Brief Report  |   November 2017
Frailty Phenotype and Neuropsychological Test Performance: A Preliminary Analysis
Author Notes
  • From the Department of Geriatrics and Gerontology at the New Jersey Institute for Successful Aging at the Rowan University School of Osteopathic Medicine in Stratford, New Jersey (Drs Ginsberg, Powell, Chopra, Cavalieri, and Libon and Mr Patel), and the Department of Psychology at Rowan University in Glassboro, New Jersey (Ms Emrani and Dr Libon). 
  • Financial Disclosures: None reported. 
  • Support: None reported. 
  •  *Address correspondence to Terrie B. Ginsberg, DO, Department of Geriatrics and Gerontology, New Jersey Institute for Successful Aging, Rowan University School of Osteopathic Medicine, 42 E Laurel Rd, Ste 1800, Stratford, NJ 08084-1338. E-mail:
Article Information
Geriatric Medicine / Neuromusculoskeletal Disorders
Brief Report   |   November 2017
Frailty Phenotype and Neuropsychological Test Performance: A Preliminary Analysis
The Journal of the American Osteopathic Association, November 2017, Vol. 117, 683-687. doi:
The Journal of the American Osteopathic Association, November 2017, Vol. 117, 683-687. doi:

Context: Frailty is a common problem that affects adults older than 65 years. Correlations between the frailty phenotype and neuropsychological impairment have not been thoroughly researched.

Objective: To examine the association between frailty phenotype, neuropsychological screening test results, and neuropsychological domains known to characterize patients with mild cognitive impairment and dementia.

Methods: This retrospective medical record analysis consisted of ambulatory patients aged 65 years or older seen in an outpatient geriatric practice. All patients were assessed with the Montreal Cognitive Assessment (MoCA). A portion of those patients also underwent a comprehensive neuropsychological evaluation that assessed executive control, naming/lexical access, and declarative memory expressed as 3 neuropsychological index scores. Frailty phenotype was determined using criteria by Fried et al.

Results: Simple correlation found that lower MoCA test scores were associated with a higher level of frailty (r=−0.34, P<.032). Regression analyses found that greater frailty was associated with worse performance on tests that assessed executive control and working memory (backward digit span; r2=0.267; β=−0.517; P<.011) and delayed recognition memory (r2=0.207; β=−0.455; P<.025).

Conclusion: A correlation was found between frailty and neuropsychological impairment, which suggests that frailty may be a potential indicator for the emergence of mild cognitive impairment and dementia.

Frailty is a well-known clinical syndrome and comprises age-related comorbidities that can result in physiological decline,1,2 disability, and hospitalization.2 Frailty is defined using 5 clinical characteristics determined by Fried et al3: unintentional weight loss, weakness, exhaustion, slowness, and low physical activity. Using these criteria, frailty is defined when 3 of the 5 characteristics are present, and prefrailty is defined when 1 or 2 of these characteristics are present. Fried at al3 suggested that frailty is associated with an increased risk of medical comorbidities that may lead to disability, hospitalization, and physiological decline. Other researchers have determined that frailty is associated with institutionalization,4,5 impaired instrumental activities of everyday living, depression, and self-described degree of social disconnection.6 
Research has called attention to cognitive frailty,7,8 a condition that describes the coexistence of neuropsychological deficits in clinically frail patients, with some suggestion that neuropsychological impairment should be an additional parameter used to characterize frailty. A large epidemiologic study9 examined community-dwelling persons aged 65 to 95 years and noted that neuropsychological impairment (measured by activities of daily living and instrumental activities of daily living) was found in participants with prefrailty and frailty. In 2 reviews,2,10 cognitive impairment was present in people with prefrailty and frailty. 
Mild cognitive impairment (MCI) is believed to be a transitional state that can eventually lead to dementia.11 Among patients with MCI, recent investigations have linked the presence of frailty with poor performance on neuropsychological measures, including the Mini Mental State Evaluation and Clinical Dementia Rating Scale.12,13 Boyle et al14 found that physical frailty is associated with an increased risk of MCI; however, the relationship between frailty status and specific neuropsychological deficits has yet to be examined. The goal of the present study was to assess whether frailty is linked to specific neuropsychological deficits. 
A retrospective medical record analysis was conducted in patients who presented to an outpatient geriatric clinic for medical care and were examined by a board-certified geriatrist (T.B.G. or L.P.) from June 2016 through May 2017. Inclusion criteria were age 65 years or older and accompaniment by a knowledgeable family member. Patients were excluded if they had a history of medical illness (eg, cancer, epilepsy, multiple sclerosis). Institutional review board approval was obtained, and research was conducted consistent with the Declaration of Helsinski. 
Frailty was assessed as part of patients’ overall medical evaluation. Routine serum laboratory assessment was ordered, and the Montreal Cognitive Assessment15 (MoCA) was administered. A comprehensive neuropsychological evaluation was performed when the patient or caregiver was concerned about possible neurocognitive disorders. 
Frailty Assessment
Patients were considered frail if they met more than 3 of the frailty characteristics defined by Fried et al3 and were considered prefrail if they met 1 or 2 of the characteristics. Patients who met the weight loss characteristic reported recent, unintentional weight loss of at least 3 kg and had a body mass index less than 21 kg/m2. Exhaustion was self-reported (eg, “I felt that everything I did was an effort,” “I could not get going”). Weakness was determined by a grip strength test stratified by sex and body mass index quartiles. The slowness characteristic was met if a patient was in the lowest quintile in a timed, 6-meter walking test stratified by sex and height. Low physical activity was based on the short version of the Minnesota Leisure Time Activity questionnaire. 
Comprehensive Neuropsychological Assessment
Executive control of the participants who underwent a comprehensive neuropsychological evaluation was assessed with serial order recall from a backward digit-span test,16,17 in which the total number of digits correctly recalled in accurate backward serial order was tallied (ie, total number of correct digits in serial-order] / [total possible correct numbers] × 100) along with tests of letter fluency,18 in which participants were given 60 seconds to generate words, excluding proper nouns, beginning with a specified letter. The dependent variable was the number of responses summed across each letter. 
Naming/lexical access was assessed with a test of semantic fluency19 and the 60-item version of the Boston Naming Test.20 The dependent variables derived from both tests were the number of correct responses, excluding perseverations and intrusion errors. 
Verbal declarative memory was assessed with the mental status version of the California Verbal Learning Test.21 After a delay, both free recall and recognition were assessed. The dependent variables were delay-free recall and recognition standard scores. 
Neuropsychological indices were obtained using grand means and SDs obtained from the total sample. All test results were expressed as z scores. Tests within each neurocognitive domain were averaged to create executive, naming/lexical access, and declarative memory index scores. 
Statistical Analysis
Because of the modest sample size, correlation and regression analyses were used to assess the relationship between neuropsychological test performance and total frailty obtained from participants. Simple correlation assessed the relationship between frailty and MoCA test performance. A stepwise linear regression analysis was conducted, in which total frailty was the dependent variable, and the 3 neuropsychological index scores were the independent variables. Statistical significance was defined as P<.05. 
Fifty-one patients were included in the study. The mean (SD) age was 78.06 (6.61) years. Of the 51 patients, 6 (12%) did not meet any frailty criteria, 25 (49%) met the criteria for prefrailty, and 20 (39%) met the criteria for frailty. The mean (SD) MoCA score was 21.81 (5.96). The simple correlation between MoCA test performance and frailty was significant (r=−0.340, P<.032), such that greater frailty was associated with worse MoCA test performance. 
Twenty-two patients received a comprehensive neuropsychological evaluation. The step-wise regression with total frailty as the dependent variable and the 3 neuropsychological index scores as the independent variables was statistically significant. The executive control index entered the model first and accounted for 29.9% of variance (R=0.547; r2=0.299; F1,22=9.38; P<.006; β=−.536; P<.003); this calculation was followed by the declarative memory index, which accounted for an additional 17% of the model (R=0.682; r2=0.465; F1,22=5.75; P<.018; β=−.408; P<.018) Lower scores on both neuropsychological indices were associated with increased frailty. 
Follow-up step-wise regression analyses were conducted to assess which executive and declarative memory parameters were most significantly associated with frailty. In these analyses, only backward digit span performance (R=0.517; r2=0.267; F1,22=8.02; P<.010; β=−.517; P<.011) and the California Verbal Learning mental status test recognition score (R=0.455; r2=0.207; F1,22=5.75; P<.025; β=−.455; P<.025) entered the model. Low scores on the backward digit span and recognition memory tests were both associated with increased frailty. 
No statistically significant correlations were found between serum laboratory values and MoCA scores or neuropsychological test performance. 
A 2014 report22 noted that by the year 2050, the US population aged 65 years or older is estimated to grow to 83.7 million, approximately double the current population of people in that age group (43.1 million). This estimation is a clarion call for greater awareness of medical syndromes that affect older people. As the population ages, frailty is likely to become an increasingly pertinent problem. Thus, the importance of assessing frailty in older persons revolves around identifying and potentially managing comorbid factors that place an individual at risk for physical decline and disability. Neuropsychological functioning has emerged as a likely contributing factor in the development of frailty, and there is now interest in assessing how frailty is associated with specific types of neuropsychological impairment. Consistent with research,14,23 the current study found that lower MoCA test scores were associated with increased frailty. 
Among patients who were evaluated with comprehensive neuropsychological assessments, increasing frailty was statistically significantly associated with worse backward digit span test scores and delayed recognition test performance. No relationship was found between frailty and performance on language tests. These findings suggest specific relationships between increasing frailty and frontal lobe operations that involve working memory and the capacity to encode new information. Both of these neurocognitive operations are associated with MCI and dementia syndromes, such as Alzheimer disease and vascular dementia,24 suggesting that presence of frailty and this profile on neuropsychological test results may be related to the eventual emergence of dementia. Boyle et al14 found that measures of frailty obtained from a sample of more than 700 older persons without cognitive impairment at baseline predicted eventual emergence of MCI. Samper-Ternent et al25 studied a large group of community-dwelling people aged 65 years or older and found that participants with frailty had greater cognitive decline compared with those without frailty; however, neuropsychological functioning was assessed only with the Mini Mental State Evaluation. Gray et al26 studied 2619 community-dwelling people aged 65 years or older for 16 years and found an association between frailty and the eventual risk for dementia. Additional research27 linked baseline frailty to eventual cognitive decline and the emergence of dementia; however, neurocognitive screening tools were used in this research, rather than comprehensive neuropsychological assessment. 
Some research suggests that frailty can be improved with intervention. Gill et al28 found that a home-based treatment intervention program resulted in less functional decline among people with frailty, suggesting considerable cost saving regarding possible admission to institutions and caregiving burden. Langlois et al24 enrolled older adults with frailty into a 12-week exercise program and compared measures of frailty and neuropsychological functioning before and after completion of the program. Older adults with frailty at baseline demonstrated improved physical abilities and performance on neuropsychological tests that measured executive control and working memory.24 A limitation to the current research is modest sample size. Nonetheless, the current research adds to a growing body of research that associates frailty with the presence of specific neuropsychological impairment. 
Frailty is a common medical problem in older adults, and limited research exists regarding its correlation to neurologic impairment. The current study found a correlation between frailty and neuropsychological impairment, which suggests that frailty may be a potential indicator for the emergence of MCI and dementia. Greater awareness of frailty and addressing underlying medical factors that contribute to frailty may prevent or slow the emergence of more serious medical problems. 
Author Contributions
All authors provided substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; all authors drafted the article or revised it critically for important intellectual content; all authors gave final approval of the version of the article to be published; and all authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. 
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