Unawareness of Memory Deficits Depending on Cerebral Perfusion Pattern in Mild Cognitive Impairment

To the Editor: Although patients with Alzheimer's disease (AD) are often unaware of their cognitive or functional impairment, few studies have examined whether patients with mild cognitive impairment (MCI) are aware of their impairment.1, 2 MCI is considered to refer to a transitional zone between normal cognitive function and dementia.3 It may represent a complex heterogenous condition. When subjects with MCI are followed over time, some progress to dementia, especially AD, but some are stable or even recover. Indeed, neuroimaging studies have showed that patients with MCI had a variety of cerebral perfusion patterns, from normal perfusion to a similar hypoperfusion pattern of AD. The correlation between the level of awareness of memory deficits and cerebral perfusion pattern in patients with MCI was investigated. Forty-three consecutive outpatients with amnestic MCI, defined using an operationalization of criteria previously published3 were enrolled. Patients with a known or suspected cause of memory impairment (e.g., depression, anxiety disorder, alcohol abuse) were not classified as having MCI so as to include only patients with amnestic MCI. All patients underwent single photon emission computed tomography (SPECT) studies with 222MBq of N-isopropyl-p-(123I) iodoamphetamine. SPECT data were analyzed using three-dimensional stereotactic surface projections,4 and z-score on a pixel-by-pixel basis was calculated. The detailed SPECT procedure and data analysis are described in detail elsewhere.5 Qualitative analysis on z-score image was blindly performed by consensus between two experienced observers. An image was defined as AD pattern if cerebral perfusion was reduced in bilateral parietotemporal or posterior cingulate areas with relative sparing of the sensorimotor cortex, occipital cortex, and cerebellum. Each image was defined as AD pattern or non-AD pattern. The unawareness of memory impairment was evaluated using a standardized questionnaire system based on the Everyday Memory Checklist (EMC) of Wilson et al.6 The EMC was translated into Japanese and slightly modified to fit Japanese culture and has been used to assess unawareness of memory impairment.7, 8 The EMC consisted of 13 questions concerning areas of daily life; each answer was rated as never (0 points), sometimes (1 point), usually (2 points), or always (3 points). Thus, higher scores indicate more-severe impairments. The EMC scores for the patient's own rating, the caregivers' rating, and the unawareness score, defined as the difference between these (caregiver rating–patient rating), were analyzed. The reliability and validation of the version of the EMC in amnestic patients, including AD, have been demonstrated to be acceptable.7 Values are expressed as means±standard deviation. Statistical analysis was performed using the Student t test, chi-square test, and Mann-Whitney U-test. Twenty-five patients had AD pattern, and 18 had non-AD pattern based on the SPECT images. Table 1 shows demographic features and results of EMC scores. There were no significant differences in age, sex, education, duration of symptoms, Mini-Mental State Examination score, Logical Memory subscore, of Wechsler Memory Scale-Revised and Alzheimer's Disease Assessment Scale—Cognitive Subscale (Japanese version) between AD pattern and non-AD pattern groups. Between-group comparison showed comparable EMC self-rating scores in AD pattern and non-AD pattern groups. In contrast, EMC scores in caregivers were significantly higher in the AD pattern group than in the non-AD pattern group (P<.01). Therefore, the unawareness score was significantly higher in the AD pattern group than in the non-AD pattern group, indicating impaired awareness in the AD pattern group (P<.01). The unawareness score found in the AD pattern group was similar to that in patients with mild AD previously reported.8 Although the unawareness score may vary depending on the type of caregiver,8 no differences were found in the relationship between caregiver and patient in the two groups (spouse to others; 15:10 of the AD pattern group versus 11:7 of the non-AD pattern group). Reflecting the heterogeneity of MCI, the level of awareness of memory deficits may be variable. Although several clinical and neuropsychological parameters may be associated with unawareness, it was found that patients with posteromedial hypoperfusion had impaired awareness of memory deficits. Posteromedial hypoperfusion suggests the presence of underlying AD pathology and prediction of conversion to AD.9 Because a previous study showed that lack of awareness of functional deficits may be an early diagnostic marker for AD,10 impaired awareness of memory deficits may be predictive of a future diagnosis of AD. A longitudinal study will be needed to determine whether patients with impaired awareness of memory deficits are more likely to develop AD. Financial Disclosure: The authors state that they have no financial disclosures to declare. There are no conflicts of interest in this letter. Author Contributions: Haruo Hanyu: study concept and design, acquisition of subjects and data, analysis and interpretation of data, and preparation of manuscript. Hirofumi Sakurai and Toshihiko Iwamoto: acquisition of subjects and data and analysis. Kentaro Hirao and Soichiro Shimizu: analysis and interpretation of data. Sponsor's Role: None.