Anti-Aging Therapeutics Volume XVI. A4M American Academy

lesions (e.g., brain tumors, strokes, encephalomalacia) on concomitant computed tomography (CT) brain scans, other neurologic disorders affecting brain functioning (e.g., multiple sclerosis, head trauma), serious systemic illnesses affecting cognitive functioning, or serious psychiatric disorders affecting cognitive functioning (e.g., schizophrenia, bipolar disorder, brain damage or injury).

      The study sample was first divided into 2 groups: positive for PET HM (n=43) or PET NM (n=187), as interpreted by visual inspection of PET scans by radiologists. HM subjects were arranged in groups according to brain regions where HM was detected: Group 1 (parietal), Group 2 (parietal + temporal/frontal), Group 3 (frontal), Group 4 (temporal), Group 5 (focal), and Group 6 (none). The HM subjects were further categorized as amnestic single-domain (n=1), amnestic multi-domain (n=19), non-amnestic single-domain (n=7), non-amnestic multi-domain (n=14), or no signs of MCI (n=2). The NM subjects were also categorized as amnestic single-domain (n=3), amnestic multi-domain (n=27), non-amnestic single-domain (n=50), non-amnestic multi-domain (n=88), or no signs of MCI (n=19).

      FDG PET Scans

      The narrative reports from the neuroradiology group were divided into 6 groups of hypometabolism: parietal, parietal plus temporal/frontal, frontal, temporal, focal, or none. The original reading of the neuroradiology group was reconfirmed with visual inspection of the DICOM PET images.

      The PET scans completed by a private neuroradiology group (MedScan) were conducted with either a whole-body or brain-specific high-resolution PET (Siemens/CTI ECAT HR+, with 4.6×4.6×4.2 mm NEMA; National Electrical Manufacturers Association) using FDG. Methodological details for scanning have been published.¹⁸ Prior to PET imaging, a diagnostic quality CT scan of the brain was performed without intravenous contrast, and the patient’s blood glucose level was assessed as being within normal limits. After the CT scan, 14-18 mCi of FDG was administered intravenously. PET scan imaging was performed approximately 50-minutes after the administration of the radioisotope. Forty-seven slices were obtained at approximately 3.3 mm thickness, covering the entire brain parenchyma from the base of the cerebellum to the vertex.

      CDs of the DICOM image data of the PET scans were converted to Analyze format utilizing MRIcro,¹⁸ which also anonymized the images to which blinded IDs were assigned. The analyzed formatted images were then imported to Statistical Parametric Mapping,¹⁹ where they were reviewed to exclude any scans with significant movement artifact, or areas of hypometabolism related to structural brain disorders not evident in the chart review, but observable on CT scan.

      EEG, P300, and Evoked Potentials Data

      The P300 potential was obtained using Lexicor and Cognitrace. Twenty electrodes were used (5 in frontal region, 2 frontal temporal, 3 occipital, 2 temporal, 2 temporal parietal, 3 parietal, and 3 along the central sulcus). The 2 machines were calibrated with repeat scans. Both Lexicor and Cognitrace use auditory stimuli of low and high beeps, and provide an output of latency and amplitude based on preprogrammed baselines based on age. The latency (in milliseconds) and voltage (in microvolts) from the waveform selected for analysis were calculated by the computer algorithm and documented in the patients’ charts. All data were anonymized with confidential IDs matching those of the PET scans.

      Cognitive Tests for MCI

      Data were also collected regarding patients’ memory complaints. Memory complaint data were used to determine whether the patient met clinical criteria for MCI:

      1.The patient is neither normal nor demented;

      2.Evidence of cognitive deterioration indicated by subjective report of decline by self and/or informant in conjunction with objective cognitive deficits, or objectively measured cognitive decline over time;

      3.Activities of daily living are either intact or only minimally impaired (Table 1).²⁰

      Table 1: MCI domain assessment

      *MCI patient checklist

	Domain	Yes	No	For Staff Use – any under 10^th percentile
1	Attention deficits indicated by missing stop signs, jumping the gun, slow response time, or inconsistency in manner of response			TOVA
2	Reaction Time			CNSVS, TOVA
3	Judgment the ability to make good decisions			CNSVS, TOVA
4	Learning Ability understanding concepts or instructions and ability to reason			WMS, CNSVS, WAIS
5	Delayed Recall free (without assistance), cued (with assistance of stimulus or prompt), or serial (recall items/events in order in which they were learnt), ability to retrieve information a given time period after which it was learnt			WMS, CNSVS
6	Linguistic Function ability to communicate effectively			MMSE
7	Verbal IQ ability to analyze information and solve language based problems of a literary, logical, or social type; understanding relationships between language concepts and performing language analogies and comparisons			WAIS