Aging and the Occurrence of DementiaFindings From a Population-Based Cohort With a

Large Sample of Nonagenarians (1999)

Eva von Strauss, MSc; Matti Viitanen, PhD; Diana De Ronchi, MD; et al

Context - In spite of numerous studies on the occurrence of dementia, many questions remain,
such as the relation between age, aging, and dementing disorders. This question is relevant
both for understanding the pathogenetic mechanism of the dementias and for the public
health prospective because of the increasing number of 85-year-old or older persons in our
population.

Objective - To estimate the occurrence of dementia in the very old, including nonagenarians, in
relation to age, gender, and different dementia types.

Design - An epidemiological survey where all participants were clinically examined by

physicians, assessed by psychologists, and interviewed by nurses. The Diagnostic and Statistical
Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria for dementia were
followed. A category of "questionable dementia" was added when all criteria were not
fulfilled. A double diagnostic procedure was used for all subjects.

Setting - Community-based population, including all inhabitants of 2 areas in central

Stockholm, Sweden (N=1848).

Participants - Of the 1848 subjects in the study population, 168 (9.1%) had died and 56 (3%)
moved before examination. Of the remaining subjects, 1424 (87.7%) were examined, and the
refusal rate was 12.3%.

Main Outcome Measures - Age- and gender-specific prevalence figures, and gender- and
education-adjusted odds ratios were used.

Results - At the end of the diagnostic procedure, 358 clinically definite cases of dementia and
101 questionable cases of dementia were identified. Alzheimer disease (AD) contributed to
76.5%, and vascular dementia (VaD) to 17.9%. The prevalence of dementia increases from 13%
in the 77- to 84-year-old subjects to 48% among persons 95 years and older (from 18% to 61%
when questionable cases were included). The odds ratio for subjects 90 to 94 years and 95
years and older in comparison with 77- to 84-year-old subjects was 3.7 (95% confidence
interval [CI], 2.7-5.1) and 6.5 (95% CI, 3.9-10.8) for dementia, 4.8 (95% CI, 3.3-7.0) and 8.0 (95%
CI, 4.6-14.0) for persons with AD, 2.3 (95% CI, 1.3-4.2) and 4.6 (95% CI, 1.9-11.2) for VaD,
respectively.

Conclusions - Dementia prevalence continues to increase even in the most advanced ages. This
increase is especially evident among women and is more clear for AD. We believe that our
prevalence data reflect the differential distribution of dementia risk.

The Relative Frequency of "Dementia of Unknown Etiology" Increases With Age and Is Nearly
50% in Nonagenarians (2000)

Howard A. Crystal, MD; Dennis Dickson, MD; Peter Davies, PhD; et al

Context  With the recent change in pathological criteria for Alzheimer disease (AD), a group of
patients has emerged who do not meet pathological criteria for any well-characterized
degenerative dementias. Whether these unclassified patients have vascular dementia or some
other form of dementia is not known.

Objective  To determine the clinical characteristics, pathological substrate, and relative

frequency of dementia not caused by well-characterized degenerative dementias.

Design/Setting  Clinicopathological study of a prospectively observed sample of elderly

nondemented and demented subjects recruited from our urban community.

Methods  In our series of 128 subjects with prospective neuropsychological evaluations as well
as neuropathology, we identified 35 clinically nondemented subjects and 20 demented
patients who did not meet pathological criteria for well-characterized degenerative dementias
such as AD or dementia with Lewy bodies. The 20 demented patients were grouped together
under the term dementia of unknown etiology (DUE). We compared clinical, genetic,
neuropsychological, pathological, and neurochemical characteristics of the nondemented
group, patients with DUE, and 28 patients with AD and no other pathological abnormality.

Results  Mean age at death for patients with DUE was 89.1 ± 5.8 years compared with 79.9 ±
11.4 years for AD (P<.001). Patients with AD and DUE did not differ in sex, risk factors,
apolipoprotein E genotype, neuropsychological features, or neurological features.
Hippocampal sclerosis (in 11 patients with dementia and no controls) and
leukoencephalopathy (in 7 patients with dementia and 1 control) were associated with
cognitive impairment; other vascular markers were not. Dementia of unknown etiology
accounted for 5% of all cases of dementia among patients dying in their 70s, 21% for patients
dying in their 80s, and 48% for patients dying in their 90s.

Conclusions  A significant percentage of demented patients older than 80 years do not meet
pathological criteria for AD or dementia with Lewy bodies. Hippocampal sclerosis and
leukoencephalopathy are common in these patients but rare in clinically nondemented
subjects.

Different Classification Systems Yield Different Dementia Occurrence among Nonagenarians

and Centenarians (2004)

Pioggiosi P.a · Forti P.b · Ravaglia G.b · Berardi D.a · Ferrari G.a · De Ronchi D.a

Literature data consistently show different prevalence estimates of dementia when different
classification systems are used in the same population. Very few data are available for the
oldest old of the elderly. We investigated the occurrence of dementia among 34
nonagenarians and centenarians according to four classification systems: the American
Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, third edition
revised (DSM-III-R) and fourth edition (DSM-IV), the World Health Organization’s International
Classification of Diseases, 10th revision (ICD-10), and the Cambridge Examination for Mental
Disorders of the Elderly (CAMDEX). Cognitive functioning, work, social function and
independence in activities of daily living were evaluated by using an extensive
neuropsychological examination. The prevalence (95% CI) of dementia was the following:
47.1% (95% CI 30.3–63.8) with the DSM-III-R criteria, 41.2% (95% CI 24.6–57.7) with the DSM-
IV criteria, 29.4% (95% CI 14.1–44.7) with the ICD-10 criteria and 38.2% (95% CI 21.9–54.6)
with the CAMDEX. The factors that best predicted disagreement between DSM-III-R and DSM-
IV were calculation impairment and the presence or absence of personality changes. DSM-III-R
and ICD-10 were differentiated by the weight given to executive functions that all have to be
impaired according to ICD-10, whereas progressive deterioration differentiated CAMDEX from
DSM-III-R. It should be noted that although the DSM-III-R diagnoses differ by a factor of 1.6
times from the ICD-10 and 1.2 times from the CAMDEX diagnoses, we are speaking about
dementia, which is very frequent in nonagenarians and centenarians. Moreover, with regard to
public health, an estimation of the number of subjects who will lose their autonomy is rather
more useful and informative than simple prevalence figures of dementia by itself. In this light,
classification systems, such as the ICD-10, that do not include impairment of social function as
a criterion for assessing dementia become less adequate.

The prevalence of dementia in 95 year olds (2004)

Anne Börjesson-Hanson, Eva Edin, Thorsteinn Gislason, Ingmar Skoog

The authors determined the prevalence of dementia in 338 (response rate 65%) 95-year-old
persons, living in Göteborg, Sweden, and compared the result with a previously examined
population sample of 85 year olds. The prevalence of dementia according to the Diagnostic
and Statistical Manual of Mental Disorders (3rd rev. ed) was higher in women (55%) than in
men (37%) at age 95, and the proportion of mild dementia and vascular dementia was lower in
95 than in 85 year olds.

A Longitudinal Study of the Mini‐Mental State Examination in Late Nonagenarians and Its
Relationship with Dementia, Mortality, and Education (2017)

Johan Skoog MSc Kristoffer Backman MSc Mats Ribbe MD Hanna Falk PhD Pia Gudmundsson
PhD Valgeir Thorvaldsson PhD Anne Borjesson‐Hanson MD, PhD Svante Ostling MD, PhD Boo
Johansson PhD Ingmar Skoog MD, PhD

Objectives

To examine level of and change in cognitive status using the Mini‐Mental State Examination
(MMSE) in relation to dementia, mortality, education, and sex in late nonagenarians.

Design

Three‐year longitudinal study with examinations at ages 97, 99, and 100.

Setting

Trained psychiatric research nurses examined participants at their place of living.

Participants
A representative population‐based sample of 97‐year‐old Swedes (N = 591; 107 men, 484
women) living in Gothenburg, Sweden.

Measurements

A Swedish version of the MMSE was used to measure cognitive status. Geriatric psychiatrists
diagnosed dementia according to the Diagnostic and Statistical Manual of Mental Disorders,
Third Edition, Revised. Mixed models were fitted to the data to model the longitudinal
relationship between MMSE score and explanatory variables.

Results

Individuals with dementia between age 97 and 100 had lower mean MMSE scores than those
without dementia. Those who died during the 3‐year follow‐up had lower MMSE scores than
those who survived. MMSE scores at baseline did not differ between those without dementia
and those who developed dementia during the 3‐year follow‐up. Participants with more
education had higher MMSE scores, but there was no association between education and
linear change.

Conclusion

MMSE score is associated with dementia and subsequent mortality even in very old
individuals, although the preclinical phase of dementia may be short in older age. Level of
education is positively associated with MMSE score but not rate of decline in individuals
approaching age 100.

Dementia-free centenarians (2004)

ThomasPerls

Background

A small percentage of centenarians, about 15–25%, are functionally cognitively intact. Among
those who are not cognitively intact at 100, approximately 90% delayed the onset of clinically
evident impairment at least until the average age of 92 yr.

Objective

To review current and past findings related to the prevalence and incidence of dementia
amongst the exceptionally long-lived.

Methods

Findings from the various centenarian studies, world-wide, are reviewed.

Results

Neuropsychological and neuropathological correlations thus far suggest that there are
centenarians who demonstrate no evidence of neurodegenerative disease. There also appear
to be centenarians who despite the substantial presence of neuropathological markers of
Alzheimer's disease did not meet clinical criteria for having dementia, thus suggesting the
existence of cognitive reserve. Epigenic studies suggest a significant familial component to
these survival advantages.

Conclusion

Centenarians are of scientific interest as a human model of relative resistance to dementia.

Dementia in nonagenarians. Systematic review of population-based studies with Spanish

data (2008)

Carrillo-Alcalá ME, Bermejo-Pareja F

INTRODUCTION: Ageing is associated with the quasi exponential getting up of dementia

prevalence and incidence until 85 years, but the data in the oldest-old are controversial. AIM.
Systematic review of population based studies that analyze prevalence and incidence of
dementia in the oldest-old, specifically in nonagenarians. PATIENTS AND METHODS: Systematic
review in Medline database of population based surveys describing prevalence or incidence in
older than 90, published from 1989. 459 papers were identified, but of the 170 population-
based detailed reviewed, 41 studies accomplished the inclusion criteria (Pamplona, Gerona
and NEDICES Study are included). RESULTS: The dementia prevalence described in
nonagenarians has a range of 25-54%. The dementia incidence in older than 90 has a range of
47-174 cases per 1,000 people/year, being greater in females. In the oldest-old a variable
prevalence and incidence of dementia was described in the selected studies. Some authors
consider that exist an exponential increase in the dementia prevalence and another ones
indicate a slowing of growth in nonagenarians. CONCLUSIONS: This review is concordant with a
persistent not exponential increase in prevalence and incidence of dementia in nonagenarians.

Dementia in the oldest old (2013)

Zixuan Yang, Melissa J. Slavin & Perminder S. Sachdev

People over the age of 90 years—the oldest old—are the fastest growing sector of the
population. A substantial proportion of these individuals are affected by dementia, with major
implications for the individual as well as society. Research on dementia in the oldest old is
important for service planning, and the absence of dementia at this exceptional old age may
serve as a model of successful ageing. This Review summarizes population-based
epidemiological studies of dementia and its underlying neuropathology in nonagenarians and
centenarians. The available data, although somewhat limited, show an age-specific and sex-
specific profile of dementia status in very late life, resulting from a variety of neuropathologies
that often co-occur. Extensive overlap in neuropathology between cognitively normal and
cognitively impaired individuals is evident despite challenges to gathering data particular to
this population. A complex picture is emerging of multiple pathogenetic mechanisms
underlying dementia, and of the potential risk and protective factors for dementia that interact
with genetics and lifestyle in normal and exceptional cognitive ageing.

Alzheimer's and Dementia in the Oldest-Old: A Century of Challenges (2006)

Kawas, Claudia H.; Corrada, Maria M.

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.