Relationship between comprehensive geriatric assessment and amyloid PET in older persons with MCI

Abstract

Background: The association between amyloid deposition and cognitive, behavioral and physical performance in mild cognitive impairment (MCI) due to Alzheimer's disease (AD) has been poorly investigated, especially in older persons.

Methods: We studied the in vivo correlation between the amyloid deposition at Positron Emission Tomography (amyloid-PET) and the presence of memory loss, reduced executive function, neuropsychiatric symptoms and physical performance in older persons with MCI. Amyloid-PET was performed with 18F-flutemetamol and quantitatively analyzed.

Results: We evaluated 48 subjects, 21 men and 27 women. We performed in each patient a comprehensive geriatric assessment (CGA) including Mini Mental State Examination (MMSE), Clock Drawing Test (CDT), Activity Daily Living (ADL), Instrumental Activity of Daily Living (IADL), Neuropsychiatric inventory (NPI) questionnaire, 15 Geriatric Depression Scale (GDS), Short Physical Performance Battery (SPPB) and Hand Grip strength. Then, each patient underwent amyloid-PET. Mean age of the enrolled subjects was 74.6 ± 7.8 years. All of these subjects showed preserved cognitive function at MMSE > 24, while 29 of 48 subjects (61.0%) had altered CDT. Mean NPI score was 6.9 ± 5.9. The mean value of SPPB score was 9.0 ± 2.6, while the average muscle strength of the upper extremities measured by hand grip was 25.6 ± 7.7 Kg. CT/MRI images showed cortical atrophic changes in 26 of the 48 examined subjects (54.0%), while cerebrovascular modifications were present in 31 subjects (64.5%). Pathological burden of amyloid deposits was detected in 25 of 48 (52.0%) patients with a mean value of global z-score of 2.8 (subjects defined as MCI due to AD). After stratifying subjects in subclasses of clinical alterations, more probability of pathological amyloid deposition was found in subjects with impaired CDT and higher NPI score (O.R. = 3.45 [1.01-11.2], p = 0.04), with both impaired CDT and low physical performance (O.R. = 5.80 [1.04-32.2], p = 0.04), with altered CDT and high NPI score (O.R. = 7.98 [1.38-46.0], p = 0.02), and finally in those subjects with altered CDT, high NPI and low physical performance (O.R. = 5.80 [1.05-32.2], p = 0.04).

Conclusion: Our findings support the recent hypothesis that amyloid deposition could be associated with multiple cerebral dysfunction, mainly affecting executive, behavioral and motor abilities.

Keywords: Alzheimer’s disease; Amyloid deposition; MCI; Older persons; Physical performance; Positron emission tomography; motoric-cognitive risk syndrome.

Fig. 1

a, b, c. This figure shows an example of normal (a) and two amyloid pathological PET results (b, c). After considering only subjects with pathological PET examination, it emerges from the mean of the uptake values of 18F-Flutemetamol a widespread and pathological deposition of cerebral amyloid. In the first patient (b) a lower involvement of sensory-motor regions of the right and left (average values of z-score of 3.25 ± 2.44 and 3.01 ± 2.42, respectively), occipital left and right (average values of z-score of 3.83 ± 3.75 and 3.15 ± 3.08, respectively) and right and left medial temporal region which remains the cortical area less involved by amyloid pathology (mean values of z-score of 0.83 ± 1.59 and 0.47 ± 1.60, respectively). In the second patient (c), the amyloid deposition is more abundant probably expression of advanced disease. There is a higher involvement of sensory-motor regions of the right and left (average values of z-score of 9.52 ± 1.01 and 9.45 ± 1.02, respectively), and occipital regions of the right and left (average values of z-score of 13.11 ± 1.10 and 12.30 ± 1.06, respectively) and right and left medial temporal region which remain the cortical area less involved by amyloid pathology (mean values of z-score of 3.56 ± 0.65 and 2.82 ± 0.62, respectively)