitive decline is almost universal in the general elderly population and increases with age. Improved communication between researchers and between clinicians to identify a core minimum data set of neuropsychological tests that could be used in different populations would support consistent study design and meta-analysis, helping to quantify the true rate of cognitive decline in the elderly and assisting diagnosis in clinical practice.

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PubMed2001

Physical activity and cognitive decline, the role of the apolipoprotein e4 allele.

PURPOSE: The purpose of this study was to investigate the association between level of physical activity and risk of cognitive decline at older age and its variation across carriers and noncarriers of the apolipoprotein e4 allele. METHODS: The association was studied in a cohort of 347 elderly Dutch men. Mean age of the study subjects was 74.6 +/- 4.3 yr in 1990. Physical activity was categorized in "maximal 1 h per day" versus "more than 1 h per day." Cognitive decline was defined as a drop MMSE score > 3 points between 1990 and 1993. RESULTS: After adjusting for age, education, alcohol consumption, smoking and cognitive functioning at baseline, subjects with maximal 1 h of physical activity per day had a two-fold increased risk of cognitive decline (OR 2.0, 95% CI: 0.9-4.8) as compared with the rest. Risk of cognitive decline was particularly strong in carriers of the APOE*4 allele (adjusted OR 3.7, 95% CI: 1.1-12.6). CONCLUSION: The authors conclude that promotion of physical activity at older age may reduce the risk of cognitive decline. The existence of subgroups with a particularly high risk may have important implications for prevention strategies.

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PubMed1996

Language functions in incipient cognitive decline in multiple sclerosis.

Although the mechanisms of cognitive impairment in multiple sclerosis (MS) have been extensively studied, evaluation of language functions has been given little attention. In the present study, we evaluated whether impairment of language functions is associated with cognitive decline in MS. We studied naming, reading, and writing performance of two carefully matched patient groups differing only with respect to cognitive status. In language tasks, the patients with incipient cognitive decline not only demonstrated performance slowness but also made more errors than the patients with preserved cognitive capacity and the healthy controls. The comprehensive naming error analysis revealed that the cognitively deteriorated patients produced error types not present in the other two study groups. Contrary to previous suggestions, the present study indicates that impaired language performances in MS are attributable to mild cognitive deterioration rather than to sensory or motor factors. Thus, assessment of language functions should be included in neuropsychological evaluations of MS patients.

Adult↗

PubMed2004

Loss of serotonin 5-HT2A receptors in the postmortem temporal cortex correlates with rate of cognitive decline in Alzheimer's disease.

RATIONALE: Previous studies have demonstrated reductions of serotonin 5-HT 2A receptors in the neocortex of Alzheimer's disease (AD) patients. However, it is unclear whether such losses play a role in the cognitive decline of AD. OBJECTIVES: To correlate neocortical 5-HT 2A receptor alterations with cognitive decline in AD. METHODS: Postmortem frontal and temporal cortical 5-HT 2A receptors were measured by [3H]ketanserin binding in aged controls as well as in a cohort of AD patients who had been longitudinally assessed for cognitive decline and behavioral symptoms. RESULTS: 5-HT 2A receptor densities in both regions were reduced in severely demented AD patients compared to age-matched controls. In the temporal cortex, this reduction also correlated with the rate of decline of Mini-Mental State Examination (MMSE) scores. The association between 5-HT 2A receptor loss and cognitive decline was independent of the effects of choline acetyltransferase (ChAT) activity and presence of behavioral symptoms. CONCLUSIONS: Our data suggest that loss of neocortical 5-HT 2A receptors may predict for faster cognitive decline in AD, and point to serotomimetics as potentially useful adjuvants to cholinergic replacement therapies.

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PubMed2005

Hallucinations, cognitive decline, and death in Alzheimer's disease.

The relation of psychotic symptoms to cognitive decline and mortality in Alzheimer's disease (AD) was examined during a mean of 2.2 years in 478 persons selected from clinical settings. Psychotic symptoms were ascertained at baseline and cognition was assessed semiannually with nine tests from which a global measure was formed. In analyses that controlled for age, sex, race, and education, hallucinations (29.6%), especially visual ones, were associated with more rapid global cognitive decline and increased mortality, even after controlling for baseline level of cognition and use of antipsychotic medication, and the association with mortality increased with higher level of education. Delusions and misperceptions were not strongly related to cognitive decline or mortality. The results suggest that hallucinations in Alzheimer's disease, particularly visual ones, are associated with more rapid progression.

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