Objective: To determine the influence of type 2 diabetes mellitus on the risk of dementia and AD. Background: Both dementia and diabetes are frequent disorders in elderly people. Methods: Prospective population-based cohort study among 6,370 elderly subjects. At baseline study participants were examined for presence of diabetes mellitus. Nondemented participants were followed up, on average, for 2.1 years. Incident dementia was diagnosed using a three-step screening and comprehensive diagnostic workup. To complete the follow-up, medical files were studied of persons who could not be reexamined. We estimated relative risks with proportional hazard regression, adjusting for age, sex, and possible confounders. Results: During the follow-up, 126 patients became demented, of whom 89 had AD. Diabetes mellitus almost doubled the risk of dementia (relative risk [RR] 1.9 [1.3 to 2.8]) and AD (RR 1.9 [1.2 to 3.1]). Patients treated with insulin were at highest risk of dementia (RR 4.3 [1.7 to 10.5]). Conclusion: The diabetes attributable risk for dementia of 8.8% suggests that diabetes may have contributed to the clinical syndrome in a substantial proportion of all dementia patients.

Diabetes mellitus and the risk of dementia The Rotterdam Study

The relation between diabetes and major types of dementia is controversial. This systematic review examines the incidence of dementia in people with diabetes mellitus. We identified 14 eligible longitudinal population-based studies of variable methodological quality. The incidence of "any dementia" was higher in individuals with diabetes than in those without diabetes in seven of ten studies reporting this aggregate outcome. This high risk included both Alzheimer's disease and vascular dementia (eight of 13 studies and six of nine studies respectively). Detailed data on modulating and mediating effects of glycaemic control, microvascular complications, and comorbidity (eg, hypertension and stroke) were generally absent. The findings of mechanistic studies suggest that vascular disease and alterations in glucose, insulin, and amyloid metabolism underlie the pathophysiology, but which of these mechanisms are clinically relevant is unclear. Further high quality studies need to be initiated, with objective diabetes assessment, together with reliable methods to establish the contribution of vascular disease and other comorbidity to dementia.

Risk of dementia in diabetes mellitus: a systematic review

Aim: To estimate the prevalence of Alzheimer’s disease (AD) and other dementias in the USA using a nationally representative sample. Methods: The Aging, Demographics, and Memory Study sample was composed of 856 individuals aged 71 years and older from the nationally representative Health and Retirement Study (HRS) who were evaluated for dementia using a comprehensive in-home assessment. An expert consensus panel used this information to assign a diagnosis of normal cognition, cognitive impairment but not demented, or dementia (and dementia subtype). Using sampling weights derived from the HRS, we estimated the national prevalence of dementia, AD and vascular dementia by age and gender. Results: The prevalence of dementia among individuals aged 71 and older was 13.9%, comprising about 3.4 million individuals in the USA in 2002. The corresponding values for AD were 9.7% and 2.4 million individuals. Dementia prevalence increased with age, from 5.0% of those aged 71–79 years to 37.4% of those aged 90 and older. Conclusions: Dementia prevalence estimates from this first nation

https://www.medpagetoday.com/upload/2007/11/1/000109998.pdf

Prevalence of dementia in the United States: the aging, demographics, and memory study.

The distribution and density of neurofibrillary tangles and amyloid plaques was studied in a unique series of cases whose premortem cognitive status had been assessed with the Clinical Dementia Rating (CDR), including 39 nondemented cases (CDR 5 0; age, 51‐ 88 years), 15 very mildly demented cases (CDR 5 0.5), and 8 severely demented (CDR 5 3) cases. The initial formation of tangles and plaques in healthy aging appeared to be independent of each other. Tangles were found in all the nondemented cases, especially in hippocampal and parahippocampal areas; the average tangle concentration increased exponentially with age. In contrast, plaques were absent in some brains up to age 88, and the earliest plaque formation in other cases occurred in the neocortex, in patches of diffuse plaques. Widely distributed neuritic as well as diffuse plaques throughout neocortex and limbic structures characterized a further group of nondemented cases. In these cases there was also a substantial increase over other nondemented cases, both in the number of tangles and in the rate of increase in tangles with age, suggesting an interaction between amyloid and neurofibrillary change at this stage. Such cases closely resemble CDR 5 0.5 cases, and it is proposed they represent “preclinical” Alzheimer’s disease. Price JL, Morris JC. Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol 1999;45:358 ‐368 It is generally recognized that the incidence of Alzheimer’s disease (AD) is age related, increasing exponentially after the sixth decade of life. 1 Neurofibrillary tangles and b-amyloid plaques are commonly reported to occur in the brains of aged individuals, even without clinical criteria for AD. 2‐ 4 Despite this, recent studies have suggested that when AD or other disorders are carefully excluded, aging itself may not result in substantial cognitive or neuronal loss. 5‐7 In contrast, even the mildest stage of dementing change may indicate the presence of AD, as supported by sufficient plaques and tangles for pathological diagnosis of the disease, 8,9 and substantial neuronal loss in vulnerable areas such the entorhinal cortex 6 . To define the pattern of tangle and plaque formation during healthy aging, it is necessary to identify and study individuals without even very slight cognitive or memory impairment. We have an opportunity to study these issues, because of availability of a unique series of nondemented and very mildly demented cases who were assessed with the Clinical Dementia Rating (CDR). 10 This instrument is sensitive enough to identify nondemented cases accurately, as well as to recognize the earliest clinically detectable stage of AD (CDR 5

Tangles and plaques in nondemented aging and “preclinical” Alzheimer's disease

http://www.faculty.umb.edu/pjt/epi/jick00.pdf

Statins and the risk of dementia.

Background: Incidence studies have been relatively neglected in psychiatric epidemiology. They are particularly important for dementia, since prevalence rates are affected by length of survial, which itself falls with increasing age and presence of dementia. Methods: Two-wave community study of 1195 elderly subjects aged older than 75 years, restudied 2.4 years after a community prevalence study. A two-stage method was used, comprising the Mini-Mental State Examination followed in a stratified sample by the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) interview. Incidence rates were based on personyears at risk. Results: Annual incidence rates for dementia were 2.3% for subjects initially aged 75 to 79 years, 4.6% for ages 80 to 84 years, and 8.5% for ages 85 to 89 years, approximately doubling every 5 years. Rates did not differ significantly by sex, educational level, or social class. Twice as many additional individuals received a diagnosis of minimal dementia not reaching case threshold. Conclusions: The findings show high rates of new onset dementia, increasing markedly with age, and suggest rapid acceleration of one or more processes that is common in advanced age.

Incidence of dementia in a population older than 75 years in the United Kingdom.

The contribution of vascular pathology to the manifestation of dementia and the importance of vascular risk to measures of cognitive function is being increasingly recognized. In particular, confirmation of this risk points towards approaches for prevention in large sections of the population. Information on determinants of incident dementia is increasing, but still relatively few studies of risk have been based on incident cases of dementia in very elderly populations. In this study based on incident cases of dementia in a population aged 75 and over, vascular risks were obtained from informants of the respondents with incident dementia. When compared with controls the factors associated with incident dementia were history of heart attack (odds ratio 2.9), transient ischaemic attacks (4.8), cerebrovascular accidents (3.4), family history of first-degree relatives with dementia (4.0), and occupational exposure to vibrating instruments (1.4). If only Alzheimer's disease, clinically diagnosed, was included, diabetes (1.4) and a history of dementia in first-degree relatives (6.6) emerged. Thus, vascular risk continues to be of importance in the oldest age groups.

Vascular risks and incident dementia: results from a cohort study of the very old.

BACKGROUND In developed countries, most dementia appears to be due to Alzheimer's disease and vascular dementia. We report rates for incidence of subtypes of dementia based on clinical diagnosis.

METHOD This study was a 2.4-year (s.d. 2.6 months) follow-up of a cohort aged 75 years and over, seen initially in a prevalence study of dementia. A screening interview in 1173 survivors was followed in a subsample of 461 respondents by a diagnostic interview 1.8 months after screening (s.d. 1.5 months). This comprised a standardised interview with respondent and informant, with venepuncture where possible. Clinical diagnoses of subtypes were made by specified criteria.

RESULTS The incidence of Alzheimer's disease of mild and greater severity was 2.7/1000 person-years at risk (1.6-4.4); in men 1.5 (0.8-2.7) and in women 3.3 (1.8-5.9). The incidence of vascular dementia was 1.2/100 person-years at risk (0.7-1.9); in men 1.1 (0.4-2.8) and in women 1.2 (0.7-2.0). Alzheimer's disease, but not vascular dementia, showed a marked increase with age, particularly in women. Rates for minimal dementia of different subtypes showed similar age and sex effects, but were much higher for Alzheimer's disease than vascular dementia.

CONCLUSIONS The striking rise in incidence rates of dementia in the very old appear to be due to Alzheimer's disease, while rates for vascular dementia remain relatively constant. These trends are particularly marked for minimal dementia, but emphasise the importance of Alzheimer's disease in the community as a cause of cognitive decline of all degrees.

Incidence of clinically diagnosed subtypes of dementia in an elderly population. Cambridge Project for Later Life.

The Cambridge Cognitive Examination (CAMCOG) is a concise neuropsychological test for the assessment of cognitive impairment in elderly people. It was designed specifically to assist in the diagnosis of dementia in an early stage. CAMCOG assesses a broad range of cognitive functions, as is required for the diagnosis of dementia, and it minimizes floor and ceiling effects by covering a range of item difficulty. We report here some psychometric properties of the CAMCOG in two stages of a population survey of people over the age of 75 years. Total score on the CAMCOG was found to have excellent internal reliability and test-retest reliability. the reliability of the individual subscales, which corresponded to different cognitive abilities, was also acceptable. Principal components analysis on the individual CAMCOG items revealed two easily interpretable factors, corresponding to general intelligence and memory. CAMCOG scores were very effective in differentiating between demented and nondemented ind...

Claire Barkley

Papers

Incidence of dementia in a population older than 75 years in the United Kingdom.

Vascular risks and incident dementia: results from a cohort study of the very old.

Incidence of clinically diagnosed subtypes of dementia in an elderly population. Cambridge Project for Later Life.

Psychometric properties of the CAMCOG and its efficacy in the diagnosis of dementia

The prevalence of depression in a cohort of the very elderly