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Brief Report  |   February 2019
Instrumental Activities of Daily Living, Neuropsychiatric Symptoms, and Neuropsychological Impairment in Mild Cognitive Impairment
Author Notes
  • From the Department of Geriatrics and Gerontology and 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 Ms Higgins), and the Department of Psychology at Rowan University in Glassboro, New Jersey (Ms Emrani, Mr Wasserman, and Dr Libon).  
  • Financial Disclosure: 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, Suite 1800, Stratford, NJ 08084-1338. Email: ginsbete@rowan.edu
     
Article Information
Brief Report   |   February 2019
Instrumental Activities of Daily Living, Neuropsychiatric Symptoms, and Neuropsychological Impairment in Mild Cognitive Impairment
The Journal of the American Osteopathic Association, February 2019, Vol. 119, 96-101. doi:https://doi.org/10.7556/jaoa.2019.015
The Journal of the American Osteopathic Association, February 2019, Vol. 119, 96-101. doi:https://doi.org/10.7556/jaoa.2019.015
Web of Science® Times Cited: 1
Abstract

Background: Neuropsychological deficits, neuropsychiatric symptoms, and problems with instrumental activities of daily living are common in participants with mild cognitive impairment (MCI).

Objectives: To assess how subtle to mildly impaired instrumental activities of daily living (IADLs) might be related to neuropsychological abilities (including executive control and episodic memory) and neuropsychiatric symptoms (including apathy and depression) among participants with a diagnosis of MCI.

Methods: Participants were evaluated for MCI and possible dementia at an outpatient memory clinic on the basis of a comprehensive neuropsychological evaluation, a geriatric psychiatry evaluation, a magnetic resonance image of the brain, and serum studies to evaluate for a possible reversible cause of cognitive decline. A series of stepwise regression analyses were conducted whereby IADL ability was the dependent variable and neuropsychological abilities, such as executive control and episodic memory, or neuropsychiatric symptoms, including apathy and depression, were the independent or predictor variables. The presence and severity of neuropsychiatric symptoms was assessed using a modified version of the Neuropsychiatric Inventory (mNPI). Participants were grouped by MCI diagnosis status (amnestic MCI, combined dysexecutive/mixed MCI, and no MCI).

Results: Twenty-six participants were in the amnestic MCI group, 19 in the combined dysexecutive/mixed MCI group, and 36 participants did not meet criteria for MCI (non-MCI group). Groups did not differ in age, education, Mini-Mental State Examination performance, IADL abilities, estimated premorbid general intellectual abilities, or mNPI ratings for apathy and depression. Stepwise regression analyses found a robust relationship between mild IADL impairment and greater apathy (R=0.497, r21,69=0.247, P<.001; β=−0.497, P<.001). Depression did not enter the final model. A weaker—but statistically significant—relationship was found between mild IADL impairment and worse executive control test performance (R=0.271, r21,68=0.073, P<.023; β=0.271, P<.23). Episodic memory did not enter the final model. When both apathy and executive control were assessed as related to IADL impairment, only apathy entered the final model (R=0.497, R21,69=0.247, P<.001; β=−0.497, P<.001).

Conclusion: Mildly impaired IADL functioning can negatively affect quality of life. Moreover, apathy may be amenable to treatment. In a primary geriatric care setting, neuropsychiatric symptoms and neuropsychological abilities should be routinely assessed.

Mild cognitive impairment (MCI) is believed to be a prodrome that eventually leads to the emergence of dementia.1 There is considerable research documenting the neuropsychological parameters associated with MCI.2,3 Patients with MCI also present with a wide number of neuropsychiatric symptoms,4 including depression and apathy.5,6 Moreover, neuropsychiatric problems such as depression and apathy have been shown to be risk factors for the eventual conversion of MCI to dementia.7,8 
Patients with MCI also present with measurable difficulty performing instrumental activities of daily living (IADLs).9,10 Among patients with MCI, impairment involving neuropsychological abilities, such as executive control and episodic memory, as well as neuropsychiatric symptoms, such as depression and apathy, have been linked to eventual conversion to dementia.11-14 Rog et al15 examined performance on tests assessing executive control, episodic memory, neuropsychiatric symptoms, and everyday functions as assessed using the Everyday Cognition scales13 in patients with dementia and MCI. They found a greater association between everyday functioning/IADL impairment and depression and apathy compared with executive control and episodic memory test performance. However, the external validity of this study15 was limited by the use of the Spanish and English Neuropsychological Assessment Scales, which is not widely used. Moreover, this assessment of episodic memory does not include an assessment of delay recognition—a parameter often used to characterize the severity of amnesia in patients with MCI and dementia. 
In the current study, a comprehensive and more traditional neuropsychological protocol was administered to participants suspected of having MCI. The presence of apathy and depression was assessed using a modified version of the Neuropsychiatric Inventory (mNPI).16,17 We sought to examine the relative contribution of both neuropsychological abilities (ie, executive control and episodic memory) vs neuropsychiatric symptoms (ie, apathy and depression) as related to IADL difficulty. 
Methods
Participants
Participants were recruited between February 2016 and September 2017 on the basis of their referral for an evaluation for a putative dementia disorder to the New Jersey Institute for Successful Aging at Rowan University as part of the Memory Assessment Program. 
All participants underwent a comprehensive neuropsychological evaluation and were also examined by a social worker and a board-certified geriatric psychiatrist. Serum blood cell tests included a basic metabolic panel, liver function, rapid plasma reagin, and complete blood cell count, which measured levels of thyroid-stimulating hormone, vitamin B12, and folate, were obtained to evaluate for reversible causes of dementia. Participants also underwent magnetic resonance imaging of the brain using either a 1.5- or 3.0-Tesla Siemens magnetic scanner. T1-weighted spoiled gradient echo (repetition time [TR] 2300 milliseconds, echo time [TE] 1.87 milliseconds), T2-weighted (TR 5500 milliseconds, TE 114 milliseconds), fluid-attenuated inversion recovery (TR 9000 milliseconds, TE 100 milliseconds), and susceptibility weighted (TR 27 milliseconds, TE 20 milliseconds) imaging sequences studies were obtained. 
After all investigations were obtained, a clinical diagnosis for the presence of dementia or MCI1 was determined at an interdisciplinary team conference. Inclusion criteria included history from participants and a knowledgeable family member to suggest insidious onset of neurocognitive decline. Participants were excluded if they had a history of head injury, substance abuse, or major neuropsychiatric disorders (eg, major depressive disorder, epilepsy) or deficiencies in vitamin B12, folate, or thyroid-stimulating hormone. A knowledgeable family member for each participant provided information regarding functional status. 
This study was approved by the Rowan University Institutional Review Board with informed consent obtained consistent with the Declaration of Helsinki. 
Assessment of Cognition and Determination of MCI Subtypes
Gross level of cognitive functioning was assessed using the Mini-Mental State Examination.18 The neuropsychological protocol used to classify MCI subtype assessed executive control, processing speed, naming/lexical access, visuospatial ability, and episodic memory. Standard scores were calculated using age-corrected normative data. Single and multi-domain MCI were classified using criteria suggested by Petersen et al.1 Diagnoses of MCI were single domain amnestic MCI (aMCI), single domain dysexecutive MCI (dysMCI), and mixed or multidomain MCI (mxMCI). 
Assessment of Neuropsychiatric Symptoms
The Neuropsychiatric Inventory measures the presence and severity of 12 neuropsychiatric symptoms, including delusions, hallucinations, depression, apathy, anxiety, irritability, agitation/aggression, disinhibition, elation, aimless motor activity, sleep disorders, and eating disorders. A modified scoring system was applied to the Neuropsychiatric Inventory17 as described by Gallo et al.16 Only ratings for apathy and depression are described in this report. To measure apathy, first, participants’ family members were asked to rate the frequency of the following 8 apathy-related behavior descriptors based on a 4-point scale ranging from 1, “occasionally (less than once/week),” to 4, “very frequently (once or more than once per day)”: 
  • 1. Does the patient seem less spontaneous and less active than usual?
  • 2. Is the patient less likely to initiate a conversation?
  • 3. Is the patient less affectionate or lacking in emotions when compared to his/her usual self?
  • 4. Does the patient contribute less to household chores?
  • 5. Does the patient seem less interested in the activities and plans of others?
  • 6. Has the patient lost interest in friends and family members?
  • 7. Is the patient less enthusiastic about his/her usual interests?
  • 8. Does the patient show any other signs that he/she does not care about doing new things?
If the symptom was not present, it was left blank. The ratings were totaled to obtain a raw score out of a total possible raw score of 32. The sum of these ratings were then divided by the number of descriptors endorsed to achieve the frequency score (eg, 20/6=3.33). Second, family members were asked to provide the overall severity rating for all descriptors endorsed on a 3-point scale (ranging from 1, “mild,” to 3, “marked”). Finally, frequency was multiplied by severity (ie, 1, 2, or 3) to calculate an overall apathy rating (maximum rating of 12). This same procedure was followed to determine frequency, severity, and overall rating of mNPI depression. Using these procedures for all 12 mNPI symptoms, possible scores ranged from 0 to 144. Depression was also assessed using the Geriatric Depression Scales.19 
Assessment of Functional Independence
Instrumental activities of daily living were assessed using the Lawton and Brody20 IADL questionnaire. This questionnaire has a range between 0 and 17, with a higher scoring suggesting intact IADL abilities. Projected premorbid general intellectual functions were assessed using the Wide Range Achievement Test 4 Reading subtest (mean [SD], 100 [15]). Executive abilities were measured using the Trail Making Test–Part B21 and the letter fluency test.22 Episodic memory was assessed using the 9-word California Verbal Learning Test-Short Form23 delay free recall and delay recognition scores. 
Statistical Analysis
One-way analysis of variance was used to assess for between-group differences for demographic variables. Stepwise linear regression was used to examine the relationship between IADL abilities and executive abilities, episodic memory, and mNPI ratings for depression and apathy. Multiple regression analyses were conducted whereby IADL ability was the dependent variable and neuropsychological or neuropsychiatric variables were the independent variables. Statistical significance was defined as P≤.05. 
Results
A total of 77 participants were available for data analysis. On the basis of the criteria described above, 26 participants received a diagnosis of aMCI, 4 received a diagnosis of dysMCI, and 15 received a diagnosis of mxMCI. Because of the small number of participants with dysMCI, a combined dysexecutive/mixed (dys/mx) MCI subgroup (n=19) was constructed. An additional 36 participants who presented for clinical evaluation did not meet criteria for MCI (non-MCI group). The 3 groups of MCI participants did not differ based on age, education, or IADL ability. There were also no between-group differences in total mNPI score or mNPI ratings of depression and apathy (Table) or in gross level of cognitive functioning, depression (as assessed with the Geriatric Depression Scales), or projected premorbid general intellectual functions. 
Table.
Demographic Information, Neuropsychiatric Symptoms, and Neuropsychological Performance
Group, Mean (SD)
Measure non-MCI aMCI dys/mxMCI
Demographics
 Age, y 76.91 (6.41) 74.81 (7.02) 77.84 (5.31)
 Education, y 14.44 (3.03) 14.81 (2.64) 13.52 (2.87)
Clinical Findings
 MMSE (range, 0-30) 27.72 (1.68) 26.59 (2.34) 26.63 (1.73)
 GDS (range, 0-30) 3.33 (2.61) 3.09 (2.44) 4.11 (3.02)
 IADL scale (range, 0-17) 14.93 (2.35) 13.95 (3.05) 14.23 (2.70)
Neuropsychiatric Symptoms
 mNPI, apathy (range, 0-12) 1.01 (1.43) 1.83 (2.96) 0.95 (1.49)
 mNPI, depression (range, 0-12) 1.29 (1.58) 1.17 (1.84) 0.80 (1.49)
Neuropsychological Tests, z score
 WRAT4 Readinga 114.94 (18.38) 116.72 (13.48) 109.89 (16.23)
 Trail Making Test–Part Bb −0.16 (0.81) −0.34 (0.91) −0.62 (0.87)
 Letter fluencyb −0.12 (0.86) −0.65 (0.96) −1.30 (0.86)
 CVLT-SF delay free recallb −0.33 (1.01) −1.81 (0.58) −0.88 (1.14)
 CVLT-SF delay recognitionb 0.22 (0.83) −1.43 (0.76) −0.36 (0.95)
  a Mean (SD), 100 (15). b Mean (SD), 0 (1).
  Abbreviations: aMCI, amnestic mild cognitive impairment; CVLT-SF, California Verbal Learning Test-Short Form; dys/mxMCI, dysexecutive/mixed mild cognitive impairment; GDS, Geriatric Depression Scale; IADL, Instrumental Activities of Daily Living; MMSE, Mini Mental State Examination; mNPI, modified Neuropsychiatric Inventory; non-MCI, mild cognitive impairment not present; WRAT-IV Reading, Wide Range Achievement Test 4 Reading subtest.
Table.
Demographic Information, Neuropsychiatric Symptoms, and Neuropsychological Performance
Group, Mean (SD)
Measure non-MCI aMCI dys/mxMCI
Demographics
 Age, y 76.91 (6.41) 74.81 (7.02) 77.84 (5.31)
 Education, y 14.44 (3.03) 14.81 (2.64) 13.52 (2.87)
Clinical Findings
 MMSE (range, 0-30) 27.72 (1.68) 26.59 (2.34) 26.63 (1.73)
 GDS (range, 0-30) 3.33 (2.61) 3.09 (2.44) 4.11 (3.02)
 IADL scale (range, 0-17) 14.93 (2.35) 13.95 (3.05) 14.23 (2.70)
Neuropsychiatric Symptoms
 mNPI, apathy (range, 0-12) 1.01 (1.43) 1.83 (2.96) 0.95 (1.49)
 mNPI, depression (range, 0-12) 1.29 (1.58) 1.17 (1.84) 0.80 (1.49)
Neuropsychological Tests, z score
 WRAT4 Readinga 114.94 (18.38) 116.72 (13.48) 109.89 (16.23)
 Trail Making Test–Part Bb −0.16 (0.81) −0.34 (0.91) −0.62 (0.87)
 Letter fluencyb −0.12 (0.86) −0.65 (0.96) −1.30 (0.86)
 CVLT-SF delay free recallb −0.33 (1.01) −1.81 (0.58) −0.88 (1.14)
 CVLT-SF delay recognitionb 0.22 (0.83) −1.43 (0.76) −0.36 (0.95)
  a Mean (SD), 100 (15). b Mean (SD), 0 (1).
  Abbreviations: aMCI, amnestic mild cognitive impairment; CVLT-SF, California Verbal Learning Test-Short Form; dys/mxMCI, dysexecutive/mixed mild cognitive impairment; GDS, Geriatric Depression Scale; IADL, Instrumental Activities of Daily Living; MMSE, Mini Mental State Examination; mNPI, modified Neuropsychiatric Inventory; non-MCI, mild cognitive impairment not present; WRAT-IV Reading, Wide Range Achievement Test 4 Reading subtest.
×
Stepwise linear and multiple regression analyses examining the relationship between IADL and neuropsychiatric symptoms was significant, with only apathy entering the final model (R=0.497, r21,69=0.247, P<.001; β=−0.497, P<.001) such that a lower (ie, more impaired) IADL ability was associated with greater apathy. Depression did not enter the final model. Stepwise linear and multiple regression analyses examining IADL abilities and executive test performance were also significant (R=0.271, r21,68=0.073, P<.023; β=0.271, P<.023), with lower IADL ability associated with worse Trail Making Test–Part B test performance. Letter fluency did not enter the final model. A similar regression analysis demonstrated no association between IADL abilities and episodic memory. A final multiple regression analysis of caregiver mNPI rating of apathy and Trail Making Test–Part B performance as related to IADL functioning was significant (R=0.497, R21,69= 0.247, P<.001, β=−0.497, P<.001). Only apathy entered the final model such that lower IADL ability was associated with higher caregiving ratings for apathy. These analyses were also conducted for only participants with MCI, and the results were unchanged. 
Discussion
The current research sought to examine the relationship between neuropsychological functions as assessed with tests of executive control, episodic memory, and neuropsychiatric symptoms as rated by caregivers for apathy and depression in patients with MCI. We found a strong and robust relationship between diminished IADL abilities in patients with MCI and apathy but not depression. We also found a weaker relationship between impaired IADL abilities and poorer performance on the Trail Making Test–Part B, which assesses the capacity of participants to maintain a complex mental set and working memory. However, when apathy and Trail Making Test–Part B test performance were evaluated together in participants with MCI, only apathy was associated with diminished IADL functioning. Rog et al15 obtained similar results, showing that greater IADL disability was associated with greater depression and apathy when compared with performance on executive and memory tests. These findings suggest that impaired IADL ability in participants with MCI is likely multifactorial,15 involving both neuropsychiatric and neuropsychological problems. Also, although our study used different but complementary assessment procedures, both studies replicate and extend the findings of Rog et al.15 
Apathy is defined as a reduction of self-generated voluntary and purposeful goal-directed behavior.24 According to Massimo et al,25 apathy may comprise 3 components, including initiation (the ability to self-generate or activate actions), planning (the ability to elaborate plans of action to attain a goal), and motivation (the ability to prospectively associate positive or negative consequences in performing actions). Derailed capacity to execute any of these 3 components could result in apathy. Moreover, intact executive abilities are likely necessary to effectively operate all 3 of these apathy subcomponents,25 which are associated with differing underlying neuroanatomical networks. Although the mNPI provides a gross, overall measure of apathy, it was not designed to examine or disambiguate individual components that may give rise to apathy. An interesting question for future research is determining whether IADL impairment that develops in patients with MCI is related to individual subcomponents of apathy as characterized by Massimo et al.25 
Mild cognitive impairment is primarily defined and characterized in terms of neurocognitive disability. Our findings imply that there is a need to characterize MCI more broadly considering neurocognition, the presence of neuropsychiatric problems, and possible IADL impairment. Up to 16% of patients with MCI revert to normal neuropsychological functioning.26 It would be interesting to know whether treatment or resolution of neuropsychiatric symptoms is at least partially responsible for improved neuropsychological abilities. This topic must be explored in future research. 
Conclusion
To the extent that apathy can be successfully managed, both neuropsychological and IADL abilities might also be improved. Our findings indicate the need for geriatric physicians to routinely assess patients with MCI for neuropsychiatric problems, including the presence of apathy, and to make appropriate referral for treatment and further evaluation when apathy and other neuropsychiatric problems are present. In participants with MCI, we found that there is a greater effect of neuropsychiatric problems on IADL than neuropsychological functioning. 
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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Table.
Demographic Information, Neuropsychiatric Symptoms, and Neuropsychological Performance
Group, Mean (SD)
Measure non-MCI aMCI dys/mxMCI
Demographics
 Age, y 76.91 (6.41) 74.81 (7.02) 77.84 (5.31)
 Education, y 14.44 (3.03) 14.81 (2.64) 13.52 (2.87)
Clinical Findings
 MMSE (range, 0-30) 27.72 (1.68) 26.59 (2.34) 26.63 (1.73)
 GDS (range, 0-30) 3.33 (2.61) 3.09 (2.44) 4.11 (3.02)
 IADL scale (range, 0-17) 14.93 (2.35) 13.95 (3.05) 14.23 (2.70)
Neuropsychiatric Symptoms
 mNPI, apathy (range, 0-12) 1.01 (1.43) 1.83 (2.96) 0.95 (1.49)
 mNPI, depression (range, 0-12) 1.29 (1.58) 1.17 (1.84) 0.80 (1.49)
Neuropsychological Tests, z score
 WRAT4 Readinga 114.94 (18.38) 116.72 (13.48) 109.89 (16.23)
 Trail Making Test–Part Bb −0.16 (0.81) −0.34 (0.91) −0.62 (0.87)
 Letter fluencyb −0.12 (0.86) −0.65 (0.96) −1.30 (0.86)
 CVLT-SF delay free recallb −0.33 (1.01) −1.81 (0.58) −0.88 (1.14)
 CVLT-SF delay recognitionb 0.22 (0.83) −1.43 (0.76) −0.36 (0.95)
  a Mean (SD), 100 (15). b Mean (SD), 0 (1).
  Abbreviations: aMCI, amnestic mild cognitive impairment; CVLT-SF, California Verbal Learning Test-Short Form; dys/mxMCI, dysexecutive/mixed mild cognitive impairment; GDS, Geriatric Depression Scale; IADL, Instrumental Activities of Daily Living; MMSE, Mini Mental State Examination; mNPI, modified Neuropsychiatric Inventory; non-MCI, mild cognitive impairment not present; WRAT-IV Reading, Wide Range Achievement Test 4 Reading subtest.
Table.
Demographic Information, Neuropsychiatric Symptoms, and Neuropsychological Performance
Group, Mean (SD)
Measure non-MCI aMCI dys/mxMCI
Demographics
 Age, y 76.91 (6.41) 74.81 (7.02) 77.84 (5.31)
 Education, y 14.44 (3.03) 14.81 (2.64) 13.52 (2.87)
Clinical Findings
 MMSE (range, 0-30) 27.72 (1.68) 26.59 (2.34) 26.63 (1.73)
 GDS (range, 0-30) 3.33 (2.61) 3.09 (2.44) 4.11 (3.02)
 IADL scale (range, 0-17) 14.93 (2.35) 13.95 (3.05) 14.23 (2.70)
Neuropsychiatric Symptoms
 mNPI, apathy (range, 0-12) 1.01 (1.43) 1.83 (2.96) 0.95 (1.49)
 mNPI, depression (range, 0-12) 1.29 (1.58) 1.17 (1.84) 0.80 (1.49)
Neuropsychological Tests, z score
 WRAT4 Readinga 114.94 (18.38) 116.72 (13.48) 109.89 (16.23)
 Trail Making Test–Part Bb −0.16 (0.81) −0.34 (0.91) −0.62 (0.87)
 Letter fluencyb −0.12 (0.86) −0.65 (0.96) −1.30 (0.86)
 CVLT-SF delay free recallb −0.33 (1.01) −1.81 (0.58) −0.88 (1.14)
 CVLT-SF delay recognitionb 0.22 (0.83) −1.43 (0.76) −0.36 (0.95)
  a Mean (SD), 100 (15). b Mean (SD), 0 (1).
  Abbreviations: aMCI, amnestic mild cognitive impairment; CVLT-SF, California Verbal Learning Test-Short Form; dys/mxMCI, dysexecutive/mixed mild cognitive impairment; GDS, Geriatric Depression Scale; IADL, Instrumental Activities of Daily Living; MMSE, Mini Mental State Examination; mNPI, modified Neuropsychiatric Inventory; non-MCI, mild cognitive impairment not present; WRAT-IV Reading, Wide Range Achievement Test 4 Reading subtest.
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