Prevalence of Alzheimer’s disease in very elderly people

Polvikoski, Tuomo; Sulkava, Raimo; Myllykangas, Liisa; Notkola, I.-L.; Niinistö, Leena; Verkkoniemi, Auli; Kainulainen, Katariina; Kontula, Kimmo; Pérez‐Tur, Jordi; Hardy, John; Haltia, Matti

doi:10.1212/wnl.56.12.1690

Cited by 172 publications

(110 citation statements)

References 39 publications

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“…[5][6][7][8][9][10][11][12][13][14][15] Preliminary studies that compared the strength of association between dementia diagnosis or cognitive performance and AD neuropathology (neuritic plaques and neurofibrillary tangles) between the young old and the oldest old suggest that the association is weaker among the oldest old 6,13 ; however, these studies were limited by small to moderate size and considered…”

Section: Discussionmentioning

confidence: 99%

Neuropathologic features associated with Alzheimer disease diagnosis

Middleton¹,

Grinberg²,

Miller³

et al. 2011

Neurology

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Objective: To examine whether the association between clinical Alzheimer disease (AD) diagnosis and neuropathology and the precision by which neuropathology differentiates people with clinical AD from those with normal cognition varies by age. Methods:We conducted a cross-sectional analysis of 2,014 older adults (Ն70 years at death) from the National Alzheimer's Coordinating Center database with clinical diagnosis of normal cognition (made Յ1 year before death, n ϭ 419) or AD (at Ն65 years, n ϭ 1,595) and a postmortem neuropathologic examination evaluating AD pathology (neurofibrillary tangles, neuritic plaques) and non-AD pathology (diffuse plaques, amyloid angiopathy, Lewy bodies, macrovascular disease, microvascular disease). We used adjusted logistic regression to analyze the relationship between clinical AD diagnosis and neuropathologic features, area under the receiver operating characteristic curve (c statistic) to evaluate how precisely neuropathology differentiates between cognitive diagnoses, and an interaction to identify effect modification by age group. Results: Conclusion:Clinical AD diagnosis was more weakly associated with neurofibrillary tangles among the oldest old compared to younger age groups, possibly due to less accurate clinical diagnosis, better neurocompensation, or unaccounted pathology among the oldest old. Neurology Age is arguably the strongest risk factor for dementia.1 Those 85 years or older, referred to as the oldest old, accounted for less than 1% of the population in 1996 but comprised approximately 40% of dementia cases.2,3 Despite high prevalence of dementia among the oldest old, cognitive impairment in this age group is not well characterized by symptoms or neuropathology, 4 with relatively few neuropathologic studies of Alzheimer disease (AD) in the oldest old. [5][6][7][8][9][10][11][12][13][14][15] Preliminary studies that compared the strength of association between dementia diagnosis or cognitive performance and AD neuropathology (neuritic plaques and neurofibrillary tangles) between the young old and the oldest old suggest that the association is weaker among the oldest old 6,13 ; however, these studies were limited by small to moderate size and considered

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Section: Discussionmentioning

confidence: 99%

Neuropathologic features associated with Alzheimer disease diagnosis

Middleton¹,

Grinberg²,

Miller³

et al. 2011

Neurology

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“…Several investigators have noted that close to half of demented individuals in the tenth decade are likely to have no obvious pathology to explain their cognitive and functional loss [30,31]. Conversely, approximately one of every three non-demented individuals at age 85 have been reported to have senile plaques and neurofibrillary tangles at autopsy, suggesting a pathological diagnosis of AD despite the lack of clear clinical dementia syndrome [31][32][33]. Initial results in a small group of centenarians also showed that about one third of non-demented participants meet pathological criteria for AD [34].…”

Section: Clinical-pathological Correleations In the Oldest-oldmentioning

confidence: 99%

“…In the Oregon Brain Aging Study [35], participants are aged 85 and over, live in the community, function independently, and have no chronic medical conditions. The Vantaa 85+ Study [31] recruited all people at least 85 years of age living in the city of Vantaa, Finland. Two Swedish studies have used a similar approach to recruiting: one recruited all 95+ year olds registered in the city of Göteborg [48], the other recruited all 90+ year old inhabitants of the Kungsholmen district [49].…”

Section: Investigations In the Oldest-oldmentioning

confidence: 99%

Alzheimers and Dementia in the Oldest-Old: A Century of Challenges

Kawas

Corrada²

2006

CAR

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Alzheimer's disease (AD) is the most common type of dementia in the US and much of the world with rates increasing exponentially from age 65. Increases in life expectancy in the last century have resulted in a large number of people living to old ages and will result in a quadrupling of AD cases by the middle of the century. Preventing or delaying the onset of AD could have a huge impact in the number of cases expected to develop. The oldest-old are the fastest growing segment of the population and are estimated to account for 12% of the population over 65. Establishing accurate estimates of dementia and AD rates in this group is crucial for public health planning. Prevalence and incidence estimates above age 85 are imprecise and inconsistent because of the lack of very old individuals in most studies. Moreover, risk and protective factors in our oldest citizens have been studied little, and clinical-pathological correlations appear to be poor. We introduce The 90+ Study, established to address some of the unanswered questions about AD and dementia in the oldest-old. Our preliminary results show that close to half of demented oldest-old do not have known cerebral pathology to account for their cognitive deficits. Furthermore, the APOE-e4 allele appears to be a risk factor for AD only in the women in our study. In addition to the challenge of preventing and treating AD, the oldest-old will require major investigative energy to better understand the concomitants of longevity, the causes of dementia, and the factors that promote successful aging in oldest citizens.

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“…To elucidate the etiology of AD dementia, attempts have been made to correlate cognitive dysfunction with the classical neuropathological changes in AD, extracellular β-amyloid (Aβ) plaques, intraneuronal neurofibrillary tangles (NFTs), and synaptic/neuronal loss. However, some studies suggest that plaques and NFTs may not directly cause AD dementia since both pathologies can manifest in brains of patients that are not cognitively impaired [10,14,49,56]. Another potential mechanism underlying dementia is synaptic loss, since synaptic markers are decreased in AD brains [16,54,59,62].…”

Section: Introductionmentioning

confidence: 99%

Inflammatory changes parallel the early stages of Alzheimer disease

Parachikova

Agadjanyan

Cribbs

et al. 2007

Neurobiology of Aging

182

118

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Alzheimer disease (AD) is the most prominent cause of dementia in the elderly. To determine changes in the AD brain that may mediate the transition into dementia, the gene expression of approximately 10,000 full-length genes was compared in mild/moderate dementia cases to non-demented controls that exhibited high AD pathology. Including this latter group distinguishes this work from previous studies in that it allows analysis of early cognitive loss. Compared to non-demented high-pathology controls, the hippocampus of AD cases with mild/moderate dementia had increased gene expression of the inflammatory molecule major histocompatibility complex (MHC) II, as assessed with microarray analysis. MHC II protein levels were also increased and inversely correlated with cognitive ability. Interestingly, the mild/moderate AD dementia cases also exhibited decreased number of T cells in the hippocampus and the cortex compared to controls. In conclusion, transition into AD dementia correlates with increased MHC II + microglia-mediated immunity and is paradoxically paralleled by a decrease in T cell number, suggesting immune dysfunction.

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Prevalence of Alzheimer’s disease in very elderly people

Cited by 172 publications

References 39 publications

Neuropathologic features associated with Alzheimer disease diagnosis

Neuropathologic features associated with Alzheimer disease diagnosis

Alzheimers and Dementia in the Oldest-Old: A Century of Challenges

Inflammatory changes parallel the early stages of Alzheimer disease

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