Phenomenology of MCI

The phenomenology of MCI has been examined using both quantitative and qualitative research methods. Studies using a quantitative approach, such as administering questionnaires to people with MCI and healthy older adults, have found reduced quality-of-life in individuals with MCI,Reference Bárrios, Narciso, Guerreiro, Maroco, Logsdon and de Mendonça ^{21 ,} Reference Teng, Tassniyom and Lu ²² particularly when they are aware of their diagnosis.Reference Stites, Karlawish, Harkins, Rubright and Wolk ²³ Symptoms of depression, anxiety, hostility, and low morale have also been reported to be elevated in people with MCI compared to healthy older adults.Reference Clément, Belleville, Bélanger and Chassé ²⁴ Indeed, people with MCI experience depressive symptoms at approximately double the rate of healthy seniors,Reference Ravaglia, Forti and Lucicesare ^{25 ,} Reference Shahnawaz, Reppermund and Brodaty ²⁶ with one of these studies finding that symptoms of depression, including those that met the cut-off for clinical significance, were elevated in individuals with amnestic, but not non-amnestic, MCI.Reference Shahnawaz, Reppermund and Brodaty ²⁶ The authors argued that depression can result when memory difficulties interfere with the ability to perform instrumental activities of daily living, but it should be noted that such activities also rely on executive functions.Reference Overdorp, Kessels, Claassen and Oosterman ²⁷

A handful of qualitative studies have shared the lived experience of people with mild cognitive impairment. Roberts and ClareReference Roberts and Clare ²⁸ used interpretative phenomenological analysis of interview data with 25 people who had been diagnosed with MCI, a method which interprets the meaning of the statements shared by participants. Their analysis identified 4 themes. The first theme reflected participants’ appraisals of their cognition in the context of their perceived social network: individuals living alone identified retention of independence as being of high importance, in fear it might be taken away, while those who lived with others leaned on their partners to maintain their independence. The second theme reflected a normalization of participants’ own memory problems, viewing them as a normal consequence of aging, with comments such as “All my friends forget things too.” The third theme described participants’ unwillingness to consider negative impact or outcomes as a result of their diagnoses. Participants often used humor to deflect the seriousness of their condition. The final theme reflected participants’ lack of sophisticated knowledge about what MCI is and their concerns for the future. While these last two themes may seem to contradict each other, the frequent vacillation between memory concerns and minimization of the significance of their diagnosis is commonly observed in clinical practice, often times even in a single statement, eg, “I worry all the time I might become demented, but then again, all my friends forget things!”

Berg et al Reference Berg, Wallin, Nordlund and Johansson ²⁹ interviewed 17 individuals who maintained a diagnosis of MCI across 4 assessments over a 7-year period. The majority of them expressed wanting to spare their children of the experiences they had caring for their mothers with dementia. Another common theme, like the results of Roberts and Clare,Reference Roberts and Clare ²⁸ was attribution of the experienced memory difficulties to normal aging, a minimization which may also be a form of avoidant coping. Most participants expressed concerns for the future and the impending loss of capabilities and the impact that this will have on their participation in activities they find meaningful. Finally, participants reported avoidant coping behaviors, reducing stress by avoiding situations they thought they could not handle.

Avoidant coping was also a key observation of the qualitative study of 14 individuals with amnestic MCI reported by Parikh et al.Reference Parikh, Troyer, Maione and Murphy ³⁰ These individuals reported withdrawing from the social activities they previously enjoyed to avoid embarrassment and frustration when their memory fails them in these settings. Social exclusion was also reported, such as being interrupted when they hesitate in conversations, and feeling that their friends no longer share information with them in the way they had previously.

In summary, this literature paints a picture of reduced quality of life, elevated symptoms of depression, and avoidant coping strategies such as minimizing the significance of one’s diagnosis and withdrawing from leisure activities as key features of the phenomenology of MCI. Treating depression and not only encouraging, but facilitating, social engagement are important elements in the treatment of MCI, as discussed in the final section of this article, particularly given the identified role of depression and reduced social engagement as risk factors for dementiaReference Marioni, Proust-Lima and Amieva ^{31 ,} Reference Norton, Matthews, Barnes, Yaffe and Brayne ³² and the influence of depression in the progression from MCI to dementia.Reference Van der Mussele and Fransen ³³

Neurobiology of MCI

All of the neuropathologies identified in MCI cohorts can also be found in seniors with intact cognition and in seniors with dementia, and typically fall in the intermediate stage in terms of severity.Reference Stephan, Hunter and Harris ³⁴ These include atrophy of medial temporal lobe regions, particularly the hippocampus and entorhinal regions, and posterior cingulate cortex,Reference Fennema-Notestine, McEvoy, Hagler, Jacobson and Dale ³⁵ hypometabolism in temporoparietal and posterior cingulate cortices, as assessed by fluorodeoxyglucose positron emission tomography (FDG-PET);Reference Kim, Seo and Yoon ³⁶ and hypoperfusion of parietal cortices and the hippocampus as measured by single-photon emission computed tomography (SPECT).Reference Habert, Horn and Sarazin ³⁷

The other primary neurobiological markers of MCI pertain to the neuropathology of AD–amyloid plaques and neurofibrillary tangles. Evidence of amyloid accumulation in MCI (and AD) can be detected with positron emission tomography using the (11)C-labelled Pittsburgh Compound-B ((11)C-PIB) ligand. The great variability in how PIB scans are performed and interpreted has raised calls for greater standardization of this high cost procedure.Reference Zhang, Smailagic, Noel-Storr, Takwoingi, McShane and Feng ³⁸ Amyloid beta (Aβ₄₂) can be detected in the cerebrospinal fluid (CSF) at much lower cost, with lower CSF Aβ₄₂ concentrations indicating higher levels of brain Aβ₄₂ (ie, poorer clearance), whereas elevated CSF concentrations of total tau and phosphorylated tau indicate neuronal injury and predict progression from MCI to AD-related dementia. Both CSF Aβ₄₂ and tau, as well as PET PIB, have better sensitivity than specificity,Reference Ritchie, Smailagic, Noel-Storr, Ukoumunno, Ladds and Martin ^{39 ,} Reference Ritchie, Smailagic and Noel-Storr ⁴⁰ suggesting that they are more useful in ruling out preclinical AD than in confirming it.

The epsilon 4 allele of the apolipoprotein gene (APOE-e4) confers a risk for MCI, as it does for AD.Reference Qian, Wolters and Beiser ⁴¹ Differences in gene expression in cortical brain regions have been reported in MCI that are unique compared to healthy cohorts and those with AD.Reference Berchtold, Sabbagh, Beach, Kim, Cribbs and Cotman ⁴² These authors report an upregulation of genes associated with anabolic and biosynthetic pathways and mitochondrial energy generation. Upregulation of genes associated with synaptic transmission and plasticity was also identified in entorhinal cortex and hippocampus, but this was associated with poorer cognitive functioning as assessed with the Mini-Mental State Examination (MMSE).Reference Folstein, Folstein and McHugh ⁴³ This finding is reminiscent of previous reports of a “paradoxical” hyperactivation of the hippocampus during encoding in MCI, with greater hyperactivation associated with greater atrophy and cortical thinning in medial temporal lobe regions.Reference Dickerson, Salat and Greve ^{44 ,} Reference Putcha, Brickhouse and O’Keefe ⁴⁵ One interpretation of this apparent paradox is that it is the brain’s last ditch attempt to maintain functioning in the face of mounting neuropathology.

The elevated rates of depression in MCI deserve mentioning in the context of the neurobiology of MCI. There is much debate about the causal relationship between depression and MCI. As spelled out by Shahnawaz et al,Reference Shahnawaz, Reppermund and Brodaty ²⁶ 4 mechanisms of this relationship have been proposed: (1) the downstream consequences of depression (eg, elevated cortisol and its effects on the brain) may cause cognitive decline;Reference Jorm ⁴⁶ (2) depression may be an early outcome of MCI as individuals experience cognitive decline;Reference Slavin, Brodaty and Kochan ⁴⁷ (3) an independent, third variable commonly comorbid with both conditions, such as vascular disease, may be causing both depression and cognitive decline;Reference Ownby, Crocco, Acevedo, John and Loewenstein ⁴⁸ and (4) medications for depression may exacerbate cognitive decline due to their anticholinergic effects.Reference Kuchibhatla, Fillenbaum, Hybels and Blazer ⁴⁹

Emerging approaches in neuroimaging may prove useful for early detection of MCI. For example, altered synchronization of brain signals has been reported using magnetoencephalography (MEG)Reference Buldú, Bajo and Maestú ⁵⁰ and functional magnetic resonance imaging (fMRI).Reference Seo, Lee and Lee ⁵¹ Likewise, electroencephalography (EEG) and MEG studies have shown increased power in low frequencies (delta and theta bands) and decreased power in higher frequencies (alpha and beta bands) in people with MCI compared to controls,Reference McBride, Zhao and Munro ⁵² suggesting a shift away from firing patterns required for complex cognitive processes, such as working memory and avoiding distraction, toward more basic processes such as orienting attention. Analyses of the complexity of EEG and MEG time-series data, such as entropy, typically show reduced signal complexity compared to healthy older adults,Reference McBride, Zhao and Munro ^{52 ,} Reference Bruña, Poza, Gómez, García, Fernández and Hornero ⁵³ suggesting that people with MCI have less complex (ie, more regular) neural dynamics, thus limiting the repertoire of brain states and restricting transitions between states.Reference McIntosh, Kovacevic and Itier ⁵⁴ Moreover, the synchrony of resting-state EEG oscillatory neural activity may be reduced in MCI,Reference Dauwels, Srinivasan and Ramasubba Reddy ⁵⁵ restricting short-range and long-range communication.

A final neurobiological biomarker that is also not part of standard diagnostic practices, but has promise for the future, is the structural and functional integrity of perirhinal cortex. Given that Alzheimer’s pathology begins in the transentorhinal cortex,Reference Braak and Braak ⁵⁶ which corresponds to the medial perirhinal cortex,Reference Taylor and Probst ⁵⁷ it is not surprising that a hallmark feature of amnestic MCI is atrophy and thinning of the rhinal cortices (see Zhou et al Reference Zhou, Zhang, Zhao, Qian and Dong ⁵⁸ for a review), combined with hippocampal atrophy that exceeds that seen in healthy aging (see Leal and YassaReference Leal and Yassa ⁵⁹ for a review). The volume of the anterolateral entorhinal cortex has recently been reported to correlate with performance on the Montreal Cognitive Assessment (MoCA),Reference Nasreddine, Phillips and Bédirian ⁶⁰ a cognitive screening tool that is sensitive to MCI, in a group of healthy older adults, some of whom had failed the MoCA.Reference Olsen, Yeung and Noly-Gandon ⁶¹ Perirhinal neurofibrillary tangle deposition in people with MCI has also been recently reported,Reference Wolk, Das, Mueller, Weiner and Yushkevich ⁶² and in early AD, greater perirhinal atrophy is associated with greater tau deposition, whereas greater hippocampal atrophy is associated with greater amyloid deposition.Reference Sone, Imabayashi and Maikusa ⁶³ Thus, the deployment of high-resolution structural magnetic resonance imaging to assess the volume and cortical thickness of perirhinal cortices, and the combination of fMRI with clever tasks that drive perirhinal and lateral entorhinal processes, as discussed in the next section of this article, may be fruitful avenues for early detection of MCI.

Assessment of MCI

The current clinical and research criteria for diagnosis of MCI were enumerated at the outset of this article. This section will comment on how those criteria are assessed. In clinical practice, and as per the research criteria for the assessment of MCI, neuroimaging is often performed. This can include SPECT and/or FDG-PET to verify hypoperfusion and glucose hypometabolism of temporoparietal cortices, respectively; structural MRI to identify medial temporal lobe atrophy; and CSF assays to verify elevated levels of tau and phosphorylated tau, all indicative of neuronal injury. Likewise, reduced CSF levels of Aβ₄₂ (indicative of elevated brain levels of Aβ₄₂) or of Aβ₄₂ deposition in the brain using PET imaging are increasingly common tests at least in better resourced communities to confirm MCI diagnosis. A recent international working group published guidelines for CSF biomarker in the diagnosis of MCI concluded that CSF biomarkers hold significant utility in predicting conversion to AD 3 years later, but the evidence was too limited to recommend any one CSF biomarker over another.Reference Herukka, Hviid Simonsen and Andreasen ⁶⁴ Finally, confirmation that a client carries 1 or 2 ε4 alleles in the APOE gene increases confidence in the diagnosis of MCI due to AD.

Researchers are constantly aiming to identify lower cost, less invasive biomarkers of AD neuropathology in the preclinical phases of the disease. One group recently reported the utility of a blood plasma–based composite biomarker of Aβ deposition that fared very well against PIB-PET imaging and CSF Aβ.Reference Nakamura, Kaneko and Villemangne ⁶⁵ Thus, the notion that individuals can receive an early diagnosis in their family physician’s office, and then be directed toward treatments that delay progression to dementia, is foreseeable.

In addressing the diagnostic criteria of cognitive impairment in clinical practice, it is not uncommon for physicians to rely solely on a cognitive screening measure such as the MMSE or the MoCA. The MMSE, however, lacks in sensitivity to detect MCI,Reference Nasreddine, Phillips and Bédirian ⁶⁰ and the MoCA is insufficient to determine the specific cognitive domains affected in order to determine MCI subtype (although see Julayanont et al Reference Julayanont, Brousseau, Chertkow, Phillips and Nasreddine ⁶⁶ for an approach that hopefully will be validated against a more extensive assessment). There are 3 versions of the MoCA, permitting re-assessment without undue influence of practice effects; however, the first version of the test was published by media outlets in January 2018, following the news that President Trump had passed it, and so clinicians are now recommended to avoid using this version in case their clients have become familiar with the test items.

A more comprehensive approach to cognitive assessment involves a neuropsychological assessment. Neuropsychologists typically administer a 90-minute to 3-hour assessment of cognitive functioning and factors that could influence performance (eg, mood, self-report of learning disabilities, other major medical conditions, sensory and language fluency limitations). The neuropsychological assessment typically includes measures of memory, executive functioning, attention, language, and visuospatial skills. In the diagnosis of MCI (and other conditions for that matter), it is important to find evidence of impairments across multiple tests within a cognitive domain, such as on multiple tests of episodic memory. This is because a surprisingly high percentage of healthy seniors will score below cut-off on at least 1 memory measure in a battery (eg, 38% scoring < 5th percentile in Brooks et al Reference Brooks, Iverson, Holdnack and Feldman ⁶⁷ and > 60% scoring < 10th percentile in Mistridis et al Reference Mistridis, Egli and Iverson ⁶⁸ ), rendering the potential for misdiagnosis of MCI high if made on the basis of 1 failed test. Those examples also highlight the variability in the literature and in clinical practice in how a cognitive “impairment” is operationalized, with some using a cut-off of 1.5 standard deviations (SD) below the age- (and education-, where available) corrected normative data (<7th percentile), and others using a less stringent –1.0 SD cut-off (<16th percentile). This inconsistency in diagnostic practice contributes to the variability in not only prevalence and incidence rates of MCI, but also in its prognostic patterns.

Failing to take a clients’ medical and psychosocial history into account in differential diagnosis can likewise lead to misclassification of MCI; for example, if a client reports that his memory difficulties emerged following open-heart surgery, but have not continued to decline, memory impairment secondary to hippocampal damage due to anoxia could be mistaken for preclinical dementia. Issues such as these likely contribute to the sometimes high rates of “reversion to normal” when people previously diagnosed with MCI are tested later and score within normal ranges (for a meta-analysis, see Malek-AhmadiReference Malek-Ahmadi ⁶⁹ ).

Another contentious aspect about the assessment of MCI has been the criterion regarding subjective concern. The unreliable nature of memory concerns in MCI that was mentioned in a previous section of this article has been validated by studies reporting poor associations between the degree of subjective memory concerns and actual memory performance in MCIReference Lenehan, Klekociuk and Summers ⁷⁰ (see Roberts et al Reference Roberts, Clare and Woods ⁷¹ for an earlier review), most typically reflecting an underestimation of the magnitude of actual impairment.Reference Edmonds, Delano-Woods, Galasko, Salmon and Bondi ⁷² This has led many investigators to question the reliability of the patients’ concerns about their memory (versus the concerns of a family member and/or healthcare professional) as a core clinical criterion for MCI. Yet, it should be noted that the impetus for including in the diagnostic criteria a concern that one’s memory (or other cognitive domain) is becoming worse was to distinguish a probable neurodegenerative process from a non-degenerative process.

A final point about the cognitive assessment of MCI relates to the assessment tools used in neuropsychology, which have a rich history, with most developed or at least rooted in early efforts to understand brain–behavior relationships. New versions of tests are frequently released, but the tests remain essentially the same. One implication of the relative rigidity of neuropsychological practices is that assessment tends not to capitalize on recent advances in our understanding of the neurobiology of conditions, including MCI. Given that the earliest neuropathological changes in MCI occur in the perirhinal cortex, as mentioned in the previous section of this article, cognitive tests that tap into perirhinal functioning may prove to be particularly sensitive to MCI. The perirhinal cortex and lateral entorhinal cortex have been discovered to mediate complex object discrimination,Reference Barense, Gaffan and Graham ^{73 –} Reference Lee, Bandelow, Schwarzbauer, Henson and Graham ⁷⁵ whereas spatial information is processed by an alternate medial temporal lobe route involving the parahippocampal gyrus and medial entorhinal cortex.Reference Ranganath and Ritchey ⁷⁶ Indeed, compared to their healthy counterparts, people with aMCI report problems with “object memory,” forgetting what things are called, what they watched on television, to do things that are right in front of them, but share similar complaints with healthy seniors about “spatial memory,” such as where they put things or recognizing places.Reference Ahmed, Mitchell, Arnold, Dawson, Nestor and Hodges ^{77 ,} Reference Farias, Mungas, Reed, Harvey, Cahn-Weiner and DeCarli ⁷⁸ The perirhinal cortex has also been implicated in the mnemonic process of familiarity—the gut sense that you have experienced something before but you fail to remember the original context of the event.Reference Bowles, Crupi and Pigott ^{79 –} Reference Martin, Bowles, Mirsattari and Köhler ⁸¹

This literature would suggest that tests of complex object discrimination (and memory for objects when they have to be distinguished from highly similar lures) and tests of familiarity may be particularly sensitive to MCI. Indeed, MoCA performance was more strongly associated with the ability to select a studied item over a highly similar lure item for objects than scenes in the study by Fidalgo et al,Reference Fidalgo, Changoor, Page-Gould, Lee and Barense ⁸² and people with MCI have greater difficulty identifying objects when they are presented in an overlapping line-drawn display.Reference Alegret, Boada-Rovira and Vinyes-Junqué ⁸³ The literature on whether familiarity is spared or impaired is split, with approximately half of the studies finding spared familiarity in MCI (eg, Reference Anderson, Ebert, Jennings, Grady, Cabeza and Graham ^{84 ,} Reference Hudon, Belleville and Gauthier ⁸⁵ ) and the other half finding familiarity deficits in MCI (eg, Reference Ally, Gold and Budson ^{86 ,} Reference Wolk, Mancuso, Kliot, Arnold and Dickerson ⁸⁷ ). This author believes this confusion can be attributed to how familiarity is typically assessed experimentally, pitting it against recollection (the ability to recall a prior event and its context), and advocates for more novel approaches to assess familiarity free from the influence of recollection. Indeed, one study in this vein had older adults who were either carriers or noncarriers of APOE ε4 study faces against a red or blue background.Reference Schoemaker, Poirier, Escobar, Gauthier and Pruessner ⁸⁸ Later, they performed a yes/no recognition task of the studied faces intermixed with new faces, and then for faces deemed “old” (studied), indicated if it was studied with a red or blue background. The two groups did not differ in the ability to recognize a studied face and remember its context (recollection), but ε4 carriers were less likely to recognize a studied face but not remember its studied context (familiarity).

Despite all of the neurobiological reasons to think that complex object discrimination or familiarity may be exquisitely sensitive to MCI, standardized tests of these abilities have not been developed. It is high time that the assessment of MCI (and other neurological disorders) catches up with state of neuroscience research findings.

Treatment of MCI

Given that MCI, particularly in its amnestic form, is often a precursor to AD, it is not surprising that most (70%) physicians report prescribing cholinesterase inhibitors “off-label” at least sometimes in this cohort, and 39% reported prescribing memantine.Reference Roberts, Karlawish, Uhlmann, Petersen and Green ⁸⁹ These prescribing practices occur despite the continued lack of high-quality evidence for their efficacy in MCI,Reference Petersen, Lopez and Armstrong ¹⁶ perhaps because physicians suspect that their patients might have progressed to the early stages of AD.Reference Roberts, Karlawish, Uhlmann, Petersen and Green ⁸⁹ Likewise, there is insufficient evidence to support treatment of MCI with alternate agents such as the nicotine patch or vitamin E.Reference Petersen, Lopez and Armstrong ¹⁶ Physicians are recommended to wean their patients off other medications that may impair cognition, and to treat other modifiable risk factors that may be contributing to cognitive impairment, including mood disorders.Reference Petersen, Lopez and Armstrong ¹⁶

Given that there are no disease-modifying agents for MCI, and that the symptomatic treatments for AD lack efficacy in MCI, what can be done for people in this precarious state? The approaches described in the remainder of this section are not cures, and no one holds the belief that these measures will have direct effects on the neuropathological changes occurring in MCI, but there is still reason to think that they may delay progression to dementia. This thought rests on the fact that to progress to dementia one has to have cognitive deficits that are severe enough to interfere significantly with everyday functioning. Thus, if we can raise an individual’s level of cognitive functioning, that person will have to experience a greater degree of cognitive decline before progressing to dementia, which will essentially buy him or her more time in relatively good cognitive health. This idea is a corollary of the notion of reserveReference Stern ⁹⁰ that has been offered to explain the discrepancy between the degree of neuropathology and one’s level of cognitive functioning. Research has identified several early-life and mid-life factors, such as educational and occupational attainment, that increase reserve and permit individuals to tolerate higher levels of neuropathology yet maintain their cognitive functioning.Reference Stern ⁹⁰ Reserve can be neural, for example by fostering richer neural connections, or cognitive, allowing individuals to approach tasks in new ways.Reference Stern ⁹⁰ The approaches described below are efforts to enhance neural and/or cognitive reserve.

Physical exercise interventions have shown small but significant neural and cognitive benefits for cognition in people with MCI (for a meta-analysis, see Ströhle et al Reference Ströhle, Schmidt and Schultz ⁹¹ ). For example, Baker et al Reference Baker, Frank and Foster-Schubert ⁹² randomized 33 people with amnestic MCI to either aerobic training or a stretching control group 4 times a week over 6 months. In addition to the expected effects on cardiorespiratory fitness, aerobic training was associated with improved attention and executive functioning. However, the association between improvements in cardiorespiratory functioning (VO₂ peak) and these cognitive measures was larger for women than men. Aerobic exercise also had greater benefits for glucoregulatory function and plasma brain derived neurotrophic factor in women than men. These sex-specific improvements occurred despite the fact that both groups enjoyed comparable improvements in cardiorespiratory fitness. Similar reports of greater benefits of exercise, and physical activity more generally, in women than men have been reported in other meta-analytic and epidemiological studiesReference Colcombe and Kramer ^{93 ,} Reference Middleton, Kirkland and Rockwood ⁹⁴ and may be explained by the fact that the women in these studies tend to be less fit overall (body fat, lipid profiles, cortisol levels) at baseline, and thus have more room for improvement.

Adherence to Mediterranean-style dietary patterns has been associated with a reduced risk of MCI and AD in epidemiological studies.Reference Singh, Parsaik and Mielke ⁹⁵ Few diet intervention studies in MCI populations have been published to date, but so far their results are promising. For example, Bayer-Carter et al Reference Bayer-Carter, Green and Montine ⁹⁶ randomized 49 healthy older adults and 29 adults with amnestic MCI to either a high-saturated fat/high glycemic index (HIGH) diet or a low-saturated fat/low glycemic index (LOW) diet for four weeks. In the MCI group, compared to the HIGH diet, the LOW diet resulted in increased CSF Aβ levels (indicative of improved brain clearance); increased CSF insulin concentrations; and decreased plasma lipids, insulin, and CSF F2-isoprostane concentrations. The beneficial effects of the LOW diet on CSF Aβ were later found to be potentiated in individuals who reported engaging in more high intensity physical activity,Reference Baker, Bayer-Carter and Skinner ⁹⁷ hinting at the likely additive or synergistic effects of multicomponent approaches to healthy lifestyle interventions to increase reserve in people with MCI.

Another approach to increase reserve and everyday functioning in people with MCI is group psychosocial education. These interventions typically teach people practical, everyday memory strategies such as mental imagery and semantic processing to improve encoding of information; teach people about the effects of lifestyle factors such as exercise, diet, and cognitive and social engagement on memory and facilitate adoption of healthier lifestyles; and address coping strategies such as relaxation and preparing for the future.Reference Belleville, Gilbert, Fontaine, Gagnon, Ménard and Gauthier ^{98 –} Reference Troyer, Murphy, Anderson, Moscovitch and Craik ¹⁰² These studies have reported some improvements on objective tests of memory and other cognitive abilitiesReference Belleville, Gilbert, Fontaine, Gagnon, Ménard and Gauthier ^{98 –} Reference Schmitter-Edgecombe and Dyck ¹⁰¹ and improvements in subjective memory,Reference Belleville, Gilbert, Fontaine, Gagnon, Ménard and Gauthier ^{98 ,} Reference Belleville, Hudon and Bier ^{99 ,} Reference Troyer, Murphy, Anderson, Moscovitch and Craik ¹⁰² but due to variations in the quality of these studies (eg, use of an active control group, selection of appropriate outcome measures), the most recent MCI guidelines suggest that clinicians may (versus should) recommend such programs.Reference Petersen, Lopez and Armstrong ¹⁶ More large-scale trials are needed with proper controls to identify the most effective group intervention approaches for MCI.

The MCI guidelinesReference Petersen, Lopez and Armstrong ¹⁶ also highlight the need to educate patients and families about MCI, and suggest that clinicians should counsel patients and families. This type of counseling is common in some of these programs (eg,Reference Troyer, Murphy, Anderson, Moscovitch and Craik ¹⁰² ), but in response to an identified need for more, accessible information, the current author and her colleagues wrote a book in lay language about what MCI is, how it is diagnosed, and how it can be managed.Reference Anderson, Murphy and Troyer ¹⁰³

In addition to these more comprehensive intervention approaches, a number of investigators are discovering the best approaches to memory interventions for MCI. For example, it has been repeatedly shown that people with MCI learn new information best if they are prevented from making errors while learning.Reference Callahan and Anderson ^{104 –} Reference Roberts, Anderson, Guild, Cyr, Jones and Clare ¹⁰⁶ Efforts to train working memory using adaptive approaches, meaning that the task becomes more difficult as individuals improve on the task, have shown improvements in working memory, but limited generalization to other cognitive domains.Reference Carretti, Borella, Fostinelli and Zavagnin ^{107 ,} Reference Vermeij, Claassen, Dautzenberg and Kessels ¹⁰⁸ Likewise, trials of memory recollection training have shown limited generalization.Reference Finn and McDonald ^{109 ,} Reference Jennings, Lopina and Dagenbach ¹¹⁰ These latter efforts indicate that restorative approaches, attempting to retrain specific cognitive processes, may be less effective cognitive rehabilitation approaches than compensatory approaches such as memory strategy training.