The rising tide of dementia worldwide.
- [Show abstract] [Hide abstract]
ABSTRACT: To investigate whether lower estimated glomerular filtration rate (eGFR) or chronic kidney disease (CKD) was associated with subsequent cognitive and instrumental activity of daily living (IADL) decline in a prospective cohort study. Prospective cohort study, followed for up to 4 years. General community. One thousand three hundred fifteen adults aged 55 and older from the Singapore Longitudinal Aging Study. Baseline data included eGFR levels, presence of CKD (eGFR < 60 mL/min per 1.73 m(2) ), and known confounders. Cognitive decline was defined as a drop of 2 or more points on the Mini-Mental State Examination (MMSE) and functional decline as a drop of 2 or more points in IADL score. Decreasing levels of eGFR and the presence of CKD were associated with greater odds of cognitive decline at follow-up independent of confounding risk factors in multivariate analyses: estimated 14% increment in odds of cognitive decline per 10 mL/min/1.73 m(2) decrease in eGFR (odds ratio = 1.94, 95% confidence interval = 1.23-3.05; P = .004 for CKD vs non-CKD). Similar associations were found in a cognitively normal subgroup (MMSE > 23) at baseline. In the whole sample, CKD, but not eGFR, was found to be significantly associated with higher risk of IADL decline. CKD in older persons was significantly associated with cognitive and functional decline. Future research should target the development and evaluation of strategies to delay or prevent cognitive decline and physical disability in elderly adults with impaired kidney function.Journal of the American Geriatrics Society 06/2012; 60(7):1208-14. · 4.22 Impact Factor
Article: The natural history of dementia.[Show abstract] [Hide abstract]
ABSTRACT: This review summarizes studies on the natural history of dementia with a focus on Alzheimer's disease and vascular dementia. Understanding the course of dementia is important not only for patients, caregivers, and health professionals, but also for health policy-makers, who have to plan for national resources needed in the management of an increasing number of dementia cases. From the available published data, the life expectancy of elderly people with dementia is shorter than that of non-demented elderly. Reports on survival after a diagnosis of dementia vary from 3 to 12 years. The wide variation is partly due to the diagnostic criteria used in the studies and the sites where they were conducted (i.e. hospitals, clinics, or homes). There is an apparent difference in survival between Alzheimer's disease patients with onset of illness before 75 years and those after 75 years: the younger patients have a longer life expectancy. However, there are conflicting data on survival (in years) comparing male and female patients and comparing patients of different ethnicities. For vascular dementia, published papers on life expectancy vary between 3 to 5 years. Vascular dementia appears to have a poorer prognosis than Alzheimer's disease. The stages of severity of dementia were compared in a follow-up of a sample of Alzheimer's disease patients in Singapore, and the mean duration of the mild phase (clinical dementia rating 1) was 5.6 years, the moderate phase (clinical dementia rating 2) was 3.5 years, and the severe phase (clinical dementia rating 3) was 3.2 years. At the various phases of the disease, the demand on health-care services and economic cost are different.Psychogeriatrics 09/2014; 14(3):196-201. · 1.22 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Early detection of dementia aims to improve treatment outcomes. However, poor perception and understanding of dementia are significant barriers. We aim to investigate the public's perception of dementia and identify variables associated with the different profiles of public perception. A custom-designed questionnaire was used to assess laypersons' knowledge and perception of dementia during a health fair at a public hospital in Singapore, a developed Asian nation. Out of a sample of 370 subjects, 32 declined to participate (response rate = 91.4%). Latent class analysis (LCA) was used to identify meaningful subgroups of subjects from significant associations with multiple indicators of dementia awareness. Multinomial logistic regression was performed exploring variables associated with each of the subgroups derived from LCA. The majority of the study participants were female (66.9%), 65 years or older (71.1%), and ethnic Chinese (88.1%). LCA classified the study participants into 3 subgroups: Class 1 (good knowledge, good attitude), Class 2 (good knowledge, poor attitude), and Class 3 (poor knowledge, poor attitude), in proportions of 14.28, 63.83, and 21.88%, respectively. Compared to other classes, participants with good knowledge and good attitude towards dementia (Class 1) were more likely to know someone with dementia and understand the effects of the disease, be married, live in private housing, receive higher monthly income, and not profess belief in Buddhism, Taoism, or Hinduism. Our results show that the public in Singapore may not be ready for screening initiatives and early dementia diagnosis. Education efforts should be targeted at lower socioeconomic groups, singles, and those of certain oriental religions.Dementia and geriatric cognitive disorders extra. 01/2012; 2(1):433-44.
www.thelancet.com Vol 372 August 9, 2008
in the general population, it is diffi cult to exclude chance
as an explanation for their fi ndings.
In today’s study, Vestergaard and colleagues tested
the hypothesis that febrile seizures are associated with
an increased risk of death, by examining mortality
data from a cohort of more than 1·6 million children,
including over 55 000 children with febrile seizures and
over 8000 deaths. They noted that in children who had a
febrile seizure, there was an increased risk of death in the
2 years after the fi rst febrile seizure, but that the absolute
risk of death was still very low. In a nested case-control
study, they attempted to fi nd more clinical information
than is usually available in registry data, through review
of medical records. They report that the increased risk of
death after febrile seizure was seen only in children with
complex febrile seizures and in those with underlying
Vestergaard and colleagues’ study again seems to
refute, for infants and children who have simple febrile
seizures, the idea of a shared cause between febrile
seizures and sudden death. Similar to previous studies,
most recently that of Kinney and colleagues, the new
study suggests there is a subset of children with febrile
seizures—notably those with complex features and
underlying neurological abnormalities—that might
warrant closer attention and follow-up.
Our grasp of the personal and public-health challenges
that dementia poses worldwide keeps evolving. A major
step is reported in today’s Lancet by Juan Llibre Rodriguez
and colleagues from the 10/66 Dementia Research
Group in a population-based study.1
Less than 40 years ago, Alzheimer’s disease was
lumped with Pick’s disease as a presenile dementia;
and cognitive decline, including extreme senility, was
supposedly part of a continuum of normal ageing. That
view became untenable when the numbers of elderly
people in developed countries mush roomed. Dementias
occur mainly in old people, doubling in prevalence
about every 5 years after 65 years of age in developed
countries2 and every 7 years in devel oping ones.
More recently, dementia research has posited mild
cognitive impairment, a curious and heterogeneous
condition. Some call it a disease, but others say that
makes it into a process that can be part of normal
ageing. Mild cognitive impairment is common in elderly
people and aff ects nearly one in four older than 70 years
of age.3 The condition does not neces sar ily lead to
dementia. By itself, it characteristically causes no sub-
stantial dysfunction, other than sub jective worry.
Llibre Rodriguez and colleagues studied rates of
dementia in elderly people in low-income and middle-
income countries. They found that the rates of dementia
varied widely between nations but tended to be higher
than previously thought; and rates in urban Latin America
(approaching 10%) resemble those in high-income
countries. Populations world wide are increasingly
ageing, so late-life dementias have far-reaching con-
sequences for health.
Dementia is rare in people younger than 65 years of
age, but incidence increases exponentially with age,
The rising tide of dementia worldwide
Department of Neurology, Children’s Hospital Boston, Boston,
MA 02115, USA
I declare that I have no confl ict of interest.
1 Vestergaard M, Giørtz Pedersen M, Østergaard JR, Bøcker Pedersen C,
Olsen J, Christensen J. Death in children with febrile seizures: a population-
based cohort study. Lancet 2008; 372: 457–63.
Consensus development conference on febrile seizures, National Institutes
of Health, May 19–21, 1980. Epilepsia 1981; 22: 377–81.
Nelson KB, Ellenberg JH. Predictors of epilepsy in children who have
experienced febrile seizures. N Engl J Med 1976; 295: 1029–33.
Off ringa M, Bossuyt PM, Lubsen J, et al. Risk factors for seizure recurrence
in children with febrile seizures: a pooled analysis of individual patient data
from fi ve studies. J Pediatr 1994; 124: 574–84.
Lennox MA, Sibley WA, Zimmerman HM. Fever and febrile convulsions in
kittens: a clinical, electroencephalographic, and histopathologic study.
J Pediatr 1954; 45: 179–90.
Sunderland R, Emery JL. Febrile convulsions and cot death. Lancet 1981;
Hoyert DL, Arias E, Smith BL, Murphy SL, Kochanek KD. Deaths: fi nal data
for 1999. Natl Vital Stat Rep 2001; 49: 1–113.
Mathews TJ, Menacker F, MacDorman MF. Infant mortality statistics from
the 2002 period: linked birth/infant death data set. Natl Vital Stat Rep
2004; 53: 1–29.
Moon RY, Horne RS, Hauck FR. Sudden infant death syndrome.
Lancet 2007; 370: 1578–87.
10 Nelson KB, Ellenberg JH. Prognosis in children with febrile seizures.
Pediatrics 1978; 61: 720–27.
11 Vestergaard M, Basso O, Henriksen TB, Ostergaard J, Olsen J. Febrile
convulsions and sudden infant death syndrome. Arch Dis Child 2002;
12 Kinney H, Armstrong D, Chadwick A, et al. Sudden death in toddlers
associated with developmental abnormalities of the hippocampus: a report
of fi ve cases. Pediatr Dev Pathol 2007; 10: 208–23.
July 28, 2008
See Articles page 464
www.thelancet.com Vol 372 August 9, 2008 431
especially when older than 80 years.4 Interestingly, the
eff ect of dementia on survival is not uniform. The earlier
its onset, the more Alzheimer’s disease causes excess
mortality. Diff erences in survival between aff ected and
unaff ected populations decrease progressively with
age. In one study, for individuals in Seattle with onset
after age 90 years, survival diff erences were minor.5
More over, dementia is not an inevitable consequence
of old age as shown by a well-described Belgian woman
who survived until aged 115 years with good cognitive
function, no preclinical indications of Alzheimer’s disease,
and almost no neuro degenerative changes on examin-
ation of the brain.6
The rising tide of late-life dementia is both a triumph
of public health and an opportunity. Increased worldwide
prevalence refl ects gains in life expectancy, perhaps
made more evident in present knowledge-based
societies.7 Cognitive skills are probably more essen tial
for survival—and sustain wellbeing better—in cities,
where people are increasingly concentrated. Because
the rates rise considerably in late old age, delaying the
onset of functional impairment would represent true
prevention—or at least compression of morbidity.8
Data from the population-based Health and Retirement
Study suggest that rates of cognitive impairment are
decreasing in the USA,9 from 12·2% in those older than
70 years in 1993 to 8·7% in 2002. The interval between
onset of substantial cogni tive decline and death seems
to have decreased too, suggesting a compression of
cognitive morbidity. The change in rates was mainly
associated with higher education and wealth, and
probably with improved control of cardiovascular risk.
Progress made to achieve higher levels of education
worldwide and better general health and control of
cardiovascular risk factors could help postpone dis-
ease processes, delaying dementia as lifespan becomes
increasingly genetically determined; as environ mental
factors are recognised and controlled, genetic factors
become more important. Education of successive
generations might multiply the delay of dementia.10
Education of women might help protect their children
from developing late-life dementia.11
Llibre Rodriguez and colleagues suggest that in many
cultures, with high degrees of support and respect for
older people, relatives might not perceive dementia as a
problem. Similarly, one could debate the merits of turning
mild cognitive impairment into a disease. The current
focus on eff orts to better understand mild cognitive
impairment will probably have less value than many hope
for the public’s health. Secondary prevention trials in
individuals with mild cognitive impairment designed to
test whether dementia can be delayed are an appropriate
area for research. However, the risk of late-life cognitive
decline and processes causing dementia probably orig-
inates throughout an individual’s lifespan.
Similarly to the degenerative coronary artery disease
in young US soldiers who died in the Korean confl ict
in the 1950s,12 neuropathological changes and subtle
diff erences in cognition occur early in life, well before
clinical disease manifests. So eff orts that promote general
health (improved education and nutrition, control
of cardiovascular risk, and physical and cognitively
engaging activities) could delay progression of the
degenerative changes of Alzheimer’s disease in the brain
and vascular diseases.13 Growing evidence also supports
brain plasticity,14 contradicting the long-held notion that
damaged brain tissue cannot regenerate or be restored.
Brain plasticity implies that opportunities exist to modify
changes in the brain related to age and even to disease.
The 10/66 study will provide unique opportunities
to explore environmental eff ects on the ageing process
in the brain. Llibre Rodriguez and colleagues rightly
emphasise the formidable challenges of measuring
cognition and its eff ects on function across cultures.
We applaud their focus on actual function and especially
functional impairment, which leads to suff ering and
The printed journal
includes an image merely
www.thelancet.com Vol 372 August 9, 2008
dependency. We should work towards letting more of
the world’s people experience long life as a reward for
their many years of life—not as punishment for the
triumphs of modern medicine and public health.
*Eric B Larson, Kenneth M Langa
Group Health Center for Health Studies, Seattle, WA 98101, USA
(EBL); and Internal Medicine, University of Michigan, Ann Arbor,
MI, USA (KML)
We thank Rebecca Hughes for help with editing this Comment. We declare that
we have no confl ict of interest.
1 Llibre Rodriguez JJ, Ferri CP, Acosta D, et al, for the 10/66 Dementia
Research Group. Prevalence of dementia in Latin America, India, and China:
a population-based cross-sectional survey. Lancet 2008; published online
July 28. DOI:10.1016/S0140-6736(08)61002-8.
Lobo A, Launer LJ, Fratiglioni L, et al, for the Neurologic Diseases in the
Elderly Research Group. Prevalence of dementia and major subtypes in
Europe: a collaborative study of population-based cohorts.
Neurology 2000; 54 (suppl 5): 4–9.
Plassman BL, Langa KM, Fisher GG, et al. Prevalence of cognitive impairment
without dementia in the United States. Ann Intern Med 2008; 148: 427–34.
4 Kukull WA, Higdon R, Bowen JD, et al. Dementia and Alzheimer disease
incidence: a prospective cohort study. Arch Neurol 2002; 59: 1737–46.
Larson EB, Shadlen MF, Wang L, et al. Survival after diagnosis of
Alzheimer’s disease. Ann Intern Med 2004; 140: 501–09.
den Dunnen WF, Brouwer WH, Bijlard E, et al. No disease in the brain of
a 115-year-old woman. Neurobiol Aging 2008; 29: 1127–32.
Drucker PF. The next society. Economist Nov 3, 2001: 2–20.
Fries JF. Aging, natural death, and the compression of morbidity.
N Engl J Med 1980; 303: 130–35.
Langa KM, Larson EB, Karlawish JH, et al. Trends in the prevalence and
mortality of cognitive impairment in the United States: 1993–2004.
Alzheimer Dement 2008; 4: 134–44.
10 Moceri VM, Kukull WA, Emanual I, et al. Using census data and birth certifi cates
to reconstruct the early-life socioeconomic environment and the relation to
the development of Alzheimer’s disease. Epidemiology 2001; 12: 383–89.
11 Rogers M, Plassman B, Kabeto M, et al. Parental education and late-life
dementia in the United States. J Geriatr Psychiatry Neurol (in press).
12 Enos WF Jr, Beyer JC, Holmes RH. Pathogenesis of coronary disease in
American soldiers killed in Korea. JAMA 1955; 158: 912–14.
13 Moceri VM, Kukull WA, Emanuel I, et al. Early-life risk factors and the
development of Alzheimer’s disease. Neurology 2000; 54: 415–20.
14 Gould E. Learning enhanced adult neurogenesis in the hippocampal
formation. Nat Neurosci 1999; 2: 260–65.
The Wakley Prize 2008
Thomas Wakley, who founded The Lancet in 1823 when
he was only 28 years old, was a swashbuckling larger-
than-life character. The annual Wakley Prize is named
in his honour and seeks to exemplify the spirit of a
man who was passionately committed to reforming
the practice of medicine and to improving the lives of
patients. The prize is given to the best essay on a topic
of international health importance. Last year’s winner,
in telling the story of a Cree man living with diabetes in
an Aboriginal village in northern Saskatchewan, Canada,
illuminated how medicine and culture can sometimes
fi nd themselves at odds, and how, or whether, those
diff erences can be reconciled.1 In a larger sense, the
essay was about the diffi culty of truly knowing another.
We are looking for fresh new writing that critically
examines these and other challenges in contemporary
medicine. Essays must be submitted before Oct 31,
2008, and may not exceed 2000 words. The winner will
be determined by Lancet editors (who will judge each
entry without knowing the author’s identity), and will
receive £2000 and publication in the fi nal issue of the
year. The contest is open to anyone working or training
in a health-related fi eld. Essays must be submitted
through The Lancet’s electronic submission system, with
Wakley Prize essay specifi ed as the article type.
The Lancet, New York, NY, USA
1 Mateen FJ. Smoking the pipe of peace. Lancet 2007; 370: 2170–71.
To submit an essay go to