Table 1.
Principal population-based studies on the association of deficit accumulation/multidimensional operational definition of frailty, frailty instruments, and physical/phenotypic/biological operational definition of frailty with late-life cognitive impairment and decline, mild cognitive impairment (MCI), dementia, Alzheimer's disease (AD), and other different cognitive outcomes.
| References | Study design and sample | Frailty and cognitive assessment | Principal results |
|---|---|---|---|
| Buchman et al., 2007 | Population-based, longitudinal study (3 years); 823 older persons (mean age: 80.4 years) without dementia who participated in the Rush Memory and Aging Project | Physical frailty phenotype operalizionated slightly modifying the CHS criteria and based on four frailty components. Diagnoses of AD and DLB were made according to the NINCDS-ADRDA and the Report of the Consortium on DLB International Workshop. The MMSE was used to describe the cohort, while scores on other 19 neuropsychological tests were used to create a composite measure of global cognitive function. The CIM was used for diagnostic classification purposes only | Both baseline level of frailty and annual rate of change in frailty were associated with an increased risk of incident AD. Furthermore, the level of frailty and rate of change in frailty were also associated with the rate of cognitive decline |
| Buchman et al., 2008 | Population-based, longitudinal study; brain autopsies from 165 deceased participants from the Rush Memory and Aging Project | Physical frailty phenotype operalizionated slightly modifying the CHS criteria and based on four frailty components. Diagnoses of AD and DLB were made according to the NINCDS-ADRDA and the Report of the Consortium on DLB International Workshop criteria. Neuropathological measures of AD pathology, Lewy bodies, and cerebral infarcts were also obtained | Physical frailty proximate to death was related to level of AD pathology on post-mortem examination but was not related to the presence of cerebral infarcts or Lewy body disease. This association was similar in persons with and without dementia |
| Samper-Ternent et al., 2008 | Population-based, longitudinal study (10 years); 1370 non-institutionalized Mexican American men and women aged 65 years and older from the H-EPESE with a MMSE ≥ 21 at baseline | Physical frailty phenotype operalizionated slightly modifying the CHS criteria based on four frailty components and excluding physical activity and MMSE | A statistically significant association between frailty and subsequent decline in cognitive function over a 10-years period was found in older Mexican Americans |
| Avila-Funes et al., 2009 | Population-based, cross-sectional and longitudinal study (4 years); 6030 older individuals aged 65–85 years from the Three-City Study | Physical frailty phenotype operalizionated slightly modifying the CHS criteria, MMSE, and IST. Diagnosis of dementia according to the DSM-IV criteria | Frail individuals with cognitive impairment have a higher risk of IADL and ADL disability and of incident hospitalization and dementia than subjects with none of these conditions, even after adjusting for potentially confounding variables |
| Boyle et al., 2010 | Population-based, longitudinal study (12 years); 761 older persons (mean age: 79 years) without cognitive impairment at baseline who participated in the Rush Memory and Aging Project | Physical frailty phenotype operalizionated slightly modifying the CHS criteria and based on four frailty components. Diagnoses of AD and MCI were made according to the NINCDS-ADRDA criteria and CSHA clinical criteria. The MMSE was used to describe the cohort, while scores on other 19 neuropsychological tests were used to create a composite measure of global cognitive function. The CIM was used for diagnostic classification purposes only | Higher level of physical frailty predicted the development of MCI and is associated with an accelerated rate of cognitive decline in older persons |
| Mitnitski et al., 2011a | Population-based, longitudinal study (5 years); 9266 individuals of the CSHA sample subjects aged 75.8 ± 7.1 years | CSHA Frailty Index and 5-years change in errors on 3MS grouped into categories of 3 | Frailty at baseline associated with cognitive change in men and women |
| Mitnitski et al., 2011b | Population-based, longitudinal study (5 years); 2305 individuals from the CSHA sample of subjects aged 83.1 ± 6.9 years | CSHA Frailty Index, CSHA Clinical Frailty Scale, CHS frailty phenotype and 5-years change in errors on 3MS grouped into categories of 3 | All measures of frailty at baseline associated with cognitive decline |
| Song et al., 2011 | Population-based, longitudinal study (5 and 10 years); 5909 individuals from the CSHA aged 65 years and older | Frailty Index of “non-traditional” risk factors for dementia and diagnosis of dementia according to the DSM-III-R and diagnosis of AD according to NINCDS-ADRDA criteria | Frailty at baseline was associated with the incidence of AD and dementia of all types over 5- and 10-year intervals |
| Solfrizzi et al., 2012 | Population-based, longitudinal study (3 and 7 years); 2581 individuals from the ILSA sample of 5632 subjects aged 65–84 years | Physical frailty phenotype operalizionated slightly modifying the CHS criteria and diagnosis of dementia according to the DSM-III-R, NINCDS-ADRDA, and ICD-10 criteria | Lower cognition was associated with physical frailty. Frail demented patients were at higher risk of all-cause mortality over 3- and 7-years follow-up periods, but not of disability |
| Cano et al., 2012 | Population-based, longitudinal study (10 years); 1815 Mexican American men and women aged 67 years and older from the H-EPESE | Physical frailty phenotype operalizionated slightly modifying the CHS criteria and MMSE > 21 | As MMSE score declined over time, the percent of frail individuals increased in a linear fashion. Frailty and cognitive impairment are independent risk factors for mortality after controlling for all covariates. When both cognitive impairment and frailty were added to the model, hazard ratio for individuals with cognitive impairment was no longer statistically significant |
| Avila-Funes et al., 2012 | Population-based, longitudinal study (7 years); 5480 older individuals aged 65–85 years from the Three-City Study | Physical frailty phenotype operalizionated slightly modifying the CHS criteria, MMSE, and IST. Diagnosis of dementia according to the DSM-IV criteria and VaD according to the NINDS-AIREN criteria | Frailty was marginally associated with greater risk of all types of dementia and was not associated with incident AD, but frailty status was independently associated with incident VaD |
| Solfrizzi et al., 2013 | Population-based, longitudinal study (3.5 years); 2581 individuals from the ILSA sample of 5632 subjects aged 65–84 years | Physical frailty phenotype operalizionated slightly modifying the CHS criteria and diagnosis of dementia according to the DSM-III-R, NINCDS-ADRDA, and ICD-10 criteria | Over a 3.5-years follow-up, frailty syndrome was associated with a significantly increased risk of overall dementia and, in particular, VaD, while the risk of AD or other types of dementia did not significantly change in frail individuals in comparison with subjects without frailty syndrome |
| Gray et al., 2013 | Population-based, longitudinal study (6.5 years); 2619 individuals from the Adult Changes in Thought (ACT) study sample of subjects aged 65 years and older | Physical frailty phenotype operalizionated with the CHS criteria and diagnosis of dementia according to the DSM-IV, diagnosis of possible and probable AD according to NINCDS-ADRDA criteria. Non-AD dementia consisted of all dementias not classified as possible or probable AD | Frailty was associated with higher risk of developing non-AD dementia but not AD. Although frailty was not associated with all-cause dementia in the entire sample, an association did exist in participants with higher cognitive scores |
CHS, Cardiovascular Health Study; DLB, dementia with Lewy bodies; NINCDS-ADRDA, National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association; MMSE, Mini Mental State Examination; CIM, Complex Ideational Material; EPESE, Established Population for the Epidemiological Study of the Elderly; IST, Isaac Set Test; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders-IV; IADL, instrumental activities of daily living; ADL, activities of daily living; CSHA, Canadian Study of Health and Aging; 3MS, modified Mini Mental State Examination; DSM-III-R, Diagnostic and Statistical Manual of Mental Disorders-III revised; ICD-10, International Statistical Classification of Diseases and Related Health Problems, 10th revision; ILSA, Italian Longitudinal Study on Aging; VaD, vascular dementia; NINDS-AIREN, National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences.