Mild Cognitive Impairment – Neuropsychological and Behavioral Presentation

The following are three cases that illustrate the most common clinical neuropsychological presentations of Mild Cognitive Impairment (MCI) in a neurology clinic.

Case1:

A 68-year-old married man with a high school education and owner-CEO of a large commercial construction company referred for neuropsychological evaluation by his neurologist who is evaluating concerns of a gradual decline in memory. He worries about word finding problems as well as being able to make decisions with increased distractibility. Admits to a history of being anxious, decreased motivation, at times being disorganized and confused. Reports being depressed lately and not feeling confident. Suffers from sleep apnea and does not use the CPAP. Hypertension is present well controlled with medications. MRI of the brain revealed a moderate degree of atrophy and minimal evidence of periventricular white matter changes. Ventricular size is not out of proportion to the degree of atrophy. MMSE score 29/30. The neuropsychological data reflects continue involvement in his day-to-day activities, continues to work but his son now runs the business, able to drive with no reported problems. His cognitive and intellectual abilities are well preserved. Mild short-term memory problems noted but consistent with age. No language, motor or sensory deficits. Prone to making careless errors associated with distractibility. No executive deficits. Screening for depression revealed evidence for a moderate depression. Neuropsychological data is most consistent with depression. Testing provides a baseline marker.

Case 2:

A 71-year-old married man with an MBA worked as a CPA and is now retired. Presents to the neurologist with concerns of a gradual decline of memory over the years worse the last few years. Has resorted to taking notes and does well with this. Also worries about finding words and decreased ability to process information. Wife thinks he is doing well except “not being able to remember very well.” Father had Parkinson’s. Good health. No prescription medication. Continues to be active and socially involved. He is more careful while driving. Sleeps well. Denies depression. Neuropsychological data documents well preserved intelligence and cognition within the context of significant verbal short-term memory problems. Mild word finding problems and decreased processing of information were noted. Mild executive deficits were documented associated with impulsivity and decreased cognitive flexibility. No sensory or motor deficits. Depression screening was normal. MRI showed significant periatrial microvascular white matter changes, visibly not only on FLAIR, but on T1 as well. No evidence of hydrocephalus or of hippocampal atrophy. PET did not show an AD pattern. Neuropsychological data is most consistent with Amnestic Multiple Domain MCI. Suspect a vascular etiology. Testing provides a baseline marker.

Case 3

An 82-year-old divorced woman with two years of college living in an independent living facility presents to the neurologist on 12/2012 with concerns about memory loss first noticed “within the last year.” Worked as church secretary for over 20 years. Hypertension is under good control with medications. Good health otherwise. Sleeps well. She has four grown children who look after her. No history of mental health issues. She gave up driving on her own. No family history of dementia. On Aricept. Daughter concerned about recent memory loss. MRI showed enlarged ventricles. Suspected hydrocephalus but it was ruled out. Neuropsychological data indicated normal intelligence and well preserved cognitive abilities. Processing speed of information was superior. Mild to moderate short-term memory problems documented. Decreased hearing but no other sensory or motor deficits noted. Depression screening was normal. Neuropsychological data is most consistent with Amnestic MCI Single Domain. Testing provides a baseline marker.

Referred again for repeat assessment on 10/2014 because of worsening short-term-memory. She is now 88. Continues to live at the independent living facility. No significant changes in her health. Sleeps well. Neuropsychological interview indicates increased problems relating her recent history. Family reports seeing increased memory problems and concerns about her consistency in taking her medications. They report that she eats food that has gone bad and has gotten sick. She buys things that she does not need and has already bought. She is buying memory supplements. Her children have noted increased irritability and problems managing her life. Neuropsychological data documents in general a mild cognitive decline but a very significant decline in her short-term-memory from a Memory Quotient of 106 to 77. Increased language problems were documented. Increased proneness to making errors was found. Screening for depression was normal. Neuropsychological data documents changes in cognition and memory over a two-year interval with increased problems in managing day-to-day life. The data suggests progression to a degenerative mild-to-moderate dementia when compared with baseline testing.

Learning Objectives

1. Prevalence of MCI.

2. Cognitive subtypes of MCI.

3. Prevalence and incidence of MCI subtypes.

4. The progression of cognitive subtypes of MCI.

5. Predictors of Progression from MCI to Dementia.

6. Risk factors for MCI and Dementia

7. Behavioral-psychological disturbances in MCI

8. Management of MCI.

Prevalence of MCI

Some degree of cognitive decline is normal with age. In MCI, cognitive changes are more substantial than those seen in normal aging, but not severe enough to cause major lifestyle changes. Although there can be progression along the continuum from normal aging to MCI to dementia, this does not always occur. A general estimate of the prevalence of MCI is between 10 and 15 percent of adults over the age of 65.1 Not everyone who has MCI will develop dementia. Some studies indicate that as many as 40 percent of individuals who first meet criteria for MCI return to normal within a year. Mood fluctuations and medication effects can mimic MCI. About 10-15 percent of individuals with MCI will progress to dementia within the first year, and about 50 percent will develop dementia within five years. This is a higher incidence rate than seen for individuals without MCI, but it is worth noting that MCI does not always progress to dementia.2

Cognitive subtypes of MCI

Several subtypes of MCI have been identified. They differ in the type and in the number of cognitive abilities that are impaired. The amnestic MCI describes individuals with significant deficits in memory that either occur in isolation (Amnestic MCI Single Domain) or can be accompanied by deficits in other cognitive domains (Amnestic MCI Multiple Domain). In nonamnestic forms of MCI, individuals exhibit normal performance on memory tasks but show significant deficits on one other cognitive domain such as language, executive functioning, or visualspatial abilities (Nonamnestic MCI Single Domain), or impairment in two or more of such cognitive domains (Nonamnestic MCI Multiple Domain). It has been suggested that these four clinical subtypes may have different underlying etiologies, one of which is an impending dementia or Alzheimer’s disease.3

Prevalence and incidence of MCI subtypes

Findings from population-based studies suggest that more than twice as many people suffer from Nonamnestic Single Domain MCI than Amnestic Single Domain MCI. Multiple Domains, either the nonamnestic or amnestic form, is thought to be the next most frequent form, while Amnestic MCI Single Domain is the least common.4 However, in a clinical setting, the amnestic form of MCI tends to be seen more frequently. A decline in the ability to remember motivates people to seek medical assistance. Other domains of MCI without memory concerns may not be referred or may not be as concerned.2

The progression of cognitive subtypes of MCI

A meta-analysis of 51 clinical and population-based studies showed that people who develop Alzheimer’s disease exhibit cognitive deficits in a range of cognitive functions three or more years prior to the onset of a clinically diagnosable dementia, including global cognitive deficits, and impairment in episodic memory, executive functioning, speed of information processing, language abilities, attention, and visuospatial abilities.6 Research both from clinical and population-based samples show that individuals with amnestic MCI have a high risk of progressing to a full dementia over subsequent years. Three quarters of the people with Amnestic MCI Multiple Domain had reached full dementia syndrome over a three-year period, compared to only 4.7 percent of people with no cognitive impairment and one-third of persons with Amnestic MCI Single Domain. This accounted for a twenty-fold higher risk of developing dementia, especially Alzheimer’s disease, in people with amnestic MCI Multiple Domain compared to people with no cognitive impairment. The dementia risk associated with amnestic MCI Single Domain was lower, but still significant, with a nine-fold risk of dementia compared to cognitively normal elderly. Nonamnestic MCI Single Domain did not have an increased risk of developing dementia or Alzheimer’s disease compared to people with normal cognitive functioning.5

The most typical outcome of MCI depends on the subtype. MCI can be seen as a very early, preclinical phase of different forms of dementia. The different subtypes of MCI may reflect the earliest signs of different forms of dementia. These are the most likely outcomes of different subtypes of MCI6:

• Amnestic MCI Single Domain – Alzheimer’s Disease; Depression.
• Nonamnestic MCI Single Domain – Frontotemporal dementia.
• Amnestic MCI Multiple Domains – Alzheimer’s; Vascular dementia; Depression.
• Nonamnestic MCI Multiple Domains – Lewy Body disease; Vascular dementia.

Predictors of Progression from MCI to Dementia

1. Greater cognitive impairment, and faster rate of cognitive decline.
2. Multiple-domain MCI versus single-domain MCI.
3. More and faster atrophy of medial temporal lobe regions including hippocampus.
4. Apolipoprotein E e-4 allele presence.
5. Positive evidence of amyloid on PET imaging and/or higher ratio of tau protein relative to a particular amyloid protein (AB42) in cerebrospinal fluid.
6. Other cerebrovascular risk factors such as high blood pressure and diabetes.

Risk Factors for MCI and Dementia

Not much is know about MCI risk factors. It is likely that the risk factors for MCI are quite similar to those for dementia. There is no way to determine for sure who will develop MCI. There are both modifiable and non-modifiable risk factors.

Non-Modifiable Risk Factors:

1. Rates of MCI and dementia increase with age.
2. Most studies find no effects of sex on MCI.
3. More people with MCI than older adults without cognitive impairment have the APOE e4allele. However, since MCI is associated with various etiologies, there is likely not a special genetic risk factor for MCI.7
4. TBI has been associated with increased risk of dementia. A few studies also document increased risk for MCI.8

Modifiable Risk Factors:

1. The higher the educational level the lower the risk for MCI or dementia.9
2. Older adults who are cognitively engaged are less likely to develop MCI and dementia.
3. Vascular and metabolic factors.
4. Apathy and depression.

Behavioral- psychological disturbances in MCI

Apathy and depression are the most common neuropsychiatric symptoms in MCI, followed by anxiety, agitation, irritability, nighttime behaviors, and appetite disturbances.10 Symptoms related to psychosis, such as hallucinations and delusions, are not common in MCI. Data from a clinical study on memory clinic outpatients showed that although apathy was associated with an increased risk of progressing to Alzheimer’s disease in patients with MCI, patients with concurrent depression had less of risk of Alzheimer’s disease.10

Management of MCI

To date there are no approved drugs for the management of MCI. A number of clinical trials have demonstrated no convincing effects for delaying conversion to dementia. Various memory intervention programs have been established.11 They combine education, counseling, as well as practice of the cognitive and behavioral strategies taught in the program. The emphasis is in developing procedural memory and habit strategies to develop routines and structured habits. Procedural memory learning remains very stable for longer periods of time in MCI and dementia. Initial research studies found that the program was successful in changing everyday memory behavior in MCI.11 The Mayo Clinic has developed the Healthy Action to Benefit Independence & Thinking (HABIT). Some preliminary data has demonstrated efficacy of the program in increasing quality of life in people with MCI as well as their partner who also participates in the program. n

Francisco I Perez, PhD, ABPP is an Clinical Assistant Professor of Neurology, Baylor College of Medicine

Article reprinted with permission from the Texas Neurological Society: Broca’s Arena, Winter 2015 Newsletter.

1. Gauthier, S., et al., Mild Cognitive Impairment, The Lancet, 2006. 367, 1262-1279.

2. Nilsson, L.G., and Ohta, N., Dementia and Memory, 2014, London and New York: Psychology Press/ Taylor & Francis Group.

3. Perri, R., et al., Characterization of memory profile in subjects with amnestic mild cognitive impairment. Journal of Clinical and Experimental Neuropsychology, 2005. 27, 1033-1055.

4. Petersen, R.C., et al., Mild cognitive impairment: Clinical characterization and outcome, Archives of Neurology, 1999. 56, 303- 308.

5. Petersen, R.C., et al., Mild cognitive impairment: Ten years later. Archives of Neurology, 2009, 66, 1447-1455.

6. Busse, A, et al., Mild cognitive impairment: Prevalence and incidence according to different diagnostic criteria. Results of the Leipzig Longitudinal Study of the Aged (LEILA 75+), British Journal of Psychiatry, 2003, 182, 449-454.

7. Corder, E.H., et al., Gene dose of Apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science, 1993, 261, 921-923.

8. Guskiewicz, K.M., et al., Association between recurrent concussions and late-life cognitive impairment in retired professional football players, Neurosurgery, 57, 719-726.

9. Luck, T., et al., Incidence of mild cognitive impairment: A systematic review. Dementia and Geriatric Cognitive Disorder, 2010, 29, 164-175.

10. Palmer, K., et al., Neuropsychiatric predictors of progression from amnestic- Mild Cognitive Impairment to Alzheimer’s disease. The role of depression and apathy. Journal of Alzheimer’s Disease, 2010, 20(1), 175-183.

11. Anderson, N.D., et al., Living with Mild Cognitive Impairment, 2012, Oxford University Press.